Fungal Endophytes: A Potential Source of Antibacterial Compounds

Abstract

Antibiotic resistance is becoming a burning issue due to the frequent use of antibiotics for curing common bacterial infections, indicating that we are running out of effective antibiotics. This has been more obvious during recent corona pandemics. Similarly, enhancement of antimicrobial resistance (AMR) is strengthening the pathogenicity and virulence of infectious microbes. Endophytes have shown expression of various new many bioactive compounds with significant biological activities. Specifically, in endophytic fungi, bioactive metabolites with unique skeletons have been identified which could be helpful in the prevention of increasing antimicrobial resistance. The major classes of metabolites reported include anthraquinone, sesquiterpenoid, chromone, xanthone, phenols, quinones, quinolone, piperazine, coumarins and cyclic peptides. In the present review, we reported 451 bioactive metabolites isolated from various groups of endophytic fungi from January 2015 to April 2021 along with their antibacterial profiling, chemical structures and mode of action. In addition, we also discussed various methods including epigenetic modifications, co-culture, and OSMAC to induce silent gene clusters for the production of noble bioactive compounds in endophytic fungi.

1. Introduction

Over the decades since the discovery of the first antibiotics, resistance to those has been a curse that is being dragged along with every discovery of new antibiotics. This has kept all scientists, professionals, and clinical specialists working on antibiotics on their toes. The quest for new antibiotics scaffolds and repurposing of existing molecules has been persistent for the past nine decades. Getting a new and right scaffold is a herculean task, especially with the least ability to induce mutations in the target bacteria. As examined in some of the earlier reviews [1,2] there are several ways of getting new scaffolds and classes of antimicrobial bioactive compounds. In the domain of natural products, one of the most demonstrated ways is studying less explored species and genera of microbes [3,4,5]. Investigating unexplored ecological units on the globe synergizes with the concept of investigating the least or not explored species of microbes.

In the current review, we present the latest ways of exploring the credentials of such microbial sources, especially endophytic fungi, as a main stream of novel antimicrobial scaffolds. Bioactive compounds are mainly responsible for the activity profiles displayed by endophytic fungi. These metabolites belong to a wide range of scaffolds such as alkaloids, benzopyranones, chinones, peptides, phenols, quinones, flavonoids, steroids, terpenoids, tetralones, xanthones, and others. Moreover, they, in the pure form, have demonstrated abundant biological activities, including antibacterial, antifungal, anticancer, antiviral, antioxidant, immunosuppressant, anti-inflammatory, and antiparasitic properties [6,7,8,9,10,11,12,13,14,15]. Even though there are a few specialized reviews on the bioactive compounds from fungi, actinomycetes and other microbes [16,17], the amount of work done in the area is quite versatile, tenacious and significant. There is a need to comprehend these topics periodically to have its effective output for future research keeping in mind the probability of success of any newly discovered bioactive compound in clinical studies has been 0.01 to 1 % based on therapeutic area and type of scaffold. This demands that the base of such scaffolds in the ladder of clinical development should be wider. This width can be increased by exploring such less-tapped resources, the endophytic fungi.

In our previous review, we have covered antibacterials reported from endophytic fungi up to 2014 [1]. This review describes some bioactive molecules isolated from 2015 onwards to early 2021 from various endophytic fungi from terrestrial plants and designated as antibacterials. The antibacterial activity against various pathogenic organisms is listed in Table 1.

2. Antibacterials from Various Class of Endophytic Fungi

2.1. Ascomycetes

Ascomycetes are the fungi characterized by the formation of ascospores and some of the genera belonging to this class are known to produce chemically diverse metabolites. The important genera include Diaporthe, Xylaria, Chaetomium, Talaromyces, and Paraphaeosphaeria and are known to produce terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds. Here we report the antibacterial from ascomycetes.

2.1.1. Diaporthe (Asexual State: Phomopsis)

The genus Diaporthe (asexual state: Phomopsis) has been thoroughly investigated for secondary metabolites that have various pathogenic, endophytic and saprobic species of temperate and tropical habitats. Two natural bisanthraquinone, (+)-1,1′-bislunatin (bis) (1) and (+)-2,2′-epicytoskyrin A (epi) (2, Figure 1), were extracted from endophytic fungi, Diaporthe sp. GNBP-10 is associated with plant Uncaria gambir. Compounds (bis)-(1) and (epi)-(2) showed promising anti-tubercular activity, against Mycobacterium tuberculosis strains H37Rv (Mtb H37Rv) with MIC values of 0.422 and 0.844 μM, respectively. Both compounds have the ability to combat nutrient-starvation and biofilms of the Mtb model with relatively moderate activity in bacterial reduction with between 1–2 fold log reduction. Both compounds could reduce the number of Mtb infected into macrophages with 2-fold log reduction. The in-silico results via a docking study show that both compounds have a good affinity with pantothenate kinase (PanK) enzyme with a Glide score of −8.427 kcal/mol and −7.481 kcal/mol for the epi and bis compounds, respectively [18].

An endophytic fungus, Diaporthe sp. GDG-118, associated with Sophora tonkinensis collected from Hechi City (China) yielded a new compound 21-acetoxycytochalasin J3 (3, Figure 1) and inhibited the pathogens Bacillus anthraci and E. coli at 12.5 μg/mL concentration (6 mm sterile filter paper discs were impregnated with 20 µL (50 µg) of each compound) [19].

Two novel naphthalene derivatives, 1-(3-hydroxy-1-(hydroxymethyl)-2-methoxy-6-methylnaphthalen-7-yl) propan-2-one (4) and 1-(3-hydroxy-1-(hydroxymethyl)-6-methyl-naphthalen-7-yl)propan-2-one (5, Figure 1), were obtained from the Phomopsis fukushii. Compounds 4 and 5 displayed poor anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity, with zones of inhibition of 10.2 and 11.3 mm, respectively (6 mm sterile filter paper discs were impregnated with 20 µL (50 µg) of each compound) [20].

Earlier Phomopsis fukushii (Diaporthe fukushii) isolated from the rhizome of Paris polyphylla var. yunnanensis was the source of three new compounds namely 3-hydroxy-1-(1,8- dihydroxy-3,6-dimethoxynaphthalen-2-yl)propan-1-one (6), 3-hydroxy-1-(1,3,8-trihydroxy-6-methoxynaphthalen-2-yl)propan-1-one (7) and 3-hydroxy-1-(1,8-dihydroxy3,5-dimethoxy naphthalen-2-yl) propan-1-one (8, Figure 1). Compounds 6–8 exhibited anti-MRSA-ZR11 activity, with MIC values of 8, 4, and 4 µg/mL, respectively [21]. Later two new di-Ph ethers, 1-[2-methoxy-4-(3-methoxy-5-methylphenoxy)-6-methylphenyl]-ethanone (9) and 1-[4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6-methylphenyl]-ethanone (10, Figure 1), were also purified from the same fungus. Compounds 9–10 exhibited anti-MRSA activity with good inhibition (zones of 13.8 and 14.6 mm, respectively) [22].

Three new di-Ph ethers, 4-(3-methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (11), 4-(3-hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (12) and 4-(3-methoxy-5-methylphenoxy)-2-(3-hydroxypropyl)-6-methylphenol (13, Figure 1) were purified from Phomopsis fukushii associated with the rhizome of Paris polyphylla var. yunnanensis. Compounds 11–13, exhibited potent anti-MRSA activity, with 20.2, 17.9 and 15.2 mm inhibition zones, respectively, when tested at 50 µg concentration in 6 mm discs [23].

Phomopsis fukushii isolated from the rhizome of Paris polyphylla var. yunnanensis yielded three new isopentylated diphenyl ethers, 1-(4-(3-methoxy-5-methylphenoxy)-2-methoxy-6-methylphenyl)-3-methylbut-3-en-2-one (14), 1-(4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6-methylphenyl)-3-methylbut-3-en-2-one (15) and 1-(4-(3-hydroxy-5-(hydroxymethyl) phenoxy)-2-methoxy-6-methylphenyl)-3-methylbut-3-en-2-one (16, Figure 1). Compounds 14–16 displayed anti-MRSA activity with 21.8, 16.8 and 15.6 mm inhibition zones, respectively (50 µg/6 mm disc) [24].

Two new anthraquinones, 3-hydroxy-6-hydroxymethyl-2,5-dimethylanthraquinone (17) and 6-hydroxymethyl-3-methoxy-2,5-dimethylanthraquinone (18, Figure 1), were purified from the endophytic fungus Phomopsis sp. and displayed good anti-MRSA activity with inhibition zone diameters (IZDs) of 14.2 and 14.8 mm, respectively [25].

A new dihydroisocoumarin derivative diaporone A (19, Figure 1), was purified from Diaporthe sp. an endophyte of Pteroceltis tatarinowii. Compound 19 showed MIC at 66.7 μM against Bacillus subtilis [26].

A pair of new phenolic bisabolane-type sesquiterpenoid enantiomers (±)-phomoterpenes A and B [(±)-1] (20) along with two new isocoumarins, phomoisocoumarins C-D (21–22, Figure 1) were purified from an endophytic fungus Phomopsis prunorum (F4-3). Compounds (+)-1 (20 and 22) exhibited average antimicrobial activity against Pseudomonas syringae pv. lachrymans with MIC values of 15.6 μg/mL, and compounds (−)-1 (20 and 21) displayed poor activity with MICs of 31.2 μg/mL each. Compounds (−)-1, (+)-1, (20, 21, 22) showed antibacterial activity against Xanthomonas citri pv. phaseoli var. fuscans with MIC values of 31.2, 62.4, 31.2, and 31.2 μg/mL, respectively [27].

The fungus Diporthe vochysiae LGMF1583 isolated from Vochysia divergens yielded two new carboxamides, vochysiamides A (23), and B (24, Figure 2). Compound 24 inhibited Klebsiella pneumoniae carbapenemase-producing (KPC), MSSA, and MRSA with MIC of 0.08, 1.0, and 1.0 µg/mL, respectively, and compound 23 was active against KPC with a MIC of 1.0 μg/mL. KPC is of public health concern due to the presence of antimicrobial resistance carbapenemases [28].

An endophyte Phomopsis asparagi obtained from the rhizome of Paris polyphylla var. yunnanensis was the source of two new di-Ph ethers, 4-(3-methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)- 6-(hydroxymethyl)phenol (25), and 4-(3-hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-(hydroxymethyl)phenol (26, Figure 2). Compounds 25 and 26 exhibited potent anti-MRSA activity with 10.8 and 11.4 mm inhibition zones, respectively [29].

Two new naphthalene derivatives, 5-methoxy-2-methyl-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (27) and 2-(hydroxymethyl)-5-methoxy-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (28, Figure 2), were characterized from Phomopsis sp., an endophyte of Paris polyphylla var. yunnanensis. Compounds 27 and 28 displayed potent antibacterial activity with 14.5 and 15.2 mm zones of inhibition, respectively, against MRSA [30].

The endophytic fungus Diaporthe terebinthifolii LGMF907 associated with the plant Schinus terebinthifolius yielded diaporthin (29) and orthosporin (30, Figure 2). Compound 29 displayed antimicrobial activity against various pathogens like E. coli, Micrococcus luteus, MRSA, and S. aureus with 1.73, 2.47, 9.50, and 9.0 mm zones of inhibition, respectively at 100 μg/disk concentration. Compound 30 inhibited E. coli, M. luteus, MRSA, and S. aureus with 1.03, 1.53, 9.0 and 9.33 mm zones of inhibition, respectively, when tested at 100 μg/disk [31].

A pyrimidine iminomethylfuran derivative, (2Z)-2-(1,4-dihydro-2-hydroxy-1-((E)-2-mercapto-1-(methylimino)ethyl)pyrimidine-4-ylimino)-1-(4,5-dihydro-5-methylfuran-3-yl)-3-methylbutane-1-one (31, Figure 2) was extracted from Phomopsis/Diaporthe sp. GJJM 16 is associated with Vitex negundo and inhibited S. aureus, and P. aeroginosa with MICs of 1.25 μg/mL each [32].

Phomopsis sp. PSU-H188 associated with Hevea brasiliensis, yielded the known compounds diaporthalasin (32), cytosporones B (33) and cytosporones D (34, Figure 2). Compound 32, displayed antibacterial activity against S. aureus and MRSA with equal MIC values of 4 μg/mL, but compound 33 inhibited S. aureus and MRSA with MIC values of 32 and 16 μg/mL, respectively. Compound 34 also inhibited S. aureus and MRSA with MIC values at higher concentrations of 64 and 32 μg/mL, respectively [33].

An endophyte, Diaporthe terebinthifolii GG3F6, associated with Glycyrrhiza glabra yielded two new hydroxylated unsaturated fatty acids namely diapolic acid A–B (35–36) and the known molecules xylarolide (37, Figure 2) and phomolide G (38, Figure 3). Compounds 35–38 inhibited Yersinia enterocolitica with an IC₅₀ values of 78.4, 73.4, 72.1 and 69.2 μM, respectively [34].

The compounds phomosine A (39), and phomosine C (40, Figure 3), were obtained from Diaporthe sp. F2934 from Siparuna gesnerioides. Compound 39 was found to be active against Bordetella bronchiseptica, Enterococcus faecalis, Enterococcus cloacae, S. aureus, and Streptococcus oralis with 10, 10, 10, 12 and 9 mm inhibition zones at 4 µg/mL concentration, respectively. Compound 40 inhibited S. aureus, M. luteus, S. oralis, E. faecalis, E. cloacae, and B. bronchiseptica, with 9, 6, 8, 8, 8 and 9 mm inhibition zones at 4 µg/mL concentration, respectively [35].

Known cytochalasins 18-methoxycytochalasin J (41), cytochalasins H (42), J (43) and alternariol (44, Figure 3) were extracted from Phomopsis sp., residing inside Garcinia kola nuts. Compounds 41–44 were found to be active against Shigella flexneri (MIC, 128 μg/mL each). Compounds 41 and 42 showed activity against S. aureus with MIC values of 128 and 256 μg/mL, respectively [36].

The fungal culture Diaporthe sp. LG23, an endophyte of Mahonia fortune, yielded some new lanostanoids, 19-nor-lanosta-5(10),6,8,24-tetraene-1α,3β,12β,22S-tetraol (45), 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (46), and chaxine C (47, Figure 3). Compound 45 was found to be active against S. aureus, E. coli, B. subtilis, Pseudomonas aeruginosa, and Streptococcus pyogenes, with MIC values of 5.0, 5.0, 2.0, 2.0 and 0.1 µg/mL, respectively. Compounds 46 and 47 were active against B. subtilis with MIC values of 5.0 µg/mL each [37].

The known compound, pyrrolocin A (48, Figure 3), was purified from Diaporthales sp. E6927E isolated from Ficus sphenophyllum. Pyrrolocin A (48) displayed inhibition against S. aureus and E. faecalis with MICs of 4 and 5 µg/mL, respectively [38].

2.1.2. Xylaria

The genus Xylaria comprises various endophytic species associated with both vascular and nonvascular plants. For example, ellisiiamide A (49, Figure 3) was isolated from Xylaria ellisii from Vaccinium angustifolium and was chemically characterized using 1D and 2D NMR, HRMS/MS data. It showed modest inhibitory activity against E. coli (MIC, 100 μg/mL) [39].

Xylareremophil (50), a new eremophilane sesquiterpene, along with the already reported eremophilanes mairetolides B (51) and G (52, Figure 3) were extracted from Xylaria sp. GDG-102 residing inside S. tonkinensis. Compound 50 displayed moderate activity against Proteus vulgaris and Micrococcus luteus (MIC, of 25 μg/mL each). Compound 51 was found to be active against M. luteus, with a MIC value of 50 μg/mL. Compound 52 inhibited P. vulgaris with a MIC value of 25 μg/mL and M. luteus with a MIC value of 50 μg/mL. Compounds 50–52 also displayed inhibition of B. subtilis and Micrococcus lysodeikticus with MIC values of 100 μg/mL, respectively [40].

A new compound, 6-heptanoyl-4-methoxy-2H-pyran-2-one (53, Figure 3), was purified from Xylaria sp. (GDG-102) an endophyte of S. tonkinensis and displayed antibacterial activity against E. coli as well as S. aureus (MIC, 50 μg/mL) [41].

The phthalide derivative xylarphthalide A (54) and known compounds (−)-5-carboxylmellein (55, Figure 3) and (−)-5-methylmellein (56, Figure 4) were extracted from Xylaria sp. (GDG-102) associated with S. tonkinensis. Compound 54 inhibited Bacillus anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, Shigella dysenteriae and Salmonella paratyphi, with the MICs of 50, 25, 12.5, 25, 12.5, 25 and 25 μg/mL, respectively. Compound 55 showed antibacterial activity with MIC of values of 25, 25, 12.5, 25, 25, 25 and 25 μg/mL against B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi, respectively. Compound 56 displayed antibacterial activity with MIC values of 25, 12.5, 12.5, 25, 25, and 50 μg/mL against B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi, respectively [42].

A novel compound 3,7-dimethyl-9-(-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)nona-1,6-dien-3-ol (57), and previously reported compound nalgiovensin (58, Figure 4) were purified from Xylaria sp., associated with Taxus mairei. Compound 57 exhibited strong inhibition against B. subtilis (48.1%), B. pumilus (31.6%) and S. aureus (47.1%). Compound 58 exhibited broad inhibition against S. aureus (42.1%), B. subtilis (36.8%), B. pumilus (47.1%) and E. coli (41.2%) [43].

2.1.3. Chaetomium

The genus Chaetomium has been included among the genera producing various bioactive compounds and more than 200 secondary metabolites belonging to diverse structural types such as anthraquinones, azaphilones, chaetoglobosins, chromones, depsidones, epipolythiodioxopiperazines, terpenoids, and steroids and xanthones have beenrecorded, making it a rich source of novel bioactive metabolites. Most of these fungal metabolites exhibited antitumor, cytotoxic, antimalarial, enzyme inhibitory, antibiotic, and other activities [44]. Here we report the antibacterial compounds isolated from the genus Chaetomium.

A new xanthoquinodin B9 (59), along with previously reported two xanthoquinodins, xanthoquinodin A1 (60) and xanthoquinodin A3 (61), and three epipolythio- dioxopiperazines, chetomin (62), chaetocochin C (63) and dethiotetra(methylthio)chetomin (64, Figure 4), were obtained from C. globosum 7s-1, associated with Rhapis cochinchinensis. Xanthoquinodins 59–61 displayed potent antibacterial activity, with MIC values of 0.87, 0.44 and 0.22 μM against B. cereus, respectively. Compounds 59–61 were also found active against S. aureus and MRSA (MICs in the range of 0.87 to 1.75 μM). Epipolythiodioxopiperazines 62–64 exhibited potent activity against B. cereus, S. aureus, and MRSA (MICs in the range of 0.02 pM to 10.81 mM). Compound 62 showed the highest activity towards B. cereus, S. aureus and MRSA (MICs of 0.35 μM, 10.74 and 0.02 pM). Compounds 59–64 showed poor activity against E. coli, P. aeruginosa, and Salmonella typhimurium (MICs of 45.06 to >223.72 μM). Epipolythiodioxopiperazines 62–64 showed activity against Mycobacterium tuberculosis with MICs of 0.55, 4.06 and 8.11 μM, respectively [45].

Known compounds chaetocochin C (63), chetomin A (65) and chetomin (62, Figure 4) were extracted from Chaetomium sp. SYP-F7950 residing inside Panax notoginseng. Compounds 62, 63 and 65 displayed potent activity against B. subtilis, S. aureus, and Enterococcus faecium, with MIC values ranging from 0.12 to 19.3 μg/mL. The length of B. subtilis was increased up to 1.8-fold after treatment with compounds 62, 63 and 65. These compounds also showed good interactions with the filamentous temperature-sensitive protein Z (FtsZ) of B. subtilis in an in silico molecular docking study. These results revealed that inhibition of pathogenic B. subtilis could be achieved by combination with FtsZ and inhibition of cell division [46].

Compounds differanisole A (66), 2,6-dichloro-4-propylphenol (67) and 4,5-dimethylresorcinol (68, Figure 4), were purified from Chaetomium sp. HQ-1, isolated from Astragalus chinensis. Compounds 66–68 displayed average activity against Listeria monocytogenes, S. aureus, and MRSA (MICs ranging from 16 to 128 μg/mL). Compound 66 showed a MIC of 16 μg/mL for L. monocytogenes and a MIC of 128 μg/mL for S. aureus and MRSA. Compounds 67 and 68 could suppress the growth of L. monocytogenes with MICs of 64 and 32 μg/mL, respectively [47].

A novel cytochalasan, chamiside A (69, Figure 4), was obtained from Chaetomium nigricolor F5, an endophytic fungus associated with Mahonia fortune collected from Qingdao (China) and showed inhibition of S. aureus with a MIC of 25 μg/mL [48].

A known compound, equisetin (70, Figure 4), was purified from C. globosum of Salvia miltiorrhiza. Compound 70 displayed activity against multidrug-resistant E. faecalis, E. faecium, S. aureus, and S. epidermidis with MIC values of 3.13, 6.25, 3.13, and 6.25 μg/mL, respectively [49].

Chaetomium sp. Eef-10, from Eucalyptus exserta yielded a new depsidone mollicellin O (71), along with the known compounds mollicellin H (72) and mollicellin I (73, Figure 5). Mollicellin H (72) displayed potent activity against S. aureus and S. aureus N50, with IC₅₀ values of 5.14 and 6.21 μg/mL, respectively. Mollicellin O (71) exhibited antibacterial activities against S. aureus and S. aureus N50, with IC₅₀ values of 79.44 and 76.35 μg/mL, respectively, while mollicellin I (73) exhibited activity against S. aureus and S. aureus N50 with IC₅₀ values of 70.14 and 63.15 μg/mL, respectively [50].

A new compound, 6-formamidochetomin (74, Figure 5) was isolated from Chaetomium sp. M336 an endophyte of Huperzia serrata. Compound 74 inhibited E. coli, S. aureus, S. typhimurium and E. faecalis with MIC values of 0.78 μg/mL [51].

Two known cytochalasans, chaetoglobosin A (75) and C (76, Figure 5), were purified from Chaetomium globosum, an endophyte of Nymphaea nouchali. Compound 75 inhibited B. subtilis, S. aureus, and MRSA with MIC values of 16, 32 and 32 μg/mL, respectively, and the MIC values for compound 76 were >64 μg/mL for all the microorganisms tested [52].

2.1.4. Talaromyces

An endophytic fungus Talaromyces pinophilus XL-1193 residing inside the plant Salvia miltiorrhiza yielded a new polyene, pinophol A (77, Figure 5). Pinophol A (77) exhibited low activity against Bacterium paratyphosum B with a MIC value of 50 μg/mL [53].

The compounds talaroconvolutin A (78) and talaroconvolutin B (79, Figure 5), were discovered in Talaromyces purpureogenus XL-25, an endophyte associated with Panax notoginseng. Compound 78 showed pronounced activity against B. subtilis (MIC, 1.56 μM). Compound 79 had a certain inhibitory activity against Micrococcus lysodeikticus (MIC = 0.73 μM) and Vibrio parahaemolyticus (MIC = 0.18 μM) [54].

A drimane sesquiterpenoid (1S,5S,7S,10S)-dihydroxyconfertifolin (80, Figure 5) was purified from Talaromyces purpureogenus residing inside the plant Panax notoginseng. Compound 80 inhibited E. coli with a MIC value of 25 μM/L [55].

A novel polyketide, talafun (81), and a new compound, N-(2′-hydroxy-3′-octadecenoyl)-9-methyl-4,8-sphingadienin (82, Figure 5), were purified from Talaromyces funiculosus -Salicorn 58 together with some previously reported compounds, chrodrimanin A (83), and chrodrimanin B (84, Figure 6). Compound 81 exhibited potent activity against E. coli (MIC, 18 μM) but poor activity toward S. aureus (MIC, 93 μM). Compound 82 was found to be active against Mycobacterium smegmatis, S. aureus, Micrococcus tetragenus, and E. coli, with MIC values of 85, 90, 24, and 68, 93 μM, respectively. Compound 83 inhibited S. aureus, M. tetragenus, Mycobacterium phlei, and E. coli (MICs of 67, 28, 47, and 26 μM). However, compound 84 showed only moderate activity against E. coli with a MIC of 43 μM [56].

Alkaloids 85–90 (Figure 6), were extracted from Talaromyces sp. LGT-2, from Tripterygium wilfordii. Compounds 85–90 inhibited E. coli, P. aeruginosa, S. aureus, Bacillus licheniformis, and Streptococcus pneumoniae, with MIC values in the range of 0.125 to 1.0 50 μg/mL [57].

2.1.5. Minor Taxa of the Ascomycetes

The known compound euphorbol (91, Figure 6) was isolated from Rhytidhysteron sp. BZM-9, an endophyte isolated from the leaves of Leptospermum brachyandrum. Compound 91 displayed weak antibacterial activity against MRSA, with a MIC value of 62.5 μg/mL (positive control vancomycin MIC 1.25 μg/mL) [58].

A new natural product, stagonosporopsin C (92, Figure 6) was purified from an endophytic fungus, Stagonosporopsis oculihominis, isolated from Dendrobium huoshanense. Stagonosporopsin C (92) exhibited moderate inhibitory activity against S. aureus sub sp. aureus ATCC29213 with a MIC₅₀ value of 41.3 μM (positive control penicillin G, MIC₅₀ value 1.963 μM) [59].

Two new compounds eutyscoparols H-I (93, 94) together with the related known ones tetrahydroauroglaucin (95) and flavoglaucin (96, Figure 6), were isolated from the endophytic fungus Eutypella scoparia SCBG-8. Compounds 93–96 displayed growth inhibition against S. aureus and MRSA, with MIC values ranging from 1.25 to 6.25 μg/mL [60].

A new sesquiterpene eutyscoparin G (97, Figure 6) was purified from an endophytic fungus Eutypella scoparia SCBG-8 isolated from leaves of Leptospermum brachyandrum from the South China Botanical Garden (SCBG, Chinese Academy of Sciences, Guangzhou, China). Compound 97 exhibited antibacterial activity against S. aureus and MRSA with MIC values of 6.3 μg/mL [61].

Two new helvolic acid derivatives named sarocladilactone A (98), sarocladilactone B (99), along with the previously reported compounds helvolic acid (100), helvolinic acid (101), 6-desacetoxyhelvolic acid (102, Figure 6), and 1,2-dihydrohelvolic acid (103, Figure 7), were isolated from Sarocladium oryzae DX-THL3, associated with leaves of Oryza rufipogon Griff. Compounds 98–103 showed antibacterial activity against S. aureus with MIC values of 64, 4, 8, 1, 4 and 16 μg/mL, respectively (positive control tobramycin MIC 1 μg/mL), while compound 101 also showed antibacterial activity against B. subtilis with a MIC value of 64 μg/mL (positive control tobramycin, MIC 64 μg/mL). Compounds 98, 101, 103, showed some potent antibacterial activity against E. coli with MIC 64 μg/mL [62].

The diketopiperazine cyclo(L-Pro-L-Phe) (104, Figure 7), was purified from Paraphaeosphaeria sporulosa, associated with Fragaria x ananassa. Compound 104 displayed activity against Salmonella strains, S1 and S2, with IC₅₀ values of 7.2 and 7.9 μg/mL and MICs of 71.3 and 78.6 μg/mL, respectively [63].

A fungal culture of Aplosporella javeedii isolated from Orychophragmus violaceus was the source of terpestacin (105) fusaproliferin (106), 6,7,9,10-tetrahydromutolide (107) and mutolide (108, Figure 7). Compounds 105, 106, 108 showed poor activities against M. tuberculosis H37Rv and compound 107 against S. aureus, respectively, with MICs of 100 μM [64].

A new chlamydosporol derivative pleospyrone E (109, Figure 7), was extracted from Pleosporales sp. Sigrf05, residing inside the tuberous roots of Siraitia grosvenorii. Compound 109 exhibited weak inhibition against Agrobacterium tumefaciens, B. subtilis, R. solanacearum, and X. vesicatoria with the same MIC value of 100.0 µM [65].

New polyketides aplojaveediins A and F (110, 111, Figure 7) were purified from the Aplosporella javeedii associated with the Orychophragmus violaceus. Compound 110 exhibited average activity against the sensitive Staphylococcus aureus strain ATCC 29213, the methicillin-resistant and vancomycin-intermediate sensitive (MRSA/VISA) S. aureus strain ATCC 700699 and B. subtilis (ATCC 169) with MICs of 50, 50 and 25 μM, respectively. Compound 111 also exhibited moderate inhibition against S. aureus ATCC 29213 and ATCC 700699 with MICs of 25 and 50 μM, respectively [66].

A new chromone, lawsozaheer (112, Figure 7), was isolated from Paecilomyces variotii from Lawsonia alba. Compound 112 showed activity against S. aureus (NCTC 6571) with 84.26% inhibition at 150 μg/mL [67].

A known polyketide, setosol (113, Figure 7), was extracted from an endophytic fungus Preussia isomera in Panax notoginseng from Wenshan, by using an OSMAC strategy. Compound 113 displayed potent activity against multidrug-resistant E. faecium, methicinllin-resistant S. aureus and multidrug-resistant E. faecalis with MIC values of 25 μg/mL [68].

A pair of enantiomeric norsesquiterpenoids, (+)- (114) and (−)-preuisolactone A (115, Figure 7) featuring an unprecedented tricyclo[4.4.01,6.02,8]decane carbon scaffold were isolated from Preussia isomera. XL-1326, obtained from the stems of Panax notoginseng. Compounds (+)-I and (−)-II are 2 rare naturally occurring sesquiterpenoidal enantiomers. Compounds 114 and 115 exhibited potent antibacterial activity against Micrococcus luteus and B. megaterium with MIC values of 10.2 and 163.4 μM, respectively [69].

A new α-pyrone derivative, udagawanone A (116, Figure 7) was isolated from Neurospora udagawae associated with Quercus macranthera, and displayed moderate inhibition against S. aureus (MIC = 66 μg/mL) [70].

Five chromone derivatives, including 2,6-dimethyl-5-methoxy-7-hydroxychromone (117), 6-hydroxymethyleugenin (118), 6-methoxymethyleugenin (119), and isoeugenitol (120), and isocoumarin congeners, 8-hydroxy-6-methoxy-3-methylisocoumarin (121, Figure 7) and diaporthin (29), were purified from Xylomelasma sp. Samif07, an endophyte of Salvia miltiorrhiza. Compound 120 showed good activity against M. tuberculosis (MIC 10.31 μg/mL). Compounds 29, 117–121 displayed inhibitory activities against B. subtilis, Staphylococcus haemolyticus, A. tumefaciens, Erwinia carotovora, and X. vesicatoria (with MICs ranging from 25 ~ 100 μg/mL). Compounds 117 and 29 showed inhibition against only E. carotovora (MIC, 100 μg/mL), and B. subtilis (MIC, 50 μg/mL), respectively. Compounds 118, 119, 29 were found active against S. haemolyticus and E. carotovora (MIC of 75 μg/mL), whereas compound 121 exhibited stronger inhibition against B. subtilis, A. tumefaciens, and X. vesicatoria, with MICs of 25, 75, and 25 μg/mL, respectively [71].

The compound (4S,5S,6S)-5,6-epoxy-4-hydroxy-3-methoxy-5-methylcyclohex-2-en-1-one (122, Figure 7) was purified from Amphirosellinia nigrospora JS-1675, an endophytic fungus isolated from the stem tissue of Pteris cretica. Compound 122 showed high to moderate in vitro antibacterial activity, with MIC values ranging between 31.2 and 500 µg mL⁻¹ against Pectobacterium carotovorum subsp. Carotovorum, Agrobacterium konjaci, Burkholderia glumae, Clavibacter michiganensis subsp. michiganensis, A. tumefaciens, Pectobacterium chrysanthemi, R. solanacearum, Acidovorax avenae subsp. cattlyae, Xanthomonas arboricola pv. pruni, X. euvesicatoria, X. axonopodis pv. Citri, X. oryzae pv. oryzae [72].

Two new alkylated furan derivatives, 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-ol (123) and 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-carbonate (124, Figure 7), were isolated from Emericella sp. XL029, an endophyte of Panax notoginseng. Compounds 123, 124 inhibited B. subtilis, B. cereus, S. aureus, B. paratyphosum B, S. typhi, P. aeruginosa, E. coli, and E. aerogenes with MIC values ranging from 6.3 to 50 μg/mL [73].

Four new compounds, 14-hydroxytajixanthone (125), 14-hydroxyltajixanthone hydrate (126, Figure 7), 14-hydroxy-15-chlorotajixanthone hydrate (127) and epitajixanthone hydrate (128), along with known compounds tajixanthone hydrate (129), 14-methoxyltajixanthone-25-acetate (130), and 15-chlorotajixanthone hydrate (131), questin (132) and carnemycin B (133, Figure 8), were purified from Emericella sp. XL029 residing inside the leaves of Panax notoginseng. Compounds 125–127, 130, 132, 133 exhibited potent activity against M. luteus, S. aureus, B. megaterium, B. anthracis, and B. paratyphosum B (MIC values ranging from 12.5 and 25 μg/mL). Compound 128 exhibited potent activity against M. luteus, S. aureus, B. megaterium, and B. paratyphosum B (MIC 25 μg/mL each), while compounds 129, 131 inhibited S. aureus, B. megaterium, and B. paratyphosum B (MIC 25 and 12.5 μg/mL). Compounds 125, 128, 133 displayed average activity against drug-resistant S. aureus (MICs 50 μg/mL each). All isolated compounds 125–133 displayed moderate activity against P. aeruginosa, E. coli, and E. aerogenes (MIC 50 μg/mL) [74].

An endophytic fungus Byssochlamys spectabilis from the plant Edgeworthia chrysantha yielded bysspectin C (134, Figure 8) which was active against E. coli and S. aureus with MIC values of 32 and 64 µg/mL, respectively [75].

Two new compounds, sydowianumols A (135), and B (136, Figure 8), were isolated from Poculum pseudosydowianum (TNS-F-57853), an endophytic fungus associated with the petiole of Quercus crispula var. crispula in Yoshiwa. Compounds 135 and 136 exhibited anti-MRSA activity, with MIC₉₀ values of 12.5 μg/mL [76].

Six previously undescribed halogenated dihydroisocoumarins, palmaerones A–C, (137–139) and E–G (140–142, Figure 8) were purified from Lachnum palmae, an endophytic fungus from Przewalskia tangutica by exposure to a histone deacetylase inhibitor SAHA. Compounds 137, 138, 140–142 were active against B. subtilis, with MIC values of 35, 30, 10, 50, and 55 μg/mL, respectively, while compounds 137–140, were found active against S. aureus with MIC values of 65, 55, 60, and 55 μg/mL, respectively [77].

The polyketide nemanifuranone A (143), a nordammarane triterpenoid, was isolated from Nemania serpens, an endophyte of Vitis vinifera. Additionally, a known metabolite 144, also a nordammarane triterpenoid (Figure 8) was isolated from the mycelium. Nemanifuranone A (143) showed modest activity against E. coli, with a MIC of 200 μg/mL, and significant inhibition (>75% inhibition) against S. aureus, B. subtilis and M. luteus at a concentration of 100–200 μg/mL. However, 144 showed significant inhibition (>75% inhibition) of M. luteus at a concentration of 100 μg/mL [78].

A sesquiterpene, variabilone (145, Figure 9), with a new skeleton, was isolated from the endophytic fungus Paraconiothyrium variabile isolated from Cephalotaxus harringtonia. Compound 145 behaved as a potent growth inhibitor of B. subtilis at an IC₅₀ of 2.13 μg/mL after 24 h [79].

A new 4-hydroxycinnamic acid derivative compound, methyl 2-{(E)-2-[4-(formyloxy)phenyl]ethenyl}-4-methyl-3-oxopentanoate (146), along with the known compounds (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethylperhydro-1,4-oxazine-2,5-dione (147), (3R,6R)-N-methyl-N-(1-hydroxy-2-methylpropyl)-phenylalanine (148), siccanol (149), sambutoxin (150, Figure 9) and fusaproliferin (106), were extracted from Pyronema sp. an endophyte of the Taxus mairei. Compounds 106, 146–150 also exhibited potential inhibitory activity, with IC₅₀s of 64, 59, 57, 84, 43 and 32 μM against Mycobacterium marinum, respectively [80].

Three new natural furanones, pulvinulin A (151), graminin C (152), and cis-gregatin B (153), together with the known fungal metabolite, graminin B (154, Figure 9), were isolated from Pulvinula sp. 11120, an endophyte of the leaves of Cupressus arizonica. Compounds 151–154 displayed antibacterial against E. coli with 12, 18, 16, and 14 mm zones of inhibition [81].

Stelliosphaerols A (155) and B (156, Figure 9), new sesquiterpene−polyol conjugates were purified from a Stelliosphaera formicum endophytic fungus associated with the plant Duroia hirsuta. Compounds 155 and 156 inhibited S. aureus with MIC values of 250 μg/mL [82].

Two novel polyketides, cis-4-acetoxyoxymellein (157) and 8-deoxy-6-hydroxy-cis-4-acetoxyoxymellein (158, Figure 9) were extracted from an unidentified ascomycete, associated with Melilotus dentatus. Compound 157 was found to be active against E. coli and B. megaterium with 10 and 10 (partial inhibition) zones of inhibition at 0.05 mg concentration. Compound 158 displayed antibacterial activity against E. coli and B. megaterium with 9 and 9 (partial inhibition) zones of inhibition at a concentration of 0.05 mg [83].

2.2. Anamorphic Ascomycetes

Anamorphic Ascomycetes are the fungi that are the asexual form of ascomycetes. The first antibiotic penicillin-producing fungi belonged to this group. Fungi belonging to this group are prolific producers of bioactives metabolites. After the discovery of penicillin, this group is extensively screened for bioactives. Some important genera in this group are Penicillium, Aspergillus, Fusarium, Pestalotiopsis, Phoma and Colletotrichum. Here we report the antibacterials compounds from this group of fungi.

2.2.1. Aspergillus

Aspergillus is one of the important fungal genera and some of the antibacterials from this genus such as aspochalasin P (159), alatinone (160), β-11-methoxycurvularine (161), and 12-keto-10,11-dehydrocurvularine (162, Figure 9) were purified from Aspergillus sp. FT1307 associated with plant Heliotropium sp. Compounds 159–162 showed weak activity against Staphylococcus aureus ATCC12600, Bacillus subtilis ATCC6633 and MRSA ATCC43300 with MICs in the range of 40 to 80 μg/mL [84].

A new polyketide, aspergillone A (163, Figure 10), was isolated from Aspergillus cristatus associated with Pinellia ternata. Aspergilline A (163) is the first example of a bicyclo[2.2.2] diazaoctane indole alkaloid where the diketopiperazine structure is constructed from tryptophan and alanine. Aspergillone A (163) exhibited average antibacterial activities against B. subtilis and S. aureus, with MIC₅₀ values of 8.5 and 32.2 μg/mL, respectively [85].

A new quinolone derivative, (22S)-aniduquinolone A (164) and its known isomer (22R)-aniduquinolone A (165, Figure 10) were purified from the endophytic fungus Aspergillus versicolor strain Eich.5.2.2 from the petals of flowers of Eichhornia crassipes. The epimers 164/165 together exhibited significant antibacterial activity against S. aureus, with a MIC of 0.4 μg/mL [86].

A new diaryl ether derivative aspergillether B (166, Figure 10) was separated from Aspergillus versicolor residing inside the roots of Pulicaria crispa. Compound 166 exhibited significant antibacterial capacity towards S. aureus, Bacillus cereus, and E. coli with MICs values of 4.3, 3.7, and 3.9 μg/mL, respectively [87].

The known compound 3-O-β-D-glucopyranosyl stigmasta-5(6),24(28)-diene (167, Figure 10) was extracted from an endophytic fungus Aspergillus ochraceus SX-C7 eus SX-C7 from Setaginella stauntoniana and displayed inhibitory activity against B. subtilis with a MIC value of 2 μg/mL [88].

A prenylated benzaldehyde derivative, dihydroauroglaucin (168, Figure 10), was isolated from Aspergillus amstelodami (MK215708) an endophytic fungi of Ammi majus, a plant indigenous to Egypt. Compound 168 showed activity against E. coli, Streptococcus mutans and S. aureus, with MICs of 1.95, 1.95 and 3.9 μg/mL, respectively. The highest antibiofilm activity at concentrataion 7.81 μg/mL against S. aureus and E. coli biofilms, at 15.63 μg/mL concentration against S. mutans and moderate activity (MBIC = 31.25 μg/mL) against P. aeruginosa biofilm was measured [89].

Two cysteine residue-containing merocytochalasans, cyschalasins A (169) and B (170, Figure 10) were isolated from Aspergillus micronesiensis associated with the root of Phyllanthus glaucus. Compounds 169 and 170 displayed anti-MRSA activity with MIC₅₀ values of 17.5 and 10.6 μg/mL and MIC₉₀ values of 28.4 and 14.7 μg/mL, respectively [90].

Methylsulochrin (171, Figure 10) is a diphenyl ether derivative isolated from A. niger associated with the stems of Acanthus montanus. It inhibits Enterobacter cloacae, Enterobacter aerogenes and S. aureus with MIC values of 7.8, 7.8 and 15.6 μg/mL, respectively [91].

A new furan derivative named 3-(5-oxo-2,5-dihydrofuran-3-yl) propanoic acid (172, Figure 10) was purified from Aspergillus tubingensis, an endophyte from the stems of Decaisnea insignis. Compound 172 inhibited Streptococcus lactis with MIC value of 32 μg/mL [92].

A new compound, methyl 2-(4-hydroxybenzyl)-1,7-dihydroxy-6-(3-methylbut-2-enyl)-1H-indene-1-carboxylate (173, Figure 10) was extracted from Aspergillus flavipes Y-62, associated with the plant Suaeda glauca. Compound 173 showed poor activity against MRSA, with an MIC value of 128 μg/mL, and against K. pneumoniae and P. aeruginosa with equal MIC values of 32 μg/mL [93].

The alkaloids 4-amino-1-(1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl)-1H-1,2,3-triazole-5(4H)one (174) and 3,6-dibenzyl-3,6-dimethylpiperazine-2,5-dione (175, Figure 10) were obtained from Aspergillus sp. isolate of Zingiber cassumunar rhizome. Compounds 174 and 175 exhibited inhibitory activity against X. oryzae and E. coli, with a 16–30 mm zone of inhibition [5].

Aspergillus fumigatus, an endophyte associated with Edgeworthia chrysantha, was the source of pseurotin A (176) and spirotryprostatin A (177, Figure 10). Compounds 176, 177 displayed good antibacterial activity against S. aureus (MIC 0.39 µg/mL each). Compound 177 also showed potent antibacterial activity against E. coli (MIC of 0.39 µg/mL) [94].

Six compounds, fumiquinazoline J (178, Figure 10), fumiquinazoline I (179), fumiquinazoline C (180), fumiquinazoline H (181), fumiquinazoline D (182), and fumiquinazoline B (183, Figure 11) were extracted from Aspergillus sp., residing inside the plant Astragalus membranaceus. Compounds 178, 180–182 displayed potent activity against B. subtilis, E. coli, P. aeruginosa and S. aureus (MICs in the range of 0.5–8 μg/mL). Compounds 179, 183 displayed moderate activity against B. subtilis, E. coli, P. aeruginosa and S. aureus with MICs of 4–16 μg/mL [95].

An antibacterial polyketide named (-) palitantin (184, Figure 11) was isolated from Aspergillus fumigatiaffnis, an endophyte of the medicinal plant Tribulus terrestris, which displayed antibacterial activity against E. faecalis UW 2689 and S. pneumoniae with MIC values of 64 μg/mL each [96].

A novel terpene-polyketide hybrid, i.e., a meroterpenoid, aspermerodione (185), and a new heptacyclic analog and iconin C (186, Figure 11) were purified from Aspergillus sp. TJ23 residing inside the plant Hypericum perforatum. Compound 185 showed antibacterial activity against MRSA (MIC of 32 μg/mL), whereas compound 186 showed poor anti- MRSA activity (>100 μg/mL). Aspemerodione (186) worked synergistically with the antibiotics oxacillin and piperacillin against MRSA and was found to be a potential inhibitor of PBP2a [97].

Aspergillus sp. YXf3, an endophyte residing inside the leaves of Ginkgo biloba, yielded some novel p-terphenyls named prenylterphenyllin D (187), prenylterphenyllin E (188), and 2′-O-methylprenylterphenyllin (189), along with the known compounds prenylterphenyllin (190) and prenylterphenyllin B (191, Figure 11). Compounds 187–191 displayed antibacterial activity against X. oryzae pv. oryzicola and E. amylovora with the same MIC values of 20 μg/mL, while compound 191 exhibited activity against E. amylovora with a MIC value of 10 μg/mL [98].

Nine new phenalenone derivatives, aspergillussanone D (192), aspergillussanone E (193), F (194) G (195) H (196), I (197), J (198), K (199), along with two known analogues, the aspergillussanones L (200 and 201, Figure 11) were extracted from Aspergillus sp. residing inside the plant Pinellia ternate. Compound 200 exhibited good antimicrobial activity against P. aeruginosa, S. aureus, and B. subtilis (MIC₅₀ values of 1.87, 2.77, and 4.80 μg/mL). Compound 192 exhibited the antibacterial activity against P. aeruginosa, and S. aureus, (MIC₅₀ of 38.47 and 29.91 μg/mL). Compound 193 was found to be selectively active against E. coli (MIC₅₀ of 7.83 μg/mL). Compound 194 exhibited antimicrobial activity against P. aeruginosa, and S. aureus, (MIC₅₀ values of 26.56, 3.93 and 16.48 μg/mL). Compound 195 inhibited P. aeruginosa, and S. aureus, (MIC₅₀ values of 24.46 and 34.66 μg/mL). Compound 196 inhibited P. aeruginosa, and E. coli, (MIC₅₀ values of 8.59 and 5.87 μg/mL). Compound 197 selectively inhibited P. aeruginosa, (MIC₅₀ of 12.0 μg/mL). Compound 198 exhibited activity against P. aeruginosa, E. coli and S. aureus with MIC₅₀ values of 28.50, 5.34 and 29.87 μg/mL, respectively. Compound 199 exhibited antibacterial activity against P. aeruginosa, and S. aureus, (MIC₅₀ values of 6.55 and 21.02 μg/mL). Compound 201 inhibited P. aeruginosa, and E. coli, with MIC₅₀ values of 19.07 and 1.88 μg/mL, respectively [99].

The compound terrein (202, Figure 12), a polyketide, was extracted from Aspergillus terreus JAS-2 associated with Achyranthus aspera. Terrein (202) exhibited antibacterial activity with an IC₅₀ value of 20 μg/mL against E. faecalis, and more than 20 μg/mL against Aeromonas hydrophila and S. aureus, as the compound showed only 48% and 38.3% inhibition [100].

A known compound (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (203, Figure 12), was purified from the Aspergillus terreus isolate of Carthamus lanatus. Compound 203 displayed potent anti-MRSA activity, with IC₅₀ values of 2.29 µM compared to ciprofloxacin (IC₅₀ 0.21 µM) [101].

A new furan derivative named 5-acetoxymethylfuran-3-carboxylic acid (204), along with the furan compound 5-hydroxymethylfuran-3-carboxylic acid (205, Figure 12), were obtained from Aspergillus flavus, isolated from Cephalotaxus fortunei. The compounds 204–205 inhibited S. aureus with MIC values of 15.6 and 31.3 μg/mL, respectively [102].

A new compound, allahabadolactone B (206), and the known compound ergosterol peroxide (207, Figure 12) were purified from Aspergillus allahabadii BCC45335 residing inside the roots of Cinnamomum subavenium. Compounds 206–207 displayed antimicrobial activity against B. cereus with IC₅₀ values of 12.50 and 3.13 µg/mL, respectively [103].

A new pyrone named 6-isovaleryl-4-methoxy-pyran-2-one (208), along with three known pyrone compounds, rubrofusarin B (209), asperpyrone A (210) and campyrone A (211, Figure 12), was purified from Aspergillus tubingensis isolated from the roots of Lycium ruthenicum. Compound 209 possessed potent activity against E. coli with a MIC of 1.95 μg/mL while the compounds 208, 210, 211 showed poor activity against E. coli, P. aeruginosa, S. aureus and Streptococcus lactis [104].

A new cyclic pentapeptide, malformin E (212, Figure 12), was extracted from Aspergillus tamarii FR02 associated with Ficus carica. Compound 212 displayed potent activity against B. subtilis, S. aureus, P. aeruginosa, and E. coli with MIC values of 0.91, 0.45, 1.82, and 0.91 μM, respectively [105].

A new butyrolactone, aspernolide F (213), together with a known stigmasterol derivative, (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (203, Figure 12), were purified from Aspergillus terreus, an endophyte of Carthamus lanatus. Compound 203 displayed a potent anti-MRSA activity, with an IC₅₀ value of 0.96μg/mL while compound 213 displayed poor anti-MRSA activity (IC₅₀ 6.39μg/mL) [106].

The metabolites 1-(3,8-dihydroxy-4,6,6-trimethyl-6H-benzochromen-2-yloxy)propane-2-one (214), 5-hydroxy-4-(hydroxymethyl)-2H-pyran-2-one (215) and 5-hydroxy-2-oxo-2H-pyran-4-yl)methyl acetate (216, Figure 12) were purified from Aspergillus sp. (SbD5) associated with the plant Andrographis paniculata. Compounds 214–216 displayed poor to average activity against S. aureus, E. coli, S. dysenteriae and Salmonella typhi with an inhibition zone diameter ranging from 8.1 to 12.1 mm at a concentration 500 μg/mL [107].

The compounds xanthoascin (217), prenylterphenyllin B (218) and prenylcandidusin (219, Figure 12), were extracted from Aspergillus sp. IFB-YXS, associated with the leaves of Ginkgo biloba. Compound 217 displayed antibacterial activity against X. oryzae pv. oryzicola, E. amylovora, P. syringae pv. lachrymans and C. michiganense subsp. sepedonicus with MICs of 20, 10, 5.0 and 0.31 µg/mL, respectively. Compound 218 exhibited antibiotic activities with MICs of 20 µg/mL each towards X. oryzae pv. oryzicola, E. amylovora, P. syringae pv. lachrymans, respectively. Compound 219 was found to be effective against X. oryzae pv. oryzae and X. oryzae pv. oryzicola (MIC of 10 and 20 µg/mL). It was observed that compound 217 can change the permeability and cause nucleic acid leakage of the cytomembrane of the phytopathogen [108].

2.2.2. Penicillium

New β-resorcylic acid lactones, including 4-O-desmethyl-aigialomycin B (220, Figure 12), and penochrochlactones C (221), and D (222, Figure 13), were purified from Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia. Compounds 220–222 exhibited moderate activities against S. aureus, B. subtilis, E. coli, and P. aeruginosa with MIC values between 9.7 and 32.0 μg/mL [109].

The compound p-hydroxybenzaldehyde (223, Figure 13), was isolated from Penicillium brefeldianum, an endophyte residing inside the root bark of Syzygium zeylanicum. Compound 223 was found to be active against S. typhi, E. coli, and B. subtilis with MIC values of 64 g/mL. p-Hydroxybenzaldehyde was also reported from Syzygium zeylanicum [110].

An endophytic fungus, Penicillium vulpinum GDGJ-91, from the roots of Sophorae tonkinensis, yielded the new compound 10-demethylated andrastone A (224), and four known analogs, 15-deacetylcitreohybridone E (225), citreohybridonol (226) and andrastins A (227) and B (228, Figure 13). Compounds 224 and 227 displayed good activity against Bacillus megaterium (MIC value of 6.25 μg/mL), and compounds 225, 226, 228 showed average activity against Bacillus megaterium (MIC of 25, 12.5 and 25 μg/mL). Compound 226 showed potent antibacterial activity against B. paratyphosus B at 6.25 μg/mL, while the other compounds showed average activities against B. paratyphosus B at 12.5 or 25 μg/mL and compound 226 also exhibited moderate activities against E. coli and S. aureus with MIC values of 25 μg/mL [111].

A novel N-methoxy-1-pyridone alkaloid, chromenopyridin A (229), and the already reported compound viridicatol (230, Figure 13) were purified from Penicillium nothofagi P-6, residing inside the bark of Abies beshanzuensis. Compounds 229 and 230 exhibited antibacterial activity against S. aureus, with MIC values of 62.5 and 15.6 μg/mL, respectively [112].

ω-Hydroxyemodin (231, Figure 13) a polyhydroxy anthraquinone, was extracted from Penicillium restrictum (strain G85) from Silybum marianum. Compound 231 showed inhibition against MRSA as a quorum sensing inhibitor in both in vitro and in vivo systems [113].

Two new phthalide derivatives, (−)-3-carboxypropyl-7-hydroxyphthalide (232) and (−)-3-carboxypropyl-7-hydroxyphthalide methyl ester (233, Figure 13), were isolated from Penicillium vulpinum residing inside the plant S. tonkinensis. Compound 232 exhibited a medium inhibition against Shigella dysenteriae, Enterobacter areogenes, B. subtilis, B. megaterium, and Micrococcus lysodeikticus with MIC value between 12.5–50 μg/mL. Compound 233 showed average activity against E. areogenes with MIC value of 12.5 μg/mL, and showed poor activity against B. subtilis, B. megaterium and M. lysodeikticus with MIC values of 100 μg/mL [114].

Citridone E (234), a new phenylpyridone derivative, and the previously reported compound (–)-dehydrocurvularin (235, Figure 13) were purified from Penicillium sumatrense GZWMJZ-313 associated with the plant Garcinia multiflora. Compounds 234 and 235 showed antibacterial activity against S. aureus, P. aeruginosa, Clostridium perfringens, and E. coli (with MICs ranging from 32 to 64 μg/mL) [115].

Three new 3,4,6-trisubstituted α-pyrone derivatives, namely 6-(2′R-hydroxy-3′E,5′E-diene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (236), 6-(2′S-hydroxy-5′E-ene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran2-one (237), and 6-(2′S-hydroxy-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (238), along with the previously reported compound trichodermic acid (239, Figure 13), were purified from Penicillium ochrochloron associated with Taxus media. Compounds 236–239 displayed antimicrobial activity with MIC values ranging from 25 to 50 μg/mL against B. subtilis, B. megaterium, E. coli, Enterobacter aerogenes, Micrococcus luteus, Proteusbacillm vulgaris, P. aeruginosa, S. aureus, Salmonella enterica, and Salmonella typhi [116].

Three new compounds, brasiliamide J-a (240), brasiliamide J-b (241) and peniciolidone (242, Figure 13), as well as the known compound austin (243, Figure 14), were isolated from Penicillium janthinellum SYPF 7899 associated with the plant Panax notoginseng. Compound 240 exhibited potent activity against B. subtilis and S. aureus (MICs of 15 and 18 μg/mL). Compounds 241 and 243 showed average inhibitory activities against B. subtilis (MIC 35 μg/mL and 50 μg/mL, respectively) and S. aureus (MIC 39 μg/mL and 60 μg/mL, respectively). In addition, compound 240 also affected the length of B. subtillius. Similarly, coccoid cells of S. aureus also swelled 2-fold after treatment with compound 240. Compounds 240, 241, 242 showed high binding energies, strong H-bond interactions and hydrophobic interactions with filamentous temperature-sensitive protein Z (FtsZ) [117].

The new compounds penicimenolidyu A (244), and penicimenolidyu B (245) and the known compound rasfonin (246, Figure 14) were purified from Penicillium cataractarum SYPF 7131 obtained from the plant Ginkgo biloba. Compound 246 exhibited good antibacterial activity against S. aureus, with a MIC value of 10 μg/mL. Compounds 245 and 246 showed moderate inhibitory activity against S. aureus (MIC 65 μg/mL and 59 μg/mL). The docking results revealed that compounds 244–246 possess high binding energies, strong H-bond interactions and hydrophobic interactions with FtsZ from S. aureus, validating the observed antimicrobial activity [118].

A rare dichloroaromatic polyketide, 3′-methoxycitreovirone (247) along with known metabolites cis-bis-(methylthio)-silvatin (248), citreovirone (249), trypacidin A (250, Figure 14) and helvolic acid (100), were obtained from endophytic Penicillium sp. of Pinellia ternate. Compound 100 displayed potent antibacterial activity against S. aureus and P. aeruginosa (MIC = 5.8 and 4.6 μg/mL) as well as mild activity against B. subtilis and E. coli (MIC = 42.2 and 75.0 μg/mL). Compounds 247 and 249 were found to have moderate antibacterial activity against E. coli and S. aureus (MIC = 62.6 and 76.6 μg/mL). Compounds 248 and 250 exhibited poor antibacterial activity against S. aureus with MIC values of 43.4 and 76.0 μg/mL and 250 also displayed effect against B. subtilis (MIC = 54.1 μg/mL) [119].

A known quinolinone alkaloids viridicatol (251, Figure 14) was obtained from Penicillium sp. R22 was associated with Nerium indicum and displayed potent antibacterial activity against S. aureus with MIC value of 15.6 μg/mL [120]. The novel compound penicitroamide (252, Figure 14), was purified from Penicillium sp. (NO. 24) isolated from the leaves of Tapiscia sinensis. Compound 252 displayed potent antibacterial activity against plant pathogens, Erwinia carotovora sub sp. carotovora (Jones) Bersey, et al. with MIC₅₀ at 45 μg/mL [121].

Penialidins A-C (253–255), citromycetin (256), p-hydroxyphenylglyoxalaldoxime (257) and brefelfin A (258, Figure 14) were purified from the Penicillium sp. CAM64 a fungus associated with the plant Garcinia nobilis. Compounds 253–258, exhibited antibacterial activity against Vibrio cholerae SG24 (1), V. cholerae CO6, V. cholerae NB2, V. cholerae PC2, S. flexneri SDINT (MIC = 0.50–128 μg/mL). Compound 255 exhibited potent activity against V. cholerae SG24 (1), V. cholerae CO6, V. cholerae NB2, V. cholerae PC2, S. flexneri SDINT, with MIC values of 0.50, 16, 8, 0.50 and 8 μg/mL, respectively following in decreasing order of activity by compound 254 (MIC = 4–32 μg/mL), compound 257 (MIC = 8–32 μg/mL), compound 257 (MIC = 32–64 μg/mL) and compounds 256 and 258 (MIC = 64–128 μg/mL) [122].

Purpureone (259, Figure 14) was extracted from Purpureocillium lilacinum, residing inside the roots of Rauvolfia macrophylla. Compound 259 displayed antibacterial activity with the zone of inhibition of 10.6, 12.3, 13.0, 8.7, 12.3, and 10.0 mm against B. cereus, L. monocytogenes, E. coli, K. pneumoniae, P. stuartii, and P. aeruginosa (6 mm filter paper disks impregnated with 10 μL of compound) [123].

2.2.3. Fusarium

Secondary metabolites identified as 2-methoxy-6-methyl-7-acetonyl-8-hydroxy-1,4-maphthalenedione (260) 5,8-dihydroxy-7-acetonyl-1,4-naphthalenedione (261, Figure 14), anhydrojavanicin (262), and fusarnaphthoquinone B (263, Figure 15), were purified from Neocosmospora sp. MFLUCC 17-0253 associated with Rhizophora apiculata. All three compounds showed potent antibacterial against Acidovorax citrulli (responsible for bacterial fruit blotch (BFB) a bacterial disease of Cucurbitaceae crops) with MIC values of 0.0075 mg/mL (mixture of 260, 261), 0.004 mg/mL (262), 0.025 mg/mL (263). Compounds 260–263 significantly inhibited biofilm development of Acidovorax citrulli, thus demonstrating that these metabolites can be used for biological control of bacterial fruit blotch of watermelon and melon [124].

A new aminobenzamide derivative, namely fusaribenzamide A (264, Figure 15), was purified from Fusarium sp. of Mentha longifolia. Compound 264 displayed antibacterial activity against S. aureus and E. coli with MIC values of 62.8 and 56.4 μg/disc, respectively [125].

Two alkaloids, indol-3-acetic acid (265), bassiatin (266), a depsipeptide, beauvericin (267), two sesquiterpenoids, cyclonerodiol (268), epicyclonerodiol oxide (269), four 1,4-naphthoquinones, 5-O-methylsolaniol (270), 5-O-methyljavanicin (271), fusarubin methyl ether (272), and anhydrojavanicin (273, Figure 15) and a sesterterpene, fusaproliferin (106), were separated from the green Chinese onion-derived fungus F. proliferatum AF-04. Compounds 270–273 displayed good antibacterial activity against B. megaterium with MICs of 25 μg/mL each; compounds 265, 267, 269 displayed moderate activity with MICs of 50 μg/mL each and compound 268, displayed activity with an MIC of 12.50 μg/mL. Compounds 266, 270–272 displayed good antibacterial activity against B. subtilis, with MICs of 50 μg/mL each. Compounds 269 and 272 were found to be active against E. coli with MIC values of 50 μg/mL each and compounds 270, 271, 273 with MIC values of 25 μg/mL, respectively. Compounds 269–272 displayed antibacterial activity against Clostridium perfringens with MIC values of 50, 50, 12.5 and 50 μg/mL, respectively. Compounds 267, 106, 270–273 displayed anti-MRSA activity with MIC values of 50, 50, 12.5, 12.5, 12.5, and 25μg/mL, respectively. Compounds 270–273 displayed antibacterial activity against RN4220 (MICs of 50 μg/mL each). Compounds 272, 273 showed inhibition against NewmanWT (MICs of 50 μg/mL each). Compound 266 displayed antibacterial activity against NewmanWT with a MIC value of 50 μg/mL each. [126].

Fusarium sp. TP-G1 an endophyte of Dendrobium officinable, was the source of the compounds trichosetin (274), beauvericin A (275), enniatin B (276), enniatin H (277), enniatin I (278), enniatin MK1688 (279), fusaric acid (280) and dehydrofusaric acid (281, Figure 15) and beauvericin (267). Compounds 267, 274, 275, 277–279 displayed antibacterial activity against S. aureus and MRSA with IC₅₀ values in the range of 2–32 μg/mL. Compounds 280, 281 displayed antimicrobial activity against Acinetobacter baumannii with a MIC value of 64 μg/mL and 128 μg/mL, respectively. Compound 276 inhibited S. aureus and MRSA with IC₅₀ value of 128 μg/mL each [127].

A new spiromeroterpenoid, namely fusariumin A (282), together with the previously reported terpenoids asperterpenoid A (283) and agathic acid (284, Figure 15), were purified from Fusarium sp. YD-2 associated with the plant Santalum album. Compound 282 showed antibacterial activity against pathogenic S. aureus and P. aeruginosa (MIC of 6.3 μg/mL), and compound 283 showed average activity against pathogenic Salmonella enteritidis and Micrococcus luteus (MICs of 25.2 and 6.3 μg/mL). Compound 284 showed moderate activities against B. cereus and M. luteus, with MIC values of and 12.5 and 25.4 μg/mL, respectively [128].

A new aminobenzamide derivative, namly fusarithioamide B (285, Figure 16), was separated from Fusarium chlamydosporium an endophyte of Anvillea garcinii and exhibited antibacterial activity against E. coli, B. cereus, and S. aureus (MIC values of 3.7, 2.5 and 3.1 µg/mL) [129].

The compounds 3,6,9-trihydroxy-7-methoxy4,4-dimethyl-3,4-dihydro-1H-benzo[g] isochromene-5,10-dione (286), fusarubin (287), 3-O-methylfusarubin (288) and javanicin (289, Figure 16) were extracted from Fusarium solani A2 residing inside the plant Glycyrrhiza glabra. Compounds 286–289 showed inhibition of B. subtilis, B. cereus, E. coli, S. aureus, K. pneumonia, S. pyogenes, and Micrococcus luteus (MICs in the range of < 1 to 256 μg/mL). Fusarubin (287) showed good activity against M. tuberculosis strain H37Rv with a MIC value of 8 μg/mL, whereas compounds 286, 288, 289 exhibited moderate activity with MIC values of 256, 64, 32 μg/mL, respectively [130].

A new benzamide derivative, fusarithioamide A (290, Figure 16) was characterized from Fusarium chlamydosporium, an endophyte of Anvillea garcinii. Compound 290 had antibacterial potential towards B. cereus, S. aureus, and E. coli with MIC values of 3.1, 4.4, and 6.9 μg/mL, respectively [131].

The polyketide javanicin (289, Figure 16) was purified from Fusarium sp. associated with Rhoeo spathacea, and displayed activity against M. tuberculosis with a MIC value of 25 μg/mL and M. phlei with a MIC value of 50 μg/mL [132].

Helvolic acid methyl ester (291, Figure 16), a new helvolic acid derivative, together with previously reported hydrohelvolic acid (292, Figure 16), and helvolic acid (100) were isolated from a Fusarium sp. residing inside the plant Ficus carica. Compound 291 was found to be active against B. subtilis, S. aureus, E. coli and P. aeruginosa (MIC between 3.13 to 12.5, μg/mL). Compound 100 displayed activity against B. subtilis, S. aureus, E. coli and P. aeruginosa (MICs between 3.13 to 6.25 μg/mL). Compound 292 displayed activity against B. subtilis, S. aureus, E. coli and P. aeruginosa with MIC values between 3.13 to 12.5 μg/mL [133].

The compounds colletorin B (293) and 4,5-dihydroascochlorin (294, Figure 16) were purified from an endophytic Fusarium sp. fungus. Compounds 293 and 294 exhibited potent antibacterial activity towards B. megaterium, with 5 and 10 mm zones of inhibition at a concentration of 10 μg/mL [134].

The tetramic acid derivative equisetin (295, Figure 16) was isolated from a Fusarium sp. associated with Opuntia dillenii, and displayed antibacterial activity against B. subtilis with a MIC value of 8 and MICs of 16 μg/mL against S. aureus and MRSA [135].

2.2.4. Trichoderma

Pretrichodermamide A (296, Figure 16), a known compound, was isolated from Trichoderma harzianum, an endophyte of Zingiber officinale and displayed antimycobacterial activity towards M. tuberculosis with a MIC value of 25 μg/mL (50 μM) [136].

A new compound named koninginin W (297) and four known polyketides, namely koninginin D (298), 7-O-methylkoninginin D (299, Figure 16), koninginin T (300) and koninginin A (301, Figure 17) were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH30002 of Panax notoginseng. Compounds 297, 298, 301, showed the weak activity against B. subtilis with MICs of 128 μg/mL. Compounds 297 and 299, showed weak activity against S. typhimurium, with MIC values of 64 and 128 μg/mL; Compounds 297 and 300, showed the weak activity against E. coli with MICs of 128 μg/mL. [137].

Five new carotane sesquiterpenes, trichocarotins I–M (302–306), which have diverse substitution patterns, and seven known related analogues including CAF-603 (307), 7β-hydroxy CAF-603 (308), trichocarotins E–H (309–312), and trichocarane A (313, Figure 17) were purified from Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of Artemisia argyi. Compounds 302–313 displayed antibacterial activity against E. coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7β-hydroxy CAF-603 (308) displayed potent activity against Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL) [138].

Three new polyketides, trichodermaketone E (314), 4-epi-7-O-methylkoninginin D (315), and trichopyranone A (316), two new terpenoids, 3-hydroxyharziandione (317) and 10,11-dihydro-11-hydroxycyclonerodiol (318), together with three related known congeners, cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), and harziandione (321, Figure 17) were isolated from the endophytic fungus Trichoderma koningiopsis QA-3 associated with the plant Artemisia argyi. Compounds 314, 316–318, 321 displayed potent activities against E. coli, with MIC values ranging from 0.5 to 64 μg/mL, while compounds 316–321 showed inhibitory activities against M. luteus with MIC values ranging from 1 to 16 μg/mL, compounds 314, 315, 317–321, showed inhibitory activities against P. aeruginosa with MIC values ranging from 4 to 16 μg/mL, and compounds 314, 318–321 showed activities against V. parahaemolyticus with MIC values ranging from 4 to 16 μg/mL. Among the compounds tested, compound 317 showed the strongest activity against E. coli, with a MIC value of 0.5 µg/mL and compound 320 showed the strongest activity against M. luteus, with a MIC value of 1 µg/mL, comparable to that of the positive control chloramphenicol [139].

New highly oxygenated polyketides, 15-hydroxy-1,4,5,6-tetra-epi-koninginin G (322), koninginin U (323, Figure 17) and 14-ketokoninginin B (324, Figure 18), were isolated from Trichoderma koningiopsis QA-3, isolated from Artemisia argyi. Compound 322 displayed good activity against the aquatic pathogen Vibrio alginolyticus, with a MIC value of 1 μg/mL. Compounds 323, 324 exhibited activity against aquatic bacteria Vibrio harveyi and Edwardsiella tarda with MICs of 4 and 2 µg/mL, respectively [140].

A new harziane diterpenoid with a 4/7/5/6 tetracyclic scaffold, harzianol I (325, Figure 18) was isolated from Trichoderma atroviride B7, an endophyte associated with the plant Colquhounia coccinea var. mollis. Compound 325 exhibited potent inhibitory activity against S. aureus, B. subtilis, and M. luteus, with EC₅₀ values of 7.7, 7.7, and 9.9 μg/mL, respectively [141].

The compound dendrobine (326, Figure 18) was purified from Trichoderma longibrachiatum MD33, an endophyte of Dendrobium nobile. Compound 326 inhibited Bacillus mycoides, B. subtilis, and Staphylococcus spp., with zones of inhibition of 9, 12 and 8 mm, respectively [142].

Trichocadinins B-D and G (327–330, Figure 18), new cadinane-type sesquiterpene derivatives, were isolated from Trichoderma virens QA-8 residing inside the plant Artemisia argyi. Compounds 327–330 displayed antibacterial activity against E. coli, Aeromonas hydrophilia QDIO-1, Edwardsiella tarda, E. ictarda, Micrococcus luteus, P. aeruginosa, Vibrio alginolyticus, V. anguillarum, V. harveyi, V. parahemolyticus, and V. vulnificus (MICs in the range of 8–64 μg/mL). Compound 330 inhibited Ed. tarda and V. anguillarum with MIC values of 1 and 2 μg/mL, respectively [143].

New diterpenes koninginols A (331) and B (332, Figure 18) were isolated from Trichoderma koningiopsis A729, an endophyte of Morinda officinalis. Compounds 331–332 exhibited potent inhibition against B. subtilis, with MIC values of 10 and 2 μg/mL, respectively [144].

Trichoderma koningiopsis QA-3, isolated from the plant Artemisia argyi, produced five new polyketides: ent-koninginin A (333), 1,6-di-epi-koninginin A (334), 15-hydroxykoninginin A (335), 10-deacetylkoningiopisin D (336) and koninginin T (337) and two known analogs, koninginin L (338), trichoketide A (339, Figure 18). Compounds 333 and 339 inhibited the aquatic bacteria E. tarda, V. anguillarum, and V. parahemolyticus, and the human pathogen E. coli (MICs ranging from 8 to 64 μg/mL). Compound 333 also showed activity against the aquatic bacteria M. luteus and P. aeruginosa and agropathogens. Compounds 333–339 were found to be active against E. coli (each with MIC values of 64 μg/mL) and E. tarda, V. alginolyticus, and V. anguillarum (MICs ranging from 8 to 64 μg/mL) while compounds 333 and 339 also showed antimicrobial activity against M luteus, V. parahemolyticus, and V. vulnificus (MIC values ranging from 4 to 64 μg/mL). Compound 333 was also found active against V. vulnificus with a MIC of 4 μg/mL [145].

2.2.5. Alternaria

A novel polyketide derivative, isotalaroflavone (340), along with the known compounds 4-hydroxyalternariol-9-methyl ether (341) and verrulactone A (342, Figure 18) were obtained from Alternaria alternata ZHJG5 that was isolated from the leaves of Cercis chinensis collected from Nanjing Botanical Garden (Nanjing, China). Compounds 340–342 were found to be active against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc) and Ralstonia solanacearum (Rs) with MICs ranging from 0.5 to 64 μg/mL. In addition, compound 340 showed a potent protective effect against rice bacterial leaf blight caused by Xoo with a protective efficacy of 75.1% at a concentration of 200 μg/mL [146].

A new biphenyl compound altertoxin VII (343), and the related compounds altenuisol (344, Figure 19), alternariol (44), were purified from Alternaria sp. PfuH1 is associated with Pogostemon cablin. Compounds 44, 343, 344 showed activity against S. agalactiae with MIC values of 9.3, 17.3, and 85.3, μg/mL, respectively, and compound 343 also showed poor activity against E. coli with MIC value of 128 μg/mL [147].

Known metabolites altenuisol (344), alterlactone (345), and dehydroaltenusin (346, Figure 19) and alternariol (44), were isolated from Alternaria alternata ZHJG5 residing inside the leaves of Cercis chinensis. The compounds 44, 344, 345, 346, showed inhibitory activities on FabH of X. oryzae pv. oryzae (Xoo) with IC₅₀ values ranging from 29.5 to 74.1 μM and also displayed a varying degree of antibacterial activities against X. oryzae pv. oryzae (Xoo) with MIC values ranging from 4 to 64 μg/mL. Molecular modeling was then used to picture how these compounds interact with XooFabH. Compounds 44, and 343, displayed significant bactericidal activity against rice bacterial leaf blight with a protective efficiency of 66.2 and 82.5% at concentration of 200 μg/mL, respectively [148].

The compound alternariol 9-Me ether (347, Figure 19) was purified from Alternaria alternata MGTMMP031 associated with Vitex negundo. Compound 347 exhibited potential activity against B. cereus, Klebsiella pneumoniae with a MIC at 30 µM/L. The compound inhibited the growth of E. coli, Salmonella typhi, Proteus mirabilis, S. aureus and S. epidermidis at a MIC of 35 µM/L [149].

An endophytic fungus, Alternaria alternata, associated with Grewia asiatica yielded a new structural isomer of alternariol, i.e., 3,7-dihydroxy-9-methoxy-2-methyl-6H-benzo[c]-chromen-6-one (348, Figure 19), along with alternariol (44). Compound 44 inhibited S. aureus, VRE, and MRSA with MIC values of 32, 32 and 8 μg/mL, respectively. Compound 348 also inhibited S. aureus, VRE, and MRSA with MIC values of 128, 128, and 64 μg/mL, respectively [150].

The compounds 4-hydroxyalternariol-9-methyl ether (349, Figure 19) altenuisol (344), and alternariol (44) were purified from Alternaria sp. Samif01, an endophytic fungus of Salvia miltiorrhiza. Compounds 44, 344, and 349 showed inhibition against A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, Staphylococcus hemolyticus and Xanthomonas vesicatorya with MIC values in the range of 86.7–364.7 μM [151]. Previously alternariol 9-Me ether (347, Figure 19) was isolated the same fungus and was found active against B. subtilis, S. haemolyticus, A. tumefaciens, P. lachrymans, R. solanacearum, and X. vesicatoria with IC₅₀ values ranging from 16.00 to 38.27 g/mL [152].

An endophytic fungus Alternaria sp. and Pyrenochaeta sp., purified from Hydrastis canadensis yielded altersetin (350) and macrosphelide A (351, Figure 19). Compounds 350 and 351 displayed antibacterial activity against S. aureus with MIC values of 0.23 and 75 μg/mL, respectively [153].

2.2.6. Simplicillium

The fungal strain Simplicillium lanosoniveum associated with Hevea brasiliensis, yielded a new depsidone, simplicildone K (352), together with the known compounds botryorhodine C (353), and simplicildone A (354, Figure 19). Compounds 353 and 354 displayed activity against S. aureus, MRSA with equal MIC values of 32 μg/mL, whereas 352 exhibited 4-fold less activity against both strains (MIC values of 128 μg/mL) [154].

The compounds botryorhodine C (353), and simplicildone A (354, Figure 19), were purified from Simplicillium sp. PSU-H41 which is associated with the leaves of Hevea brasiliensis. Compounds 353 and 354 exhibited poor activity against S. aureus (MIC of 32 μg/mL each). Compound 353 was found to be active against MRSA with the same MIC value [155].

2.2.7. Cladosporium

An endophytic fungus, Cladosporium cladosporioides, residing inside the leaves of Zygophyllum mandavillei yielded isocladosporin (355), 5′-hydroxyasperentin (356, Figure 19), 1-acetyl-17-methoxyaspidospermidin-20-ol (357), and 3-phenylpropionic acid (358, Figure 20). Compounds 355–358 displayed antibacterial activity against X. oryzae and Pseudomonas syringae with MIC values in the range of 7.81 to 125 µg/mL [156].

A new hybrid polyketide, named cladosin L (359, Figure 20) was discovered in the endophytic fungus Cladosporium sphaerospermum WBS017 associated with the bulbs of Fritillaria unibracteata var. wabuensis. Compound 359 inhibited S. aureus ATCC 29213 and S. aureus ATCC 700699 with MICs of 50 and 25 mM, respectively [157].

A naphthoquinone Me ether of fusarubin (360, Figure 20), was purified from a Cladosporium sp. associated with the Rauwolfia serpentina. Compound 360 (40 μg/disk) displayed potent activity against S. aureus, E. coli, P. aeruginosa and B. megaterium with 27, 25, 24 and 22 mm zones of inhibition, respectively and the activities were compared with kanamycin (30 μg/disk) [158].

2.2.8. Pestalotiopsis

The genus Pestalotiopsis is reported as an endophyte from rain forests in almost all parts of the world and is a prolific producer of chemically diverse bioactive compounds. One such compound is the new drimane sesquiterpenoid 11-dehydro-3a-hydroxyisodrimeninol (361, Figure 20), produced by Pestalotiopsis sp. M-23, an endophytic fungus of Leucosceptrum canum. Compound 361 displayed poor inhibitory effect against B. subtilis with IC₅₀ value of 280.27 μM [159].

The compounds (1S,3R)-austrocortirubin (362), (1S,3S)-austrocortirubin (363), and 1-deoxyaustrocortirubin (364, Figure 20), were obtained from Pestalotiopsis sp., an endophyte of Melaleuca quinquenervia. Compounds 362–364 displayed with poor antibacterial activity (100 μM) against Gram-positive isolates [160].

A new tetramic acid analog, neopestalotin B (365, Figure 20), was extracted from Neopestalotiopsis sp. and inhibited B. subtilis, S. aureus, S. pneumoniae, with MIC values of 10, 20, and 20 μg/mL, respectively [161].

2.2.9. Phoma

Two known thiodiketopiperazine derivatives 366 and 367 (Figure 20) were purified from Phoma cucurbitacearum (now known as Stagonosporopsis cucurbitacearum), an endophyte of Glycyrrhiza glabra. Compounds 366 and 367 were found to inhibit the battery of bacterial pathogens, including S. aureus and Streptococcus pyogenes with IC₅₀ values of <10 μM. Both compounds potentially inhibited biofilm formation in S. aureus and S. pyogenes and acted synergistically with streptomycin and inhibited transcription/translation. It was also observed that the sea gene was overexpressed by several fold on treatment with compound 366 while its expression was not affected significantly with compound 367. The expression of agrA gene was also not affected significantly in S. aureus with the treatment of either of the compounds [162].

Barceloneic acid C (368, Figure 20), purified from a Phoma sp. JS752 residing inside Phragmites communis. Compound (368) exhibited average antibacterial activities against Listeria monocytogenes and Staphylococcus pseudintermedius, (MIC of 1.02 μg/mL each) [163].

The polyketides thielavins T (369), U (370), and V (371, Figure 20) were purified from Setophoma sp., an endophytic fungus of Psidium guajava. Compounds 369–371 displayed antibacterial activity against pathogenic S. aureus with MIC values of 6.25, 50, and 25 μg/mL, respectively [164].

2.2.10. Colletotrichum

Two new γ-butyrolactone derives., colletolides A and B (372, 373), together with the already reported compounds sclerone (374, Figure 20), and 3-methyleneisoindolinon (375, Figure 21) were purified from Colletotrichum gloeosporioides B12, an endophyte of plant Illigera rhodantha. Compounds 372, 373, 375 were found to be active against Xanthomonas oryzae pv. oryzae, with the same MIC values of 128 μg/mL, while compound 374 was found active against X. oryzae pv. oryzae with MIC values of 64 μg/mL [165].

The new compounds colletotrichones A (376), B (377), and C (378, Figure 21) were purified from Colletotrichum sp. BS4 residing inside the leaves of Buxus sinica. Compound 376 inhibits E. coli and B. subtilis with MIC values 1.0 and 0.1 μg/mL, respectively. Compound 377 inhibited S. aureus with a MIC value of 5.0 μg/mL. Compound 378 has shown antibacterial activity against E. coli with a MIC value of 5.0 μg/mL [166].

2.2.11. Minor Taxa of Anamorphic Ascomycetes

New dibenzo-α-pyrones, rhizopycnolide A (379), rhizopcnin C (380) and rhizopycnin D (381), together with known congeners TMC-264 (382), palmariol B (383) penicilliumolide D (384, Figure 21) alternariol 9-methyl ether (347) and alternariol (44) and were purified from Rhizopycnis vagum (now known as Acrocalymma vagum) isolated from Nicotiana tabacum. Compounds 380, 384, 44 inhibited A. tumefaciens, B. subtilis, Pseudomonas lachrymans, R. solanacearum, Staphylococcus hemolyticus, and Xanthomonas vesicatoria, with MICs in the 25−100 μg/mL range. Rhizopycnolide A (379) was active against A. tumefaciens, B. subtilis, and P. lachrymans, with MIC values of 100, 75, and 100 μg/mL, respectively. Rhizopycnin D (381) was found to be active against A. tumefaciens, B. subtilis, and R. solanacearum, with an equal MIC value of 50 μg/mL, and against X. vesicatoria, with a MIC value of 75 μg/mL. TMC-264 (382) was selectively active against B. subtilis (MIC value of 50 μg/mL). Compounds 383 and 347 inhibited A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, and X. vesicatoria, with IC₅₀ values in the range 16.7−34.3 μg/mL [167].

Rhizoperemophilane K (385), 1α-hydroxyhydroisofukinon (386) and 2-oxo-3-hydroxy-eremophila-1(10),3,7(11),8-tetraen-8,12-olide (387, Figure 21) were purified from Rhizopycnis vagum (now known as Acrocalymma vagum), an endophyte of Nicotiana tabacum. Compounds 385, 386 and 387 displayed inhibition against A. tumefaciens, B. subtilis, P. lachrymans, Ralstonia solanacearum, S. haemolyticus, and X. vesicatoria, with MIC values in the range of 32~128 μg/mL [168].

Rhizopycnis acids A (388) and B (389, Figure 21), were purified from Rhizopycnis vagum (now known as Acrocalymma vagum) an endophyte of Nicotiana tabacum from China Agricultural University (Beijing, China). Compound 388 inhibited A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. hemolyticus and X. vesicatoria with MIC values of 20.82, 16.11, 23.48, 29.46, 21.11, and 24.31 µg/mL, respectively. Compound 389 also inhibited A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. haemolyticus, and X. vesicatoria with MIC values of 70.89, 81.28, 21.23, 43.40, 67.61, and 34.86 µg/mL, respectively [169].

Leptosphaeria sp. XL026 associated with Panax notoginseng yielded a new sesquiterpenoids, leptosphin B (390), along with three known diterpenes, conidiogenone C (391), conidiogenone D (392) and conidiogenone G (393, Figure 21). The site of the collection was Shijiazhuang (Hebei Province, China). Compounds 390–393 showed average antibacterial activity against B. cereus, with MIC values of 12.5–6.25 μg/mL and compound 392 also showed antibacterial activity against P. aeruginosa with a MIC value of 12.5 μg/mL [170].

Two 2-azaanthraquinones, scorpinone (394, Figure 21) and 5-deoxybostrycoidin (395, Figure 22), were purified from Lophiostoma sp. Eef-7 is associated with Eucalyptus exserta. Compounds 394 and 395 displayed poor antibacterial activity against Ralstonia solanacearum with 9.86 and 9.58 mm zones of inhibition when 64 µg was added (positive control was streptomycin sulfate with a 13.03 mm zone of inhibition at an added amount of 6.25 µg) [171].

Two new cytochalasan alkaloids, cytochrysins A and C (396 and 397, Figure 22), were isolated from Cytospora chrysosperma, an endophytic fungus isolated from Hippophae rhamnoides. Compound 396 showed significant antibacterial activity against multi-drug resistant Enterococcus faecium with MIC value of 25 μg/mL, and compound 397 was active against MRSA with a MIC value of 25 μg/mL [172].

Two known α-pyridones, (8R,9S)-dihydroisoflavipucine (398) and (8S,9S)-dihydroisoflavipucine (399, Figure 22) were isolated from Lophiostoma sp. Sigrf10 is associated with Siraitia grosvenorii. Compounds 398 and 399 were active against B. subtilis, A. tumefaciens, R. solanacearum, and X. vesicatoria, with IC₅₀ values in the range of 35.68–44.85 µM [173].

Microsphaerol (400), a novel polychlorinated triphenyl diether was extracted from Microsphaeropsis sp and seimatorone (401, Figure 22), a new naphthalene derivative, was purified from the endophyte Seimatosporium sp. Compound 400 displayed potent antibacterial activity against B. megaterium and E. coli, with 8 and 9 mm zones of inhibition at 0.05 mg concentration (50 mL of 1 mg/mL). Compound 401 exhibited moderate antibacterial activity against B. megaterium and E. coli, with 3 and 7 (partial inhibition) mm zones of inhibition at a 0.05 mg concentration (50 mL of 1 mg/mL) [174].

Known compounds epicocconigrone A (402), epipyrone A (403), and epicoccolide B (404, Figure 22) were purified from Epicoccum nigrum MK214079 associated with Salix sp. Compounds 402–404 exhibited moderate activity against S. aureus, with MICs ranging from 25 to 50 μM [175].

The known compounds p-hydroxybenzaldehyde (223), indole-3-carboxylic acid (405) and quinizarin (406, Figure 22) and beauvericin (267), were isolated from Epicoccum nigrum associated with the Entada abyssinica. Compound 267 displayed activity against S. aureus, B. cereus, and Salmonella typhimurium, with MIC values of 3.12, 12.5, and 12.5 µg/mL. Compounnd (223) displayed activity against S. aureus, B. cereus, P. aeruginosa, and E. coli with MIC values of 50, 25, 50, and 25 µg/ml. Compound 405 was found to be active against S. aureus and E. faecalis (MICs of 6.25 and 50 µg/mL) while compound 406 displayed activity against S. aureus, B. cereus St (MICs of 50 µg/mL each) [176].

The endophytic fungus Stemphylium lycopersici from S. tonkinensis yielded xylapeptide B (407), cytochalasin E (408), 6-heptanoyl-4-methoxy-2H-pyran2-one (409) and (–)-5-carboxymellein (410, Figure 22). Compound 407 showed average inhibition against B. subtilis with a MIC value of 12.5 μg/mL, and against S. aureus and E. coli with MIC values of 25 μg/mL. Compound 408 inhibited B. subtilis, S. aureus, B. anthracis, S. dysenteriae, and E. coli with MIC values ranging from 12.5 to 25 μg/mL. Compound 409 inhibited S. paratyphi B with MIC value of 12.5 μg/mL. Compound 410 inhibited B. subtilis, S. aureus, B. anthracis, S. dysenteriae, S. paratyphi, E. coli and S. paratyphi B with MIC values ranging from 12.5 to 25 μg/mL [177].

A new tetrahydroanthraquinone derivative, dihydroaltersolanol C (411, Figure 22) was purified from Stemphylium globuliferum residing inside the plant Juncus acutus. Compound 411 exhibited moderate growth inhibition effects against S. aureus with a MIC of 49.7 μM [178].

An endophytic fungus Lecanicillium sp. (BSNB-SG3.7 Strain) associated with Sandwithia guyanensis yielded stephensiolides I (412), D (413), G (414), and stephensiolide F (415, Figure 22). Compounds 412–415 displayed anti-MRSA activity with MIC values of 4, 32, 16 and 32 μg/mL, respectively [179].

The compound phomalactone (416, Figure 23) was isolated from the endophyte Nigrospora sphaerica associated with Adiantum philippense. Compound 416 displayed good antibacterial activity against E. coli and X. campestris with MIC values of 3.12 μg/mL and moderate activity against S. typhi, B. subtilis, B. cereus, and K. pneumonia with a MIC value of 6.25 μg/mL. A MIC of 12.5 μg/mL was found against S. aureus, and S. epidermidis [180].

A new naturally occurring compound, nigrosporone B (417, Figure 23), was purified from Nigrospora sp. BCC 47789 associated with the leaves of Choerospondias axillaris. Compound 417 exhibited antibacterial activity against M. tuberculosis, B. cereus and E. faecium with MIC values of 172.25, 21.53 and 10.78 μM, respectively [181].

Two bioactive compounds, 2′-deoxyribolactone (418) and hexylitaconic acid (419, Figure 23) were purified from Curvularia sorghina BRIP 15900 associated with the stem bark of Rauwolfia macrophylla. Compounds 418 and 419 inhibited Staphylococcus warneri E. coli, Pseudomonas agarici and Micrococcus luteus, with MICs ranging between 0.17 μg/mL and 0.58 μg/mL [182].

Known compounds, namely the triticones E (420) and F (421, Figure 23), were purified from Curvularia lunata, isolated from healthy capitula of Paepalanthus chiquitensis. Compounds 420 and 421 showed good antibacterial activity for E. coli, with MIC values of 62.5 μg/mL [183].

The known compounds cochlioquinones B (422), C (423), and isocochlioquinone C (424, Figure 23) were purified from Bipolaris sp. L1-2 which is associated with the leaves of Lycium barbarum. Compounds 422–424 showed antimicrobial activity against B. subtilis, C. perfringens, and P. viridiflava, with MICs of 26 μM [184].

A new previously undescribed chromone, (S)-5-hydroxyl-2-(1-hydroxyethyl)-7-methylchromone (425) and the known sativene-type sesquiterpenoid 5,7-dihydroxy-2,6,8-trimethylchromone (426, Figure 23), were purified from Bipolaris eleusines associated with potatoes from Yunnan Agricultural University (Kunming, Yunnan, China). Compounds 425 and 426 displayed poor inhibitory activities against S. aureus sub sp. aureus with the inhibition rates of 56.3 and 32 %, respectively, at the concentration of 128 μg/mL (penicillin G: 99.9% at 5 μg/mL) [185].

Two new diketopiperazines, bionectin D (427) and bionectin E (428) and the known compounds verticillin A (429) sch 52901 (430) and gliocladicillin C (431, Figure 23) were purified from Bionectria sp. Y1085, isolated from Huperzia serrata. Bionectin D (427) is a rare diketopiperazine with a single methylthio substitution at the α-carbon of a cyclized amino acid residue. Compounds 427–331 exhibited antibacterial activity against E. coli, S. aureus, and S. typhimurium, with MIC values ranging from 6.25–25 µg/mL [186].

Known compounds pyrrocidine A (432) and 19-O-methylpyrrocidine B (433, Figure 23) were extracted from the endophytic fungus, Cylindrocarpon sp., isolated from Sapium ellipticum. Compound 433 exhibited moderate antibacterial activity against S. aureus ATCC 25923 and ATCC 700699 with MIC values of 50 and 25 μM, respectively. Compound 432 showed strong to moderate inhibitory effects against S. aureus strain ATCC 25923 and ATCC 700699, E. faecalis strain ATCC 29212 and ATCC 51299, E. faecium strain ATCC 35667 and ATCC 700221 with MIC values ranging from 0.78 to 25 μM [187].

Two new decalin-containing compounds, eupenicinicols C (434), and D (435, Figure 23), along with two biosynthetically-related known metabolites, eujavanicol A (436), and eupenicinicol A (437, Figure 24) were obtained from Eupenicillium sp. LG41.9 (now considered as Penicillium) residing inside the roots of Xanthium sibiricum when treated with the HDAC inhibitor nicotinamide (15 mg/100 mL). Compound 435 exhibited pronounced efficacy against S. aureus with a MIC of 0.1 μg/mL, and compound 436, was active against E. coli with a MIC of 5.0 μg/mL [188].

A new anthranilic acid derivative, 2-phenylethyl 3-hydroxyanthranilate (438) and 2-phenylethyl anthranilate (439, Figure 24) were extracted from Dendrothyrium variisporum extracted from the roots of Globularia alypum. Metabolite 438 was found to be active against B. subtilis and M. luteus (MICs of 8.33 and 16.66 μg/mL). Compound 439 showed potent activity against B. subtilis and S. aureus with MIC values of 66.67 μg/mL each [189].

Ravenelin (440, Figure 24) was extracted from Exserohilum rostratum, an endophyte of Phanera splendens, an endemic medicinal plant of the Amazon region. Ravenelin (440) displayed antibacterial activity against B. subtilis and S. aureus with MIC values of 7.5 and 484 μM, respectively (amoxicillin MIC against B. subtilis and S. aureus 1.3 and 21.4 μM; another positive control terramycin MIC against B. subtilis and S. aureus 16.3 and 16.3 μM, respectively) [190].

The compounds monocerin (441), annularin I (442), and annularin J (443, Figure 24) were purified from Exserohilum rostratum isolated from Bauhinia guianensis. Compound 441 displayed antibacterial activity with MIC values of 62.5 µg/mL against P. aeruginosa. Compound 442 exhibited antibacterial activity with MIC values of 62.50 and 31.25 µg/mL against E. coli and B. subtilis, respectively. Compound 443 displayed weak activity against E. coli and B. subtilis with MIC values of 62.50 µg/mL each [191].

2.3. Basidiomycetes

The compounds quercetin (444), carboxybenzene (445), and nicotinamide (446, Figure 24) were purified from Psathyrella candolleana residing inside the seeds of Ginkgo biloba. Compounds 444–446 have antibacterial activity against S. aureus (MIC 0.3906, 0.7812 and 6.25 μg/mL) [192].

A new tremulane sesquiterpene, irpexlacte A (447), and three new furan derivatives, irpexlactes B-D (448–450, Figure 24), were isolated from the endophytic fungus Irpex lacteus DR10-1 of the waterlogging-tolerant plant Distylium chinense. Compounds 447–450 showed moderate antibacterial activity against P. aeruginosa with MIC values ranging from 23.8 to 35.4 μM [193].

2.4. Zygomycetes

A flavonoid compound, chlorflavonin (451, Figure 24) was purified from the endophytic fungus Mucor irregularis, isolated from Moringa stenopetala. It has shown antibacterial activity (MIC₉₀) against M. tuberculosis at a 1.56 μM concentration. Chlorflavonin also had shown synergistic effects with isoniazid and delamanid in combination treatment experiments. Various molecular and docking techniques have shown that chlorflavonin interacts with the acetohydroxyacid synthase catalytic subunit IlvB1 and inhibits their activity. Recently, Rehberg et al. [194] found the antimicrobial activity of chlorflavonin (451) to be higher in comparison to streptomycin treatment against macrophages infected with M. tuberculosis.

3. Volatile Organic Compounds (VOCs)

Volatile organic compounds (VOCs) are chemical entities which have low molecular weights and typically evaporate or get into the vapor phase at normal temperature and pressure. They generally possess a characteristic odor [195]. Several reviews have emphasized the production of biogenic VOCs as possible signal molecules in the course of interaction with a host or that play a role in the process of host integration. At times they are also identified as indicators of fungal growth [196,197,198]. Fungal VOCs largely comprise aliphatic as well as aromatic hydrocarbons, aldehydes, mono-, di- and sesquiterpenes, esters and ketones. Some of the interesting aspects of fungal volatiles is their possible role during interactions among the microbes i.e., with bacteria as well as fungi. However, the application of fungal VOCs as an arsenal to kill bacteria and fungi has not been extensively explored.

The discovery of the endophytic fungus Muscodor albus Cz 620 which exhibited potent antibiotic type activity, wiping out all the microbes in its vicinity was serendipitous. This was attributed due to the volatile cocktail produced by Muscodor albus Cz 620. This marked the beginning of the exploration of fungal endophytes with the potential to produce volatile antibiotics. The genus Muscodor has expanded in the last two decades owing to the addition of novel members that were largely based on the chemical signatures and genetic profiles. Presently there are ~22 known type species that have been documented [199]. Uniquely, all the species of Muscodor reported to date are sterile in nature and exhibit a characteristic spectrum of antibacterial as well as anti-fungal activities largely driven by the chemical composition of their volatile gas mixtures. It has also been shown that a single component of the volatile gas is unable to mimic the anti-microbial action suggesting it to be a synergistic action of the finely tuned composition of different VOCs [200]. The pharmaceutical importance of the VOCs produced by Muscodor species was exemplified by the anti-bacterial and anti-fungal potential of the VOCs emitted by the fungus. VOCs of Muscodor albus Cz620 inhibited E. coli and Bacillus subtilis while only E. coli was inhibited in the presence of volatiles of other isolates of Muscodor albus viz. KN-26, KN-27, GP-100, GP-115, TP-21, which inhibited only E. coli [201]. The volatiles of M. albus I-41.3s on the other hand inhibited Bacillus subtilis, E. coli, and Salmonella typhi. All the VOC emissions were predominantly bacteriostatic and not bactericidal [202].

Muscodor crispans (B-23) has a characteristic VOC spectrum which exhibited anti-mycobacterial activity i.e., against Mycobacterium marianum apart from S. aureus ATCC6538, Salmonella cholereasus, and Yersinia pestis [203]. Muscodor fengyangensis exclusively inhibited E. coli [204]. The volatiles produced by Muscodor kashayum has a potent bactericidal activity towards E. coli, Pseudomonas aeruginosa, Salmonella typhi and S. aureus [205]. Four isolates of Muscodor reported from Southeast Asia, viz. M. oryzae, M. musae, M. suthepensis and M. equisetii, exerted bactericidal activity against Enterococcus faecalis, E. coli, Proteus mirabilis, S. aureus and Pseudomonas pneumoniae [206]. The VOCs of Muscodor have also inspired development of a veterinary medicine formulation which is used as an anti-diarrhoeal product. The formulation is called Sx calf, that is currently being produced and marketed by Ecoplanet Environment LLC (Belgrade, MT, USA) [207]. Similarly, the volatiles of Muscodor cinnamomi was found to be effective against Staphylococcal spp., Salmonella sp., E. coli, Klebsiella spp., Streptococcus spp. and Enterococcus species which contaminate eggs thereby not only affecting their shelf life but also making them unfit for human consumption [208]. The volatile cocktail of Muscodor crispans (B-23) was found to kill the bacterial pathogen of citrus Xanthomonas axonopodis pv. citri [203].

The introspection of the spectrum of the volatile organic mixture from different Muscodor species has revealed the antibacterial spectrum of some commonly occurring entities such as isobutyric acid [209,210,211], β-bisabolol and azulene and its derivatives [212]. Thus, creating artificial mixtures and evaluating them for their anti-bacterial activities may prove to be very useful for preventing drug-resistant film-forming bacteria from causing infections in clinical as well as non-clinical settings. Hence the present study, opens avenues to explore higher numbers of fungal endophytes for their unique volatile signatures and assess them for anti-bacterial activities for developing interventions that could check the spread and infections caused by the drug-resistant bacteria by using them in volatile form or as gaseous sprays.

Table 1. Anti-bacterial metabolites reported from endophytic fungi.

Sr. No.	Fungus	Source	Locality	Compounds Isolated	Biological Target	Biological Activity (MIC/IC50/ID50)	Reference
Ascomycetes
Diaporthe
1	Diaporthe sp.	Uncaria gambier		(+)-1,1′-Bislunatin (1) and (+)-2,2′- epicytoskyrin A (2)	Mycobacterium tuberculosis strains H37Rv	MICs 0.422 and 0.844 μM	[18]
2	Diaporthe sp. GDG-118	Sophora tonkinensis	Hechi City, China	21-Acetoxycytochalasin J3 (3)	Bacillus anthraci and E. coli	inhibited at 12.5 μg/mL concentration	[19]
3	Phomopsis fukushii.			1-(3-Hydroxy-1-(hydroxymethyl)-2-methoxy-6-methylnaphthalen-7-yl) propan-2-one (4) and 1-(3-hydroxy-1- (hydroxymethyl)-6-methylnaphthalen-7-yl)propan-2-one (5)	MRSA	Zone of inhibition of 10.2 and 11.3 mm (6 mm strile filterpaper disc were impregnated with 20µL (50 µg) of each compound)	[20]
4	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	3-Hydroxy-1-(1,8- dihydroxy- 3,6-dimethoxynaphthalen-2-yl)propan-1-one (6), 3-hydroxy-1-(1,3,8-trihydroxy-6-methoxynaphthalen-2-yl)propan-1-one (7) and 3-hydroxy-1-(1,8-dihydroxy3,5-dimethoxynaphthalen-2-yl) propan-1-one (8)	MRSA- ZR11	MIC, 8, 4, and 4 µg/mL,	[21]
5	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	1-[2-Methoxy-4-(3-methoxy-5-methylphenoxy)-6-methylphenyl]-ethanone (9) and 1-[4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6-methylphenyl]-ethanone (10)	MRSA	Zone of inhibition 13.8 and 14.6 mm	[22]
6	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, P. R. China	4-(3-Methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (11), 4-(3-Hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (12) and 4-(3-methoxy-5-methylphenoxy)-2-(3-hydroxypropyl) -6-methylphenol (13)	MRSA	Zone of inhibition of 20.2, 17.9 and 15.2 mm (tested at 50µg/6 mm disc)	[23]
7	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China.	1-(4-(3-Methoxy-5-methylphenoxy)-2-methoxy-6-methylphenyl)-3-methylbut-3-en-2-one (14), 1-(4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6- methylphenyl)-3-methylbut-3-en-2-one (15), 1-(4-(3-hydroxy-5-(hydroxymethyl)phenoxy)-2-methoxy-6- methylphenyl)-3-methylbut-3-en-2-one (16)	MRSA	Zone of inhibition of 21.8, 16.8 and 15.6 mm, (50 µg/6 mm disc)	[24]
8	Phomopsis sp.	-	-	3-Hydroxy-6-hydroxymethyl-2,5-dimethylanthraquinone (17), 6-hydroxymethyl-3-methoxy-2,5-dimethylanthraquinone (18)	MRSA	IZD 14.2 and 14.8 mm	[25]
9	Diaporthe sp.	Pteroceltis tatarinowii	Mufu Mountain of Nanjing, China.	Diaporone A (19)	B. subtilis	MIC, 66.7 μM,	[26]
10	Phomopsis prunorum (F4-3).	-	-	(−)-1 and (+)- Phomoterpenes A and B (20) phomoisocoumarins C (21), D (22)	X. citri pv. phaseoli var. fuscans	MIC, 31.2, 62.4, 31.2, and 31.2 μg/mL,	[27]
					Pseudomonas syringae pv. Lachrymans	MIC, 31.2, 15.6, 31.2 and 15.6 μg/mL
11	Diporthe vochysiae LGMF1583	Vochysia divergens	-	Vochysiamides A (23)	KPC (Klebsiella pneumoniae carbapenemase producing).	MIC, 1.0 μg/mL	[28]
				Vochysiamides B (24)	KPC, MSSA, MRSA	MIC, 0.08, 1.0, and 1.0 µg/mL
12	Phomopsis asparagi	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	4-(3-Methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)- 6-(hydroxymethyl)phenol (25), 4-(3-Hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-(hydroxymethyl)phenol(26)	MRSA	Zone of inhibition of 10.8 and 11.4 mm	[29]
13	Phomopsis sp.	Paris polyphylla var. yunnanensis	ShiZhong, Yunnan, China	5-Methoxy-2-methyl-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (27), 2-(hydroxymethyl)-5-methoxy-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (28)	MRSA	Zone of inhibition of 14.5 and 15.2 mm	[30]
14	Diaporthe terebinthifolii LGMF907	Schinus terebinthifolius	Curitiba, Paraná, Brazil	Diaporthin (29)	E. coli, Micrococcus luteus, MRSA, and S. aureus	Zone of inhibition 1.73, 2.47, 9.50, and 9.0 mm tested at 100 μg/disk.	[31]
				Orthosporin (30)		Zone of inhibition of 1.03, 1.53C, 9.0, and 9.33 mm
15	Phomopsis/Diaporthe sp. GJJM 16	Vitex negundo	Azhiyar, Pollachi, Tamilnadu, India	(2Z)-2-(1,4-dihydro-2-hydroxy-1-((E)-2-mercapto-1 (methylimino)ethyl) pyrimidine-4-ylimino)-1-(4,5-dihydro-5-methylfuran-3-yl)-3-methylbutane-1-one (31)	S. aureus, and P. aeroginosa	MIC of 1.25 μg/mL against each organism	[32]
16	Phomopsis sp. PSU-H188	Hevea brasiliensis	Trang Province, Thailand.	Diaporthalasin (32)	S. aureus ATCC25923, MRSA	MIC, 4 μg/mL each	[33]
				Cytosporone B (33)		MIC, 32 and 16 μg/mL
				Cytosporone D (34)		MIC, 64 and 32 μg/mL
17	Diaporthe terebinthifolii GG3F6	Glycyrrhiza glabra	Jammu, J & K, India	Diapolic acid A (35), B (36) xylarolide (37) phomolide G (38)	Yersinia enterocolitica	IC50, 78.4, 73.4, 72.1 and 69.2 μM	[34]
18	Diaporthe sp. F2934	leaves of Siparuna gesnerioides	Chagres National Park, a protected area of Panama	Phomosine A (39)	S. aureus (ATCC 25923), Streptococcus oralis (ATTC 35037), Enterococcus faecalis (ATCC 19433), Enterococcus cloacae (ATCC 13047), Bordetella bronchiseptica (CECT 440),	Zone of Inhibition 12, 9, 10, 11, 10 and 10 mm at 4 µg/mL concentration	[35]
				Phomosine C (40)		Zone of Inhibition 9, 6, 8, 8, 8 and 9 mm at 4 µg/mL concentration
19	Phomopsis sp.,	Garcinia kola nuts	bought at Mokolo local market in Yaounde (Cameroon)	18-Methoxycytochalasin J (41), cytochalasins H (42) and J (43), alternariol (44)	Shigella flexneri	MIC, 128 μg/mL each	[36]
				18-Methoxycytochalasin J (41), cytochalasins H (42)	S. aureus ATCC 25923	MIC, 128 and 256 μg/mL
20	Diaporthe sp. LG23	Mahonia fortunei	Shanghai, China	19-nor-Lanosta-5(10),6,8,24-tetraene-1α,3β,12β,22S-tetraol (45)	S. aureus, E. coli, Bacillus subtilis, P. aeruginosa, Streptococcus pyogenes	MIC, 5.0, 5.0, 2.0, 2.0 and 0.1 µg/mL	[37]
				3β,5α,9α-Trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (46), and chaxine C (47)	B. subtilis	MIC, 5.0 µg/mL each
21	Diaporthales sp. E6927E	Ficus sphenophyllum	Ecuadorean dry forest near the Napo River, USA	Pyrrolocin A (48)	S. aureus and E. faecalis	MICs 4 and 5 µg/mL	[38]
	Xylaria
22	Xylaria ellisii	Blueberry (Vaccinium angustifolium)		Ellisiiamide (49)	Escherichia coli	MIC, 100 μg/mL	[39]
23	Xylaria sp. GDG-102	S. tonkinensis	Hechi, Guangxi province, China	Xylareremophil (50)	Micrococcus luteus and Proteus vulgaris	MIC 25 μg/mL each	[40]
				Mairetolides B (51)	M. luteus	MIC, 50 μg/mL
				Mairetolide G (52)	P. vulgaris M. luteus	MIC 25 and 50 μg/mL
				Xylareremophil (50), mairetolides B (51), and G (52)	Micrococcus lysodeikticus and Bacillus subtilis	MIC 100 μg/mL
24	Xylaria sp. (GDG-102)	Leaves of S. tonkinensis		6-Heptanoyl-4-methoxy-2H-pyran-2-one (53)	E. coli as well as S. aureus	MIC, 50 μg/mL	[41]
25	Xylaria sp. GDG-102	S. tonkinensis	Hechi, Guangxi province, China	Xylarphthalide A (54)	B. subtilis and E. coli,	MIC, 12.5 μg/mL each	[42]
					B. megaterium, S. aureus, S. dysenteriae and S. paratyphi	MIC, 25 μg/mL each
				(−)-5-Carboxymellein (55)	B. Subtilis	MIC, 12.5 μg/mL
					B. anthracis, B. megaterium, S. aureus, E. coli, S. dysenteriae and S. paratyphi B	MIC, 25 μg/mL
				(−)-5-Methylmellein (56)	B. subtilis and S. aureus	MIC, 12.5 μg/mL
					B. megaterium, E. coli and S. dysenteriae	25 μg/mL
26	Xylaria sp.,	Taxus mairei.		3,7-Dimethyl-9-(-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl) nona-1,6-dien-3-ol (57)	B. subtilis ATCC 9372, B. pumilus 7061 and S. aureus ATCC 25923	48.1, 31.6 and 47.1% inhibition.	[43]
				Nalgiovensin (58)	S. aureus ATCC 25923, B. subtilis ATCC 9372, B. pumilus ATCC 7061 and E. coli ATCC 25922	42.1, 36.8, 47.1 and 41.2% inhibition.
	Chaetomium
27	C. globosum 7s-1,	Rhapis cochinchinensis		Xanthoquinodin B9 (59), xanthoquinodin A1 (60), xanthoquinodin A3 (61)	B. cereus	MICs of 0.87, 0.44 and 0.22 μM,	[45]
				Xanthoquinodin B9 (59), xanthoquinodin A1 (60), xanthoquinodin A3 (61)	S. aureus and MRSA	MIC values ranging from 0.87 to 1.75 μM
				3-Epipolythiodioxopiperazines, chetomin (62), chaetocochin C (63) and dethio-tetra(methylthio)chetomin (64)	B. cereus ATCC 11778, S. aureus ATCC 6538, and MRSA	MIC values ranging from 0.02 pM to 10.81 μM.
				Chetomin (62)	B. cereus, S. aureus and MRSA	MICs, 0.35 μM, 10.74 and 0.02 pM
				Compounds 59–64	E. coli ATCC 25922, P. aeruginosa ATCC 27853, and Salmonella typhimurium ATCC 13311	MICs of 45.06 to >223.72 μM
				Epipolythiodioxopiperazines (62–64)	Mycobacterium tuberculosis	MICs, 0.55, 4.06 and 8.11 μM,
28	Chaetomium sp. SYP-F7950	Panax notoginseng	Wenshan, Yunnan, China	Chaetocochin C (63), chetomin A (65), and chetomin (62)	S. aureus, B. subtilis, Enterococcus faecium	MIC values ranging from 0.12 to 19.3 μg/mL	[46]
29	Chaetomium sp. HQ-1,	Astragalus chinensis	Tai’an, Shandong Province, China	Differanisole A (66)	L. monocytogenes S. aureus and MRSA,	MIC, 16, 128, 128 μg/mL	[47]
				2,6-Dichloro-4-propylphenol (67), 4,5-dimethylresorcinol (68)	L. monocytogenes	MICs of 64 and 32 μg/mL,
30	Chaetomium nigricolor F5,	Mahonia fortune	Qingdao, People’s Republic of China	Chamiside A (69)	S. aureus	MIC of 25 μg/mL	[48]
31	C. globosum	Salvia miltiorrhiza	Shenyang, Liaoning province, China	Equisetin (70)	Multidrug-resistant E. faecalis, E. faecium, S. aureus, and S. epidermidis	MIC values of 3.13, 6.25, 3.13, and 6.25 μg/mL	[49]
32	Chaetomium sp. Eef-10,	Eucalyptus exserta	Guangdong Province, China	Mollicellins H (71)	S. aureus ATCC29213, S. aureus N50, MRSA,	IC50, 5.14, and 6.21 μg/mL	[50]
				Mollicellin O (72)	S. aureus ATCC29213 and S. aureus N50	IC50, 79.44 and 76.35 μg/mL
				Mollicellin I (73)		IC50, 70.14 and 63.15 μg/mL
33	Chaetomium sp. M336	Huperzia serrata	Xichou County, Yunnan Province, China	6-Formamidochetomin (74)	E. coli, S. aureus, S. typhimurium ATCC 6539 and E. faecalis	MIC, 0.78 μg/mL	[51]
34	Chaetomium globosum	Nymphaea nouchali	Udugampola in the Gampaha District, Sri Lanka	Chaetoglobosin A (75)	B. subtilis, S. aureus, and MRSA	MIC, 16, 32 and 32 μg/mL	[52]
				Chaetoglobosin B (76)		>64 μg/mL
	Talaromyces
35	Talaromyces pinophilus XL-1193	Salvia miltiorrhiza	Shenyang, Liaoning province, China	Pinophol A (77)	Bacterium paratyphosum B	MIC, 50μg/mL	[53]
36	Talaromyces purpureogenus XL-25	Panax notoginseng	Shijiazhuang, Hebei Province, China	Talaroconvolutin A (78)	B. subtilis Micrococcus lysodeikticus, Vibrio parahaemolyticus	MIC value of 1.56 μM	[54]
				Talaroconvolutin B (79)		MIC = 0.73 and 0.18 μM
37	Talaromyces purpureogenus	Panax notoginseng		(1S,5S,7S,10S)-dihydroxyconfertifolin (80)	E. coli	MIC, 25 μM	[55]
38	Talaromyces funiculosus -Salicorn 58.			Talafun (81)	E. coli, S. aureus	MIC, 18 and 93 μM	[56]
				N-(2′-hydroxy-3′-octadecenoyl)-9-methyl-4,8-sphingadienin (82)	Mycobacterium smegmatis, S. aureus, Micrococcus tetragenus, and E. coli	MIC, 85, 90, 24, and 68, 93 μM
				Chrodrimanin A (83)	S. aureus, M. tetragenus, Mycobacterium phlei, and E. coli	MIC, 67, 28, 47, and 26 μM
				Chrodrimanin B (84)	E.coli	MIC, 43 μM.
39	Talaromyces sp. LGT-2	Tripterygium wilfordii.		Alkaloids 85–90	E. coli, P. aeruginosa, S. aureus, Bnfillus licheniformis, and Streptococcus pneumoniae	MICs in the range of 0.125 to 1.0 50 μg/mL	[57]
40	Rhytidhysteron sp. BZM-9	Leptospermum brachyandrum		Euphorbol (91)	MRSA	MIC, 62.5 ug/mL	[58]
41	Stagonosporopsis oculihominis	Dendrobium huoshanense.		Stagonosporopsin C (92)	Staphylococcus aureus subsp. aureus ATCC29213	MIC50, 41.3 μM	[59]
42	Eutypella scoparia SCBG-8.	Leptospermum brachyandrum	SCBG, Chinese Academy of Sciences, China	Eutyscoparols H (93), I (94), tetrahydroauroglaucin (95), flavoglaucin (96)	Staphylococcus aureus and MRSA	MICs in the range of 1.25 to 6.25 μg/mL	[60]
43	Eutypella scoparia SCBG-8	Leptospermum brachyandrum	SCBG, Chinese Academy of Sciences, Guangzhou 510650, China	Eutyscoparin G (97)	S. aureus and MRSA	MIC values of 6.3 μg/mL	[61]
44	Sarocladium oryzae DX-THL3,	Oryza rufipogon Griff.		Sarocladilactone A (98), sarocladilactone B (99), helvolic acid (100), helvolinic acid (101), 6- desacetoxy-helvolic acid (102), 1,2-dihydrohelvolic acid (103)	S. aureus	MIC values of 64, 4, 8, 1, 4 and 16 μg/mL	[62]
				Compound 101	B. subtilis	MIC, 64 μg/mL
				Compounds 99, 101, 103	E. coli	MIC 64 μg/mL each
45	Paraphaeosphaeria sporulosa	Fragaria x ananassa	Caserta province, Southern Italy	Cyclo(L-Pro-L-Phe) (104)	Salmonella strains, S1 and S2	MIC 71.3 and 78.6 μg/mL	[63]
46	Aplosporella javeedii	Orychophragmus violaceus	Beijing, China	Terpestacin (105), fusaproliferin (106), mutolide (108)	M. tuberculosis H37Rv	MICs of 100 μM	[64]
				6,7,9,10-Tetrahydromutolide (107)	S. aureus,	MICs of 100 μM
47	Pleosporales sp. Sigrf05	roots of Siraitia grosvenorii	Guangxi Province of China	Pleospyrone E (109)	B. subtilis, Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas vesicatoria	MIC 100.0µM each	[65]
48	Aplosporella javeedii	Orychophragmus violaceus	Beijing, China	Aplojaveediin A (110)	Staphylococcus aureus strain ATCC 29213, S. aureus strain ATCC 700699 and Bacillus subtilis (ATCC 169)	MICs 50, 50 and 25 μM,	[66]
				Aplojaveediin F (111)	S. aureus ATCC 29213 and ATCC 700699	MICs of 25 and 50 μM
49	Paecilomyces variotii	Lawsonia Alba	University of Karachi, Pakistan	Lawsozaheer (112)	S. aureus (NCTC 6571)	84.26% inhibition at 150 μg/mL	[67]
50	Preussia isomera OSMAC strategy	Panax notoginseng	Wenshan, Yunnan Province, China	Setosol (113)	Multidrug-resistant E. faecium, methicinllin-resistant S. aureus and multidrug-resistant E. faecalis	MIC 25 μg/mL	[68]
	Preussia isomera. XL-1326,	Panax notoginseng		(+)- and (−)-Preuisolactone A (114, 115)	Micrococcus luteus and B. megaterium	MIC, 10.2 and 163.4 μM	[69]
51	Neurospora udagawae	Quercus macranthera	Kaleybar region in northwestern Iran	Udagawanones A (116)	S. aureus	MIC, 66 μg/mL	[70]
52	Xylomelasma sp. Samif07	Salvia miltiorrhiza Bunge		2,6-Dimethyl-5-methoxy-7-hydroxychromone (117), 6-hydroxymethyleugenin (118), 6-methoxymethyleugenin (119), isoeugenitol (120), diaporthin (29), 8-hydroxy-6-methoxy-3-methylisocoumarin (121)	Bacillus subtilis, Staphylococcus haemolyticus, A. tumefaciens, Erwinia carotovora, and Xanthomonas vesicatoria	MIC values at the range of 25 ~ 100 μg/mL	[71]
				2,6-Dimethyl-5-methoxy-7-hydroxychromone (117), diaporthin (29)	B. subtilis, E. carotovora	MIC, 50 and 100 μg/mL
				6-Hydroxymethyleugenin (118), 6-methoxymethyleugenin (119), isoeugenitol (120), diaporthin (29)	S. haemolyticus and E. carotovora	MIC, 75 μg/mL each
				8-Hydroxy-6-methoxy-3-methylisocoumarin (121)	B. subtilis, A. tumefaciens, and X. vesicatoria,	MICs 25, 75, and 25 μg/mL,
53	Amphirosellinia nigrosporaJS-1675	Pteris cretica		(4S,5S,6S)-5,6-epoxy-4-hydroxy-3-methoxy-5-methylcyclohex-2-en-1-one (122)	Acidovorax avenae subsp. cattlyae, Agrobacterium konjaci, A. tumefaciens, Burkholderia glumae, Clavibacter michiganensis subsp. michiganensis, Pectobacterium carotovorum subsp. carotovorum, Pectobacterium chrysanthemi, Ralstonia solanacearum, Xanthomonas arboricola pv. pruni, Xanthomonas axonopodis pv. Citri, Xanthomonas euvesicatoria, Xanthomonas oryzae pv. oryzae	MICs ranging between 31.2 and 500 µg/ml	[72]
54	Emericella sp. XL029	Panax notoginseng		5-(Undeca-3′,5′,7′-trien-1′-yl)furan-2-ol (123) and 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-carbonate (124)	B. subtilis, B. cereus, S. aureus, B. paratyphosum B, S. typhi, P. aeruginosa, E. coli, and E. aerogenes	MIC values ranging from 6.3 to 50 μg/mL	[73]
56	Emericella sp. XL029	Panax notoginseng	Shijiazhuang, Hebei Province, China	14-Hydroxytajixanthone (125), 14- hydroxytajixanthone hydrate (126), 14- hydroxy-15-chlorotajixanthone hydrate (127), 14-methoxytajixanthone-25-acetate (130), questin (132), and carnemycin B (133)	M. luteus, S. aureus, B. megaterium, B. anthracis, and B. paratyphosum B	MIC, in the range of of 12.5 and 25μg/mL	[74]
				Epitajixanthone hydrate (128)	M. luteus, S. aureus, B. megaterium, and B. paratyphosum B	MIC 25 μg/mL
				Tajixanthone hydrate (129), 15-chlorotajixanthone hydrate (131)	S. aureus, B. megaterium, and B. paratyphosum B	MICs 25 and 12.5 μg/mL,
				14-Hydroxytajixanthone (125) Epitajixanthone hydrate (128), carnemycin B (133)	drug resistant S. aureus	MIC 50 μg/mL
				Compounds 125–133	P. aeruginosa, E. coli, and E. aerogenes	MIC 50 μg/mL
57	Byssochlamys spectabilis	Edgeworthia chrysantha	Hangzhou Bay, Hangzhou, Zhejiang Province, China	Bysspectin C (134)	E. coli ATCC 25922 and S. aureus ATCC 25923	MIC, 32 and 64 µg/mL	[75]
58	Poculum pseudosydowianum (TNS-F-57853),	Quercus crispula var. crispula	Yoshiwa, Hatsukaichi, Hiroshima prefecture, Japan	Sydowianumols A (135), and B (136)	MRSA	MIC90 values of 12.5 μg/mL	[76]
59	Lachnum palmae exposure to a HDAC inhibitor SAHA	Przewalskia tangutica	Linzhou Country of the Tibet Autonomous Region, China	Palmaerones A-B, E-G (137, 138, 140, 141, 142)	B. subtilis	MICs, 35, 30, 10, 50, and 55 μg/mL	[77]
				Palmaerones A-C, E (137, 138, 139, 140)	S. aureus	MICs 65, 55, 60, and 55, μg/mL
60	Nemania serpens	Vitis vinifera	Canada’s Niagara region	Nemanifuranone A (143)	E. coli	MIC 200 μg/mL	[78]
					S. aureus, B. subtilis and M. luteus	>75% inhibition at a concentration of 100–200 μg/mL
				Triterpenoid 144	S. cerevisiae	(>25% inhibition) against at 200 μg/mL
					M. luteus	(>75% inhibition) of at a concentration of 100 μg/mL
61	Paraconiothyrium variabile	Cephalotaxus harringtonia		Variabilone (145)	B. subtilis	IC50 of 2.13 μg/mL after 24 h (0.36 μg/mL for kanamycin)	[79]
62	Pyronema sp. (A2-1 & D1-2)	Taxus mairei	Shennongjia National Nature Reserve, Hubei province, China.	Methyl 2-{(E)-2-[4-(formyloxy)phenyl] ethenyl}-4-methyl-3-oxopentanoate (146), (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-perhydro-1,4-oxazine-2,5-dione (147), (3R,6R)-N-methyl-N-(1-hydroxy-2-methylpropyl)-phenylalanine (148), siccanol (149), fusaproliferin (106), and sambutoxin (150)	Mycobacterium marinum ATCCBAA-535,	IC50 of 64, 59, 57, 84, 43 and 32 μM, (positive control rifampin IC50 of 2.1 μM)	[80]
63	Pulvinula sp. 11120	Cupressus arizonica	Tucson, AZ, USA	Pulvinulin A (151), graminin C (152), cis-gregatin B (153), and graminin B (154)	E. coli	12, 18, 16 and14 mm zone of inhibition at 100 μg/mL	[81]
64	Stelliosphaera formicum	Duroia hirsuta	Yasuni’ National Park off the Napo River in Ecuador	Stelliosphaerols A (155) and B (156)	S. aureus	MIC values of 250 μg/mL	[82]
65	Unidentified Ascomycete	Melilotus dentatus		cis-4-Acetoxyoxymellein (157)	E. coli and B. megaterium	Zone of inhibition of 10 and 10 mm (Partial inhibition) at a concentration of 0.05 mg	[83]
				8-Deoxy-6-hydroxy-cis-4-acetoxyoxymellein (158)	E. coli and B. megaterium	Zone of inhibition of 9 and 9 mm (Partial inhibition) at a concentration of 0.05 mg
	Anamorphic Ascomycetes
	Aspergillus
66	Aspergillus sp. FT1307	Heliotropium sp.		Aspochalasin P (159), alatinone (160), β-11-methoxy curvularine (161), 12-keto-10,11-dehydrocurvularine (162)	S. aureus ATCC12600, B. subtilis ATCC6633 and MRSA ATCC43300	MIC in the range of 40 to 80 μg/mL	[84]
67	Aspergillus cristatus	Pinellia ternata		Aspergillone A (163)	B. subtilis and S. aureus	MIC50, 8.5 and 32.2 μg/mL	[85]
68	Aspergillus versicolor strain Eich.5.2.2	Eichhornia crassipes	El-Kanater El-Khayriah in Egypt	22S-Aniduquinolone A (164), 22R-aniduquinolone A (165)	S. aureus (ATCC700699)	MIC, 0.4 μg/mL	[86]
69	Aspergillus versicolor	roots of Pulicaria crispa	Saudi Arabia	Aspergillether B (166)	S. aureus, B. cereus, and E. coli	MICs, 4.3, 3.7, and 3.9 μg/mL	[87]
70	Aspergillus ochraceus SX-C7 eus SX-C7	Setaginella stauntoniana		3-O-β-D-Glucopyranosyl stigmasta-5(6),24(28)-diene (167)	Bacillus subtilis	MIC, 2 μg/mL	[88]
71	Aspergillus amstelodami (MK215708)	Ammi majus	Egypt	Dihydroauroglaucin (168)	E. coli, Streptococcus mutans, S. aureus	MIC, 1.95, 1.95 and 3.9 μg/mL	[89]
					S. aureus, E. coli, Streptococcus mutans, P. aeruginosa	Minimum biofilm inhibitory concentration (MBIC) = 7.81, 7.81, 15.63 and 31.25 μg/mL
72	Aspergillus micronesiensis	Phyllanthus glaucus	LuShan Mountain, Jiangxi Province, China	Cyschalasins A (169) and B (170)	MRSA	MIC50, 17.5 and 10.6 μg/mL: MIC90, 28.4 and 14.7 μg/mL	[90]
73	A. niger	Acanthus montanus	Kala Mountain neighborhood of Yaoundé, Africa	Methylsulochrin (171)	S. aureus, Enterobacter cloacae and Enterobacter aerogenes	MIC, 15.6, 7.8 and 7.8 μg/mL	[91]
74	Aspergillus tubingensis	stem of Decaisnea insignis	Qinling Mountain, Shaanxi Province, China	3-(5-Oxo-2,5-dihydrofuran-3-yl) propanoic acid (172)	Streptococcus lactis	MIC value of 32 μg/mL	[92]
75	Aspergillus flavipes Y-62	Suaeda glauca	Zhoushan coast, Zhejiang province, East China	Methyl 2-(4-hydroxybenzyl)-1,7-dihydroxy-6-(3-methylbut-2-enyl)-1H-indene-1-carboxylate (173)	MRSA	MIC, 128 μg/mL	[93]
					K. pneumoniae and P. aeruginosa	MIC, of 32 μg/mL each
76	Aspergillus sp.	Rhizome of Zingiber cassumunar		4-Amino-1-(1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl)-1H-1,2,3-triazole-5(4H)one (174)	Xanthomonas oryzae, Bacillus subtilis and E. coli	Zone of inhibition 37, 30 and 27 mm	[5]
				3,6-Dibenzyl-3,6-dimethylpiperazine-2,5-dione (175)	E. coli and X. oryzae	Zone of inhibition 21 and 16 mm.
77	Aspergillus fumigatus	Edgeworthia chrysantha	Hangzhou Bay (Hangzhou, China)	Pseurotin A (176), spirotryprostatin A (177)	S. aureus	MIC of 0.39 µg/mL each	[94]
				Spirotryprostatin A (177)	E. coli	MIC, 0.39 µg/mL
78	Aspergillus sp.,	Astragalus membranaceus		Fumiquinazoline J (178), fumiquinazoline C (180), fumiquinazoline H (181), fumiquinazoline D (182)	B. subtilis, S. aureus, E. coli and P. aeruginosa	MICs in the range of 0.5–8 μg/mL	[95]
				Fumiquinazoline I (179), fumiquinazoline B (183)		MICs in the range of 4–16 μg/mL
79	Aspergillus fumigatiaffnis	Tribulus terestris		(−)-Palitantin (184)	E. faecalis UW 2689 and Streptococcus pneumoniae	MIC, 64μg/mL	[96]
80	Aspergillus sp. TJ23	Hypericum perforatum (St John’ Wort)	Shennongjia areas of Hubei Province, China	Aspermerodione (185)	MRSA	MIC, 32 μg/mL/potential inhibitor of PBP2a	[97]
				Andiconin C (186)		marginal antimicrobial activity (>100μg/mL)
81	Aspergillus sp. YXf3	Ginkgo biloba		Prenylterphenyllin D (187), prenylterphenyllin E (188), 2′-O-Methylprenylterphenyllin (189), prenylterphenyllin (190)	X. oryzae pv. oryzicola Swings and E. amylovora	MIC, 20 μg/mL each	[98]
				Prenylterphenyllin B (191)	E. amylovora	MIC, 10 μg/mL
82	Aspergillus sp.	Pinellia ternata	Nanjing, Jiangsu Province, China	Aspergillussanone D (192)	P. aeruginosa, and S. aureus	MIC50, 38.47 and 29.91 μg/mL	[99]
				Aspergillussanone E (193)	E. coli	MIC50, 7.83 μg/mL
				Aspergillussanone F (194)	P. aeruginosa, and S. aureus	MIC50, 26.56, 3.93 and 16.48 μg/mL
				Aspergillussanone G (195)	P. aeruginosa, and S. aureus,	MIC50, 24.46 and 34.66 μg/mL
				Aspergillussanone H (196)	P. aeruginosa, and E. coli,	MIC50, 8.59 and 5.87 μg/mL
				Aspergillussanone I (197)	P. aeruginosa,	MIC50, 12.0 μg/mL
				Aspergillussanone J (198)	P. aeruginosa, E. coli and S. aureus	MIC50, 28.50, 5.34 and 29.87 μg/mL
				Aspergillussanone K (199)	P. aeruginosa, and S. aureus,	MIC50, 6.55 and 21.02 μg/mL
				Aspergillussanone L (200)	P. aeruginosa, S. aureus, and B. subtilis	MIC50, 1.87, 2.77, and 4.80 μg/mL,
				Compound 201	P. aeruginosa, and E. coli,	MIC50, 19.07 and 1.88 μg/mL
83	Aspergillus terreus JAS-2	Achyranthus aspera	Varanasi, India	Terrein (202)	E. faecalis	IC50, 20 μg/mL	[100]
					S. aureus and Aeromonas hydrophila	20 μg/mL
84	Aspergillus terreus	roots of Carthamus lanatus	Al-Azhar University campus in Cairo, Egypt	(22E,24R)-Stigmasta-5,7,22-trien-3-β-ol (203)	MRSA	IC50, 2.29 µM	[101]
85	Aspergillus flavus	Cephalotaxus fortunei	Taibai Mountains, Shaanxi Province, China	5-Hydroxymethylfuran-3-carboxylic acid (204), 5-acetoxymethylfuran-3-carboxylic acid (205)	S. aureus	MIC, 31.3 and 15.6 μg/mL	[102]
86	Aspergillus allahabadii BCC45335	root of Cinnamomum subavenium	Khao Yai National Park, Nakhon Ratchasima Province, Thailand	Allahabadolactone B (206), (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (207)	B. cereus	IC50, 12.50 and 3.13 µg/mL.	[103]
87	Aspergillus tubingensis	Lycium ruthenicum		6-Isovaleryl-4-methoxypyran-2-one (208), asperpyrone A (210), campyrone A (211)	E. coli, Pseudomonas aeruginosa, Streptococcus lactis and S. aureus	MIC values ranging from 62.5 to 500 μg/mL	[104]
				Rubrofusarin B (209)	E. coli	MIC, 1.95 μg/mL
88	Aspergillus tamarii FR02	roots of Ficus carica	Qinling Mountain in China’s Shaanxi province	Malformin E (212)	B. subtilis, S. aureus, P. aeruginosa, and E. coli	MIC, 0.91, 0.45, 1.82, and 0.91 μM	[105]
89	Aspergillus terreus	Roots of Carthamus lanatus	Al-Azhar University campus, Egypt	(22E,24R)-Stigmasta-5,7,22-trien-3-β-ol (203)	MRSA	IC50, 0.96μg/mL	[106]
				Aspernolide F (213)		IC50 6.39μg/mL
90	Aspergillus sp. (SbD5)	Leaves of Andrographis paniculata	Indralaya, Ogan Ilir, South Sumatra.	1-(3,8-Dihydroxy-4,6,6-trimethyl-6H-benzochromen-2-yloxy)propane-2-one (214), 5-hydroxy-4-(hydroxymethyl)-2H-pyran-2-one (215), (5-hydroxy-2-oxo-2H-pyran-4-yl)methyl acetate (216)	S. aureus, E. coli, S. dysenteriae and Salmonella typhi	Zone of inhibition diameters ranging from 8.1 to 12.1 mm at a concentration 500 μg/mL.	[107]
91	Aspergillus sp. IFB-YXS	Ginkgo biloba		Xanthoascin (217)	X. oryzae pv. oryzicola, Swings, E.amylovora, P. syringae pv. Lachrymans and C. michiganense subsp. sepedonicus	MICs, 20, 10, 5.0 and 0.31 µg/mL	[108]
				Prenylterphenyllin B (218)	X. oryzae pv.oryzicola Swings, E.amylovora, P. syringae pv. Lachrymans,	MICs of 20 µg/mL each
				Prenylcandidusin (219)	X. oryzae pv.oryzae Swings X. oryzae pv. oryzicola Swings	MIC values of 10 and 20 µg/mL
	Penicillium
92	Penicillium ochrochloron SWUKD4.1850	Kadsura angustifolia		4-O-Desmethylaigialomycin B (220), penochrochlactones C (221) and D (222)	Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa	MIC values between 9.7 and 32.0 μg/mL	[109]
93	Penicillium brefeldianum	Syzygium zeylanicum		p-Hydroxybenzaldehyde (223),	S. typhi, E. coli, and B. subtilis	MIC values of 64 g/mL	[110]
94	Penicillium vulpinum GDGJ-91	Sophorae tonkinensis	Baise, Guangxi Province, China	10-Demethylated andrastone A (224), andrastin A (227)	Bacillus megaterium	MIC value of 6.25 μg/mL	[111]
				Citreohybridone E (225), citreohybridonol (226), citreohybridone B (228)	B. megaterium	MIC values of 25, 12.5 and 25 μg/mL
				Citreohybridonol (226)	B. paratyphosus B, E. coli and S. aureus	MIC, 6.25, 25 and 25 μg/mL
				10-Demethylated andrastone A (224), citreohybridone E (225), andrastin A (227), andrastin B (228)	B. paratyphosus B	MIC, 12.5 or 25 μg/mL.
95	Penicillium nothofagi P-6,	Abies beshanzuensis	Baishanzu Mountain in Lishui, Zhejiang Province of China	Chromenopyridin A (229), viridicatol (230)	S. aureus ATCC29213	MIC, 62.5 and 15.6 μg/mL	[112]
96	Penicillium restrictum (strain G85)	Silybum marianum	Horizon Herbs, LLC (Williams, OR, USA).	ω-Hydroxyemodin (231)	Clinical isolates of MRSA	Quorum-sensing inhibition in both in vitro and in vivo models	[113]
97	Penicillium vulpinum	S. tonkinensis	Baise, Guangxi Province, China	(−)-3-Carboxypropyl-7-hydroxyphthalimide (232)	Shigella dysenteriae and Enterobacter areogenes	MIC, 12.5 μg/mL each	[114]
					B. subtilis	MIC, 25 μg/mL
					B. megaterium and Micrococcus lysodeikticus	MIC, 50 μg/mL
				(−)-3-Carboxypropyl-7-hydroxyphthalide methyl ester (233)	E. areogenes	MIC, 12.5 μg/mL
					B. subtilis, B. megaterium and M. lysodeikticus	MIC, 100 μg/mL.
98	Penicillium sumatrense GZWMJZ-313	Leaf of Garcinia multiflora	Libo, Guizhou Province of China	Citridone E (234), (–)-dehydrocurvularin (235)	S. aureus, P. aeruginosa, Clostridium perfringens, and E. coli	MIC values ranging from 32 to 64 μg/mL	[115]
99	Penicillium ochrochloronthe	Roots of Taxus media	Qingfeng Mountain, Chongqing, China	3,4,6-Trisubstituted α-pyrone derivatives, namely 6-(2′R-hydroxy-3′E,5′E-diene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (236), 6-(2′S-hydroxy-5′E-ene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran2-one (237), 6-(2′S-hydroxy-1′-heptyl)-4 -hydroxy-3-methyl-2H-pyran-2-one (238), trichodermic acid (239)	B. subtilis, Micrococcus luteus, S. aureus, B. megaterium, Salmonella enterica, Proteusbacillm vulgaris, Salmonella typhi, P. aeruginosa, E. coli and Enterobacter aerogenes	MIC values ranging from 25 to 50 μg/mL	[116]
100	Penicillium janthinellum SYPF 7899	Panax notoginseng	Wenshan region, Yunnan province, China	Brasiliamide J-a (240), brasiliamide J-b (241)	B. subtilis and S. aureus	MIC, 15 and 18 μg/mL,	[117]
				Peniciolidone (242), austin (243)	B. subtilis	MIC, 35 and 50 μg/mL
					S. aureus	MIC 39, and 60 μg/mL
101	Penicillium cataractum SYPF 7131	Ginkgo biloba		Penicimenolidyu A (244), penicimenolidyu B (245) and rasfonin (246)	S. aureus	MIC 65, 59 and 10 μg/mL	[118]
102	Penicillium sp.,	Tubers of Pinellia ternata	suburb of Nanjing, Jiangsu, China.	3′-Methoxycitreovirone (247), citreovirone (249)	E. coli and S. aureus	MIC = 62.6 and 76.6 μg/mL	[119]
				Helvolic acid (100)	S. aureus, P. aeruginosa, B. subtilis and E. coli	MIC = 5.8, 4.6, 42.2 and 75.0 μg/mL
				cis-bis-(Methylthio)-silvatin (248), trypacidin A (250)	S. aureus	MIC values of 43.4 and 76.0 μg/mL
				Trypacidin A (250)	B. subtilis	MIC = 54.1 μg/mL
103	Penicillium sp. R22	Nerium indicum	Qinling Mountain, Shaanxi Province, China	Viridicatol (251)	S. aureus	MIC value of 15.6 μg/mL	[120]
104	Penicillium sp. (NO. 24)	Tapiscia sinensis	Shennongjia National Forest Park China	Penicitroamide (252)	Erwinia carotovora subsp. Carotovora	MIC50 at 45 μg/mL	[121]
105	Penicillium sp. CAM64	Leaves of Garcinia nobilis	Mount Etinde, Southwest region Cameroon	Penialidin A (253)	Vibrio cholerae SG24 (1), V. cholerae CO6, V. cholerae NB2, V. cholerae PC2, S. flexneri SDINT,	MIC, 8–32 μg/mL	[122]
				Penialidin B (254)		MIC, 4–32 μg/mL
				Penialidin C (255)		MIC, 0.50, 16, 8, 0.50 and 8 μg/mL
				Citromycetin (256), brefelfin A (258)		MIC, 64–128 μg/mL
				p-Hydroxyphenylglyoxalaldoxime (257)		MIC, 32–64 μg/mL
106	Purpureocillium lilacinum	roots of Rauvolfia macrophylla	Mount Kalla in the Center Region of Cameroon	Purpureone (259)	B. cereus, L. monocytogenes, E. coli ATCC 8739, K. pneumoniae ATCC 1296, P. stuartii ATCC 29916, P. aeruginosa ATCC PA01	Zone of inhibition of 10.6, 12.3, 13.0, 8.7, 12.3, and 10.0, mm against (10 μL/6 mm Filter paper disks).	[123]
	Fusarium
	Neocosmospora sp. MFLUCC 17-0253	Rhizophora apiculate.		Mixture of 2-methoxy-6-methyl-7-acetonyl-8-hydroxy-1,4-naphthalenedione (260), and 5,8-dihydroxy-7-acetonyl-1,4-naphthalenedione (261)	Acidovorax citrulli	MIC value of 0.0075 mg/mL	[124]
				Anhydrojavanicin (262)		0.004 mg/mL
				Fusarnaphthoquinone (263)		0.025 mg/mL
107	Fusarium sp.	Mentha longifolia	Al Madinah Al Munawwarah, Saudi Arabia.	Fusaribenzamide A (264)	S. aureus and E. coli	MICs, 62.8 and 56.4 μg/disc	[125]
108	F. proliferatum AF-04	Green Chinese onion		5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	B. megaterium	MICs 25 μg/mL each.	[126]
				5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272)	B. subtilis	MICs, 50 μg/mL each.
				Indol-3-acetic acid (265), beauvericin (267), epicyclonerodiol oxide (269)	B. megaterium	MICs 50 μg/mL each
				Cyclonerodiol (268)	B. megaterium	MIC 12.50 μg/mL.
				epi-Cyclonerodiol oxide (269), methyl ether fusarubin (272)	E. coli	MIC 50 μg/mL
				5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), anhydrojavanicin (273)	E. coli	MIC 25 μg/mL
				epi-Cyclonerodiol oxide (269), 1,4-naphthoquinones, 5-O-methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272)	Clostridium perfringens	MICs 50, 50, 12.5 and 50 μg/mL
				Beauvericin (267), fusaproliferin (106), 5-O-methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	MRSA	MIC value of 50, 50, 12.5, 12.5, 12.5, and 25 μg/mL respectively.
				5-O-Methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	RN4220	MIC value of 50 μg/mL each.
				Methyl ether fusarubin (272), anhydrojavanicin (273)	NewmanWT	MIC value of 50 μg/mL each.
				Bassiatin (266)	NewmanWT	MIC, 50 μg/mL
109	Fusarium sp. TP-G1	Dendrobium officinable	Chongqing Academy of Chinese Materia Medica in China	Trichosetin (274), beauvericin (267), beauvericin A (275), enniatin H (277), enniatin I (278), enniatin MK1688 (279)	S. aureus and MRSA	IC50 values in the range of 2–32 μg/mL	[127]
				Enniatin B (276)	S. aureus and MRSA	IC50, 128 μg/mL each
				Fusaric acid (280), dehydrofusaric acid (281)	Acinetobacter baumannii	MIC, 64 and 128 μg/mL
	Fusarium sp. YD-2	Santalum album	Dongguan, Guangdong Province, China	Fusariumin A (282)	S. aureus and P. aeruginosa	MIC, 6.3 μg/mL	[128]
				Asperterpenoid A (283)	Salmonella enteritidis and Micrococcus luteus	MIC, 25.2 and 6.3 μg/mL
				Agathic acid (284)	B. cereus and M. luteus	MIC, 12.5 and 25.4 μg/mL
110	Fusarium chlamydosporium	Leaves of Anvillea garcinii	Al-Azhar University campus, Egypt	Fusarithioamide B (285)	E. coli, B. cereus, and S. aureus	MIC value of 3.7, 2.5 and 3.1 µg/mL	[129]
111	Fusarium solani A2	Glycyrrhiza glabra	Kashmir Himalayas of Jammu and Kashmir State, India	3,6,9-Trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]-isochromene-5,10-dione (286), fusarubin (287), 3-O-methylfusarubin (288), javanicin (289)	S. aureus (MTCC 96), K. pneumonia (MTCC 109), S. pyogenes (MTCC 442), B. subtilis (MTCC 121), B. cereus (IIIM 25), Micrococcus luteus (MTCC 2470) and E. coli (MTCC 730)	MIC values in the range of <1 to 256 μg/mL.	[130]
				Fusarubin (287)	Mycobacterium tuberculosis strain H37Rv	MIC, 8 μg/mL,
				3,6,9-Trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]-isochromene-5,10-dione (286), 3-O-methylfusarubin (288), javanicin (289)		MIC values of 256, 64, 32 μg/mL
112	Fusarium chlamydosporium	Anvillea garcinii	Al-Azhar University, Saudi Arabia	Fusarithioamide A (290)	B. cereus, S. aureus, and E. coli	MICs values of 3.1, 4.4, and 6.9 μg/mL	[131]
113	Fusarium sp.	Rhoeo spathacea	Pondok Cabe, Banten, Indonesia.	Javanicin (289)	M. tuberculosis and M. phlei	MIC 25 and 50 μg/mL	[132]
114	Fusarium sp.	Ficus carica	Qinling Mountain, Shaanxi Province, China	Helvolic acid Me ester (291)	B. subtilis, S. aureus, E. coli and P. aeruginosa	MIC, 6.25, 12.5, 6.25, and 3.13 μg/mL	[133]
				Helvolic acid (100)		MICs 6.25, 6.25, 6.25, and 3.13 μg/mL
				hydrohelvolic acid (292)		MICs 6.25, 12.5, 6.25, and 3.13 μg/mL
115	Fusarium sp.	-	-	Colletorin B (293), 4,5-dihydroascochlorin (294)	B. megaterium	5 and 10 mm zone of inhibition at 10 μg/mL concentration of	[134]
116	Fusarium sp.	Opuntia dillenii	South-Eastern arid zone of Sri Lanka	Equisetin (295)	B. subtilis	MIC, 8 μg/mL	[135]
					S. aureus and MRSA.	MIC, 16 μg/mL
117	Trichoderma harzianum	Zingiber officinale	Banyumas, Central Java, Indonesia	Pretrichodermamide A (296)	M. tuberculosis	MIC, 25 μg/mL (50 μM)	[136]
118	Trichoderma koningiopsis YIM PH30002	Panax notoginseng		Koninginin W (297), koninginin D (298), 7-O- and koninginin A (301)	B. subtilis	MIC of 128 μg/mL.	[137]
				Koninginin W (297), 7-O-methylkoninginin D (299)	S. typhimurium	MIC, 64 and 128 μg/mL;
				Koninginin W (297), koninginin (300)	E. coli	MIC of 128 μg/mL.
119	Trichoderma virens QA-8	Artemisia argyi		Trichocarotins I–M (302–306), CAF-603 (307), 7β-hydroxy CAF-603 (308), trichocarotins E–H (309–312), and trichocarane A (313)	E. coli EMBLC-1,	MIC values ranging from 0.5 to 32 µg/mL MIC = 0.5 µg/mL	[138]
				7β-Hydroxy CAF-603 (308)	Micrococcus luteus QDIO-3
120	Trichoderma koningiopsis QA-3	Artemisia argyi.		Trichodermaketone E (314), trichopyranone A (316), 3-hydroxyharziandione (317) and 10,11-dihydro-11-hydroxycyclonerodiol (318), harziandione (321)	E. coli	MIC values ranging from 0.5 to 64 μg/mL	[139]
				Trichopyranone A (316), 3-hydroxyharziandione (317), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	M. luteus	MIC values ranging from 1 to 16 μg/mL
				Trichodermaketone E (314), 4-epi-7-O-methylkoninginin D (315), 3-hydroxyharziandione (317), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	P. aeruginosa	with MIC values ranging from 4 to 16 μg/mL
				Trichodermaketone E (314), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	V. parahaemolyticus	MIC values ranging from 4 to 16 μg/mL.
				3-Hydroxyharziandione (317)	E. coli	MIC value of 0.5 µg/mL
				6-(3-Hydroxypent-1-en-1-yl)-2H-pyran-2-one (320)	M. luteus	MIC value of 1 µg/mL
121	Trichoderma koningiopsis QA-3	Artemisia argyi	Qichun of the Hubei Province, China	15-Hydroxy-1,4,5,6-tetra-epi-koninginin G (322)	Vibrio alginolyticus	MIC, 1 μg/mL	[140]
				Koninginin U (323), 14-ketokoninginin B (324)	Vibrio harveyi and Edwardsiella tarda	MICs 4 and 2 µg/mL
122	Trichoderma atroviride B7	Colquhounia coccinea var. mollis	Kunming Botanical Garden, Yunnan, China	Harzianol I (325)	S. aureus, B. subtilis, and M. luteus	EC50 7.7, 7.7, and 9.9 μg/mL	[141]
123	Trichoderma longibrachiatum MD33	Dendrobium nobile	Jinshishi, Chishui, China	Dendrobine (326)	Bacillus mycoides, B. subtilis, and Staphylococcus	Zone of inhibition of 9, 12 and 8 mm	[142]
124	Trichoderma virens QA-8,	Artemisia argyi	Qichun of Hubei Province in central China	Trichocadinins B-D and G (327–330)	E. coli EMBLC-1, Aeromonas hydrophilia QDIO-1, Edwardsiella tarda QDIO-2, E. ictarda QDIO-10, Micrococcus luteus QDIO-3, P. aeruginosa QDIO-4, Vibrio alginolyticus QDIO-5, V. anguillarum QDIO-6, V. harveyi QDIO-7, V. parahemolyticus QDIO-8, and V. vulnificus QDIO-9	MIC in the range of 8–64 μg/mL	[143]
				Trichocadinin G (330)	Ed. tarda and V. anguillarum	MIC values of 1 and 2 μg/mL
125	Trichoderma koningiopsis A729	Morinda officinalis		Koninginols A-B (331–332)	B. subtilis	MIC values of 10 and 2 μg/mL	[144]
126	Trichoderma koningiopsis QA-3	Artemisia argyi	Qichun	Ent-koninginin A (333)	V. vulnificus	MIC, 4 μg/mL	[145]
				Ent-koninginin A (333), trichoketide A (339)	E. coli, E. tarda, V. anguillarum, and V. parahemolyticus	MICs ranging from 8 to 64 μg/mL
				Ent-koninginin A (333), 1,6-di-epi-koninginin A (334), 15-hydroxykoninginin A (335), 10-deacetylkoningiopisin D (336), koninginin T (337), koninginin L (338), trichoketide A (339)	E. coli	MIC, 64 μg/mL each
					E. tarda, V. alginolyticus, and V. anguillarum	MIC values ranging from 4 to 64 μg/mL
	Alternaria
127	Alternaria alternata ZHJG5	Cercis chinensis		Isotalaroflavone (340), 4-hydroxyalternariol-9-methyl ether (341), verrulactone A (342)	Xanthomonas oryzae pv. Oryzae, Xanthomonas oryzae pv. oryzicola and Ralstonia solanacearum (Rs)	MIC ranging from 0.5 to 64 μg/mL.	[146]
128	Alternaria sp. PfuH1	Pogostemon cablin (Pacholi).		Alternariol (44), altertoxin VII (343), altenuisol (344)	S. agalactiae	MIC, 9.3, 17.3 and 85.3 μg/mL	[147]
				Altenuisol (344)	E. coli	MIC, 128 μg/mL
129	Alternaria alternata ZHJG5	Cercis chinensis		Alternariol (44), altenuisol (344), alterlactone (345), Dehydroaltenusin (346)	FabH of Xanthomonas oryzae pv. oryzae (Xoo)	IC50 values from 29.5 to 74.1 μM	[148]
					Xanthomonas oryzae pv. Oryzae	MIC values from 4 to 64 μg/mL.
				Alternariol (44), alterlactone (345)	Rice bacterial leaf blight	a protective efficiency of 66.2 and 82.5% at the concentration of 200 μg/mL
130	Alternaria alternata MGTMMP031	Vitex negundo	Madurai, Tamil Nadu, India	Alternariol Me ether (347)	B. cereus, Klebsiella pneumoniae	MIC, 30 µM/L	[149]
					E. coli, Salmonella typhi, Proteus mirabilis, S. aureus and S. epidermidis	MIC, 35 µM/L
131	Alternaria alternata	Grewia asiatica		3,7-Dihydroxy-9-methoxy-2-methyl-6H-benzo[c]chromen-6-one (348)	S. aureus (ATCC 29213), VRE, and MRSA	MIC, 32, 32 and 8 μg/mL	[150]
				Alternariol (44)	S. aureus (ATCC 29213), VRE, and MRSA	MIC, 128, 128, and 64 μg/mL
132	Alternaria sp. Samif01	Salvia miltiorrhiza	Beijing Medicinal Plant Garden, Beijing, China	Altenuisol (344), 4-hydroxyalternariol-9-methyl ether (349) and alternariol (44)	A. tumefaciens, B. subtilis, Pseudomonas lachrymans, Ralstonia solanacearum, Staphylococcus hemolyticus and Xanthomonas vesicatorya	MIC values in the range of 86.7–364.7 μM	[151]
133	Alternaria sp. Samif01	Salvia miltiorrhiza	Beijing, China	Alternariol 9-Me ether (347)	Bacillus subtilis ATCC 11562 and Staphylococcus haemolyticus ATCC 29970, A. tumefaciens ATCC 11158, Pseudomonas lachrymans ATCC 11921, Ralstonia solanacearum ATCC 11696, and Xanthomonas vesicatoria ATCC 11633	IC50 values varying from 16.00 to 38.27 g/mL	[152]
134	Alternaria sp. and Pyrenochaeta sp.,	Hydrastis canadensis	William Burch in Hendersonville, North Carolina	Altersetin (350), macrosphelide A (351)	S. aureus	MIC, 0.23, and 75 μg/mL	[153]
135	Simplicillium lanosoniveum	Hevea brasiliensis	Songkhla Province, Thailand	Simplicildones K (352)	S. aureus ATCC25923, MRSA	MIC, 128μg/mL	[154]
				Botryorhodine C (353), simplicildones A (354)	S. aureus ATCC25923, MRSA	MIC, 32 μg/mL each
136	Simplicillium sp. PSU-H41	Hevea brasiliensis	Songkhla Province, Thailand	Botryorhodine C (353), simplicildone A (354)	S. aureus	MIC, 32 μg/mL each	[155]
				Botryorhodine C (353)	MRSA	MIC, 32 μg/mL
	Cladosporium
137	Cladosporium cladosporioides	Zygophyllum mandavillei	Al-Ahsa, Saudi Arabia	Isocladosporin (355), 5′- hydroxyasperentin (356), 1-acetyl-17-methoxyaspidospermidin-20-ol (357), and 3-phenylpropionic acid (358)	Xanthomonas oryzae and Pseudomonas syringae	MIC values in the range of 7.81 to 125 µg/mL	[156]
138	Cladosporium sphaerospermum WBS017	Fritillaria unibracteata var. wabuensis	Western Sichuan Plateau of China	Cladosin L (359)	S. aureus ATCC 29213 and S. aureus ATCC 700699	MICs, 50 and 25 mM,	[157]
139	Cladosporium sp.	Rauwolfia serpentina		Me ether of fusarubin (360)	S. aureus, E. coli, P. aeruginosa and B. megaterium	Zone of inhibition of 27, 25, 24 and 22 mm (40μg/disk)	[158]
	Pestalotiopsis
140	Pestalotiopsis sp. M-23	Leucosceptrum canum	Kunming Botanical Garden, China	11-Dehydro-3a-hydroxyisodrimeninol (361)	B. subtilis	IC50, 280.27 µM	[159]
141	Pestalotiopsis sp.	Melaleuca quinquenervia	Toohey Forest, Queensland, Australia	(1S,3R)-austrocortirubin (362), (1S,3S)-austrocortirubin (363), 1-deoxyaustrocortirubin (364)	Gram-pos.	100 μM	[160]
142	Neopestalotiopsis sp.			Neopestalotins B (365)	B. subtilis, S. aureus, S. pneumoniae	MIC, 10, 20, and 20 μg/mL	[161]
	Phoma
143	Phoma cucurbitacearum	Glycyrrhiza glabra	Jammu (J&K).	Thiodiketopiperazine derivatives (366) and (367)	S. aureus and Streptococcus pyogenes	IC50, 10 μM	[162]
144	Phoma sp. JS752	Phragmites communis	Seochun, South Korea	Barceloneic acid C (368)	Listeria monocytogenes and Staphylococcus pseudintermedius	MIC, 1.02 μg/mL each	[163]
145	Setophoma sp.,	Psidium guajava fruits		Thielavins T (369), U (370) and V (371)	S. aureus ATCC 25923	MIC, 6.25, 50, and 25 μg/mL	[164]
	Colletotrichum
146	Colletotrichum gloeosporioides B12	Illigera rhodantha	Qionghai City, Hainan Province, China	Colletolides A (372) and B (373), and 3-methyleneisoindolinon (374)	Xanthomonas oryzae pv. oryzae,	MIC, 128 μg/mL each	[165]
				Sclerone (375)	X. oryzae pv. oryzae	MIC, 64 μg/mL
147	Colletotrichum sp. BS4	Buxus sinica	Guangzhou, Guangdong Province, China	Colletotrichones A (376)	E. coli and B. subtilis	MIC, 1.0 and 0.1 μg/mL	[166]
				Colletotrichone B (377)	S. aureus (DSM 799)	MIC, 5.0 μg/mL
				Colletotrichone C (378)	E. coli	MIC, 5.0 μg/mL
	Minor Taxa of Anamorphic Ascomycetes
148	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	Agricultural University Beijing China	Rhizopycnolide A (379)	A. tumefaciens, B. subtilis, and P. lachrymans	MICs 100, 75, and 100 μg/mL	[167]
				Rhizopycnin C (380), penicilliumolide D (384), alternariol (44)	A. tumefaciens, B. subtilis, Pseudomonas lachrymans, Ralstonia solanacearum, Staphylococcus hemolyticus, and Xanthomonas vesicatoria,	MICs in the range 25–100 μg/mL
				Rhizopycnin D (381)	A. tumefaciens, B. subtilis, and R. solanacearum,	MIC 50 μg/mL each,
					X. vesicatoria	MIC, 75 μg/mL.
				Palmariol B (383), Alternariol 9-methyl ether (347)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, and X. vesicatoria,	IC50 values in the range 16.7−34.3 μg/mL
				TMC-264 (382)	B. subtilis	MIC 50 μg/mL
149	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	China Agricultural University, Beijing	Rhizoperemophilane K (385), 1α-hydroxyhydroisofukinon (386), 2-oxo-3-hydroxyeremophila-1(10),3,7(11), 8-tetraen-8,12-olide (387)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. haemolyticus, and X. vesicatoria,	MIC, 32~128 μg/mL	[168]
150	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	China Agricultural University (CAU), Beijing 100101, China	Rhizopycnis acid A (388)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. hemolyticus and X. vesicatoria	MICs, 20.82, 16.11, 23.48, 29.46, 21.11, and 24.31 µg/mL	[169]
				Rhizopycnis acid B (389)		MICs, 70.89, 81.28, 21.23, 43.40, 67.61, and 34.86 µg/mL
151	Leptosphaeria sp. XL026	Panax notoginseng	Shijiazhuang, Hebei province, China	Leptosphin B (390), conidiogenone C (391), conidiogenone D (392), conidiogenone G (393)	B. cereus	MICs 12.5–6.25 μg/mL	[170]
				Conidiogenone D (392)	P. aeruginosa	MIC, 12.5 μg/mL
152	Lophiostoma sp. Eef-7	Eucalyptus exserta.		Scorpinone (394), 5-deoxybostrycoidin (395)	Ralstonia solanacearum	Zone of inhibition of 9.86 and 9.58 mm at 64 µg concentration	[171]
	Lophiostoma sp. Sigrf10	Siraitia grosvenorii	Guangxi Province of China	(8R,9S)-dihydroisoflavipucine (396), (8S,9S)-dihydroisoflavipucine (397)	B. subtilis, A. tumefaciens, Ralstonia solanacearum, and Xanthomonas vesicatoria	IC50 in the range of 35.68–44.85 µM	[172]
153	Cytospora chrysosperma	Hippophae rhamnoides		Cytochrysin A (398)	Enterococcus faecium	MIC, 25 μg/mL	[173]
				Cytochrysin C (399)	MRSA	MIC, 25 μg/mL
154	Microsphaeropsis sp. Seimatosporium sp.	Salsola oppositifolia	Gomera, Spain	Microsphaerol (400)	B. megaterium and E. coli,	Zone of inhibition 8 and 9 mm at 0.05 mg concentration	[174]
				Seimatorone (401)	B. megaterium and E. coli,	Zone of inhibition 3 and 7 (partial) mm at a 0.05 mg concentration
155	Epicoccum nigrum MK214079	Salix sp.	Caucasus mountains Lago-Naki, Russia	Epicocconigrone A (402), epipyrone A (403), and epicoccolide B (404)	S. aureus ATCC 29213	MIC values ranging from 25 to 50 μM	[175]
156	Epicoccum nigrum	Entada abyssinica	Balatchi (Mbouda), in the West region of Cameroon	p-Hydroxybenzaldehyde (223)	S. aureus, B. cereus, P. aeruginosa, and E. coli	MICs 50, 25, 50, and 25 µg/mL	[176]
				Beauvericin (267)	S. aureus, B. cereus, and Salmonella typhimurium	MICs 3.12, 12.5, and 12.5 µg/mL
				Indole-3-carboxylic acid (405)	S. aureus and E. faecalis	MIC values of 6.25 and 50 µg/mL
				Quinizarin (406)	S. aureus, B. cereus St	MIC values of 50 µg/mL each
157	Stemphylium lycopersici	S. tonkinensis		Xylapeptide B (407)	B. subtilis, S. aureus and E. coli	MIC, 12.5, 25 and 25 μg/mL	[177]
				Cytochalasin E (408)	B. subtilis, S. aureus, B. anthracis, S. dysenteriae, and E. coli	MIC 12.5 to 25 μg/mL
				6-Heptanoyl-4-methoxy-2H-pyran2-one (409)	S. paratyphi B	MIC, 12.5 μg/mL
				(–)-5-Carboxymellein (410)	B. subtilis, S. aureus, B. anthracis, S. dysenteriae, S. paratyphi, E. coli and S. paratyphi B	MIC values from 12.5 to 25 μg/mL
158	Stemphylium globuliferum,	Juncus acutus	Egypt	Dihydroaltersolanol C (411)	S. aureus	MICs of 49.7 μM	[178]
159	Lecanicillium sp. (BSNB-SG3.7 Strain)	Sandwithia guyanensis	St Elie, France.	Stephensiolides I (412), D (413), G (414), stephensiolide F (415)	MRSA	MICs 4, 32, 16 and 32 μg/mL	[179]
160	Nigrospora sphaerica	Adiantum philippense	Western Ghats region near Virajpete, India	Phomalactone (416)	E. coli and X. campestris	MIC 3.12 μg/mL	[180]
					S. typhi, B. subtilis, B. cereus, and K. pneumonia	MIC value of 6.25 μg/mL
					S. aureus, S. epidermidis, and C. albicans	MIC of 12.5 μg/mL
161	Nigrospora sp. BCC 47789	Choerospondias axillaris	Khao Yai National Park, Nakhon Ratchasima Province, Thailand	Nigrosporone B (417)	M. tuberculosis, B. cereus and E. faecium	MICs 172.25, 21.53 and 10.78 μM	[181]
162	Curvularia sorghina BRIP 15900)	Rauwolfia macrophylla	Mount Kalla in Cameroon	2′-Deoxyribolactone (419), hexylitaconic acid (419)	E. coli, Micrococcus luteus, Pseudomonas agarici and Staphylococcus warneri	MIC ranging between 0.17 μg/mL and 0.58 μg/mL	[182]
163	Curvularia lunata	Paepalanthus chiquitensis	Serra do Cipó, in Minas Gerais State, Brazil	Triticones E (420), F (421)	E. coli,	MIC 62.5 μg/mL	[183]
164	Bipolaris sp. L1-2	Lycium barbarum	Ningxia Province, China	Cochlioquinones B (422), C (423), isocochlioquinones (424)	B. subtilis, C. perfringens, and P. viridiflava	MICs 26 μM	[184]
165	Bipolaris eleusines	Potatoes	nursery of Yunnan Agricultural University, Kunming, Yunnan China	(S)-5-Hydroxy-2-(1-hydroxyethyl)-7-methylchromone (425), 5,7-dihydroxyl-2,6,8-trimethylchromone (426)	Staphylococcus aureus subsp. Aureus	inhibition rates of 56.3 and 32 %, at the concentration of 128 μg/mL	[185]
166	Bionectria sp. Y1085,	Huperzia serrata	Xichou County, Yunnan Province, China	Bionectin D (427), bionectin E (428), verticillin A (430), sch 52901 (429), gliocladicillin C (431)	E. coli, S. aureus, and S. typhimurium ATCC 6539,	MIC values ranging from 6.25–25 µg/mL	[186]
167	Cylindrocarpon sp.,	Sapium ellipticum	Haut Plateaux region, Cameroon	Pyrrocidine A (432)	S. aureus, ATCC 25923, S. aueus ATCC 700699, S. aueus ATCC 700699, E. faecalis ATCC 29212, E. faecalis ATCC 51299, E. faecium ATCC 35667, E. faecium ATCC 700221	MIC values ranging from 0.78 to 25 μM	[187]
				19-O-Methylpyrrocidine B (433)	S. aureus ATCC25923 and ATCC700699	MIC, 50 and 25 μM,
168	Eupenicillium sp. LG41.9 treated with HDAC inhibitor, nicotinamide (15 mg/100 mL)	Xanthium sibiricum	Taian, Shandong Province, China	Eupenicinicol C (434)			[188]
				Eupenicinicol D (435),	S. aureus	MIC 0.1 μg/mL,
				Eujavanicol A (436)	E. coli	MIC 5.0 μg/mL
				Eupenicinicol A (437)
169	Dendrothyrium variisporum	Globularia alypum	Ain Touta, Batna 05000, Algeria	2-Phenylethyl 3-hydroxyanthranilate (438)	B. subtilis and M. luteus	MICs 8.33 and 16.66 μg/mL	[189]
				2-Phenylethyl anthranilate (439)	B. subtilis and M. luteus	66.67 μg/mL each
170	Exserohilum rostratum	Phanera splendens (Kunth) Vaz		Ravenelin (440)	Bacillus subtilis and Staphylococcus aureus	MICs, 7.5 and 484 μM	[190]
171	Exserohilum rostratum	Bauhinia guianensis		Monocerin (441)	P. aeruginosa	MIC, 62.5 µg/mL	[191]
				Annularin I (442)	E. coli and B. subtilis	MIC, 62.50 and 31.25 µg/mL
				Annularin J (443)	E. coli and B. subtilis	MIC, 62.50 µg/mL each
	Basidiomycete
172	Psathyrella candolleana	Ginkgo biloba		Quercetin (444), carboxybenzene (445), and nicotinamide (446)	S. aureus	MIC 0.3906, 0.7812 and 6.25 μg/mL	[192]
173	Irpex lacteus DR10-1	Distylium chinense	Banan district of Chongqing in the TGR area, China	Irpexlacte A (447), irpexlacte B-D (448–450)	P. aeruginosa	MIC values ranging from 23.8 to 35.4 μM	[193]
	Zygomycetes
174	Mucor irregularis			Chlorflavonin (451)			[194]

Table 1. Anti-bacterial metabolites reported from endophytic fungi.

Sr. No.	Fungus	Source	Locality	Compounds Isolated	Biological Target	Biological Activity (MIC/IC50/ID50)	Reference
Ascomycetes
Diaporthe
1	Diaporthe sp.	Uncaria gambier		(+)-1,1′-Bislunatin (1) and (+)-2,2′- epicytoskyrin A (2)	Mycobacterium tuberculosis strains H37Rv	MICs 0.422 and 0.844 μM	[18]
2	Diaporthe sp. GDG-118	Sophora tonkinensis	Hechi City, China	21-Acetoxycytochalasin J3 (3)	Bacillus anthraci and E. coli	inhibited at 12.5 μg/mL concentration	[19]
3	Phomopsis fukushii.			1-(3-Hydroxy-1-(hydroxymethyl)-2-methoxy-6-methylnaphthalen-7-yl) propan-2-one (4) and 1-(3-hydroxy-1- (hydroxymethyl)-6-methylnaphthalen-7-yl)propan-2-one (5)	MRSA	Zone of inhibition of 10.2 and 11.3 mm (6 mm strile filterpaper disc were impregnated with 20µL (50 µg) of each compound)	[20]
4	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	3-Hydroxy-1-(1,8- dihydroxy- 3,6-dimethoxynaphthalen-2-yl)propan-1-one (6), 3-hydroxy-1-(1,3,8-trihydroxy-6-methoxynaphthalen-2-yl)propan-1-one (7) and 3-hydroxy-1-(1,8-dihydroxy3,5-dimethoxynaphthalen-2-yl) propan-1-one (8)	MRSA- ZR11	MIC, 8, 4, and 4 µg/mL,	[21]
5	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	1-[2-Methoxy-4-(3-methoxy-5-methylphenoxy)-6-methylphenyl]-ethanone (9) and 1-[4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6-methylphenyl]-ethanone (10)	MRSA	Zone of inhibition 13.8 and 14.6 mm	[22]
6	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, P. R. China	4-(3-Methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (11), 4-(3-Hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-methylphenol (12) and 4-(3-methoxy-5-methylphenoxy)-2-(3-hydroxypropyl) -6-methylphenol (13)	MRSA	Zone of inhibition of 20.2, 17.9 and 15.2 mm (tested at 50µg/6 mm disc)	[23]
7	Phomopsis fukushii	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China.	1-(4-(3-Methoxy-5-methylphenoxy)-2-methoxy-6-methylphenyl)-3-methylbut-3-en-2-one (14), 1-(4-(3-(hydroxymethyl)-5-methoxyphenoxy)-2-methoxy-6- methylphenyl)-3-methylbut-3-en-2-one (15), 1-(4-(3-hydroxy-5-(hydroxymethyl)phenoxy)-2-methoxy-6- methylphenyl)-3-methylbut-3-en-2-one (16)	MRSA	Zone of inhibition of 21.8, 16.8 and 15.6 mm, (50 µg/6 mm disc)	[24]
8	Phomopsis sp.	-	-	3-Hydroxy-6-hydroxymethyl-2,5-dimethylanthraquinone (17), 6-hydroxymethyl-3-methoxy-2,5-dimethylanthraquinone (18)	MRSA	IZD 14.2 and 14.8 mm	[25]
9	Diaporthe sp.	Pteroceltis tatarinowii	Mufu Mountain of Nanjing, China.	Diaporone A (19)	B. subtilis	MIC, 66.7 μM,	[26]
10	Phomopsis prunorum (F4-3).	-	-	(−)-1 and (+)- Phomoterpenes A and B (20) phomoisocoumarins C (21), D (22)	X. citri pv. phaseoli var. fuscans	MIC, 31.2, 62.4, 31.2, and 31.2 μg/mL,	[27]
					Pseudomonas syringae pv. Lachrymans	MIC, 31.2, 15.6, 31.2 and 15.6 μg/mL
11	Diporthe vochysiae LGMF1583	Vochysia divergens	-	Vochysiamides A (23)	KPC (Klebsiella pneumoniae carbapenemase producing).	MIC, 1.0 μg/mL	[28]
				Vochysiamides B (24)	KPC, MSSA, MRSA	MIC, 0.08, 1.0, and 1.0 µg/mL
12	Phomopsis asparagi	Paris polyphylla var. yunnanensis	Kunming, Yunnan, China	4-(3-Methoxy-5-methylphenoxy)-2-(2-hydroxyethyl)- 6-(hydroxymethyl)phenol (25), 4-(3-Hydroxy-5-methylphenoxy)-2-(2-hydroxyethyl)-6-(hydroxymethyl)phenol(26)	MRSA	Zone of inhibition of 10.8 and 11.4 mm	[29]
13	Phomopsis sp.	Paris polyphylla var. yunnanensis	ShiZhong, Yunnan, China	5-Methoxy-2-methyl-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (27), 2-(hydroxymethyl)-5-methoxy-7-(3-methyl-2-oxobut-3-enyl)-1-naphthaldehyde (28)	MRSA	Zone of inhibition of 14.5 and 15.2 mm	[30]
14	Diaporthe terebinthifolii LGMF907	Schinus terebinthifolius	Curitiba, Paraná, Brazil	Diaporthin (29)	E. coli, Micrococcus luteus, MRSA, and S. aureus	Zone of inhibition 1.73, 2.47, 9.50, and 9.0 mm tested at 100 μg/disk.	[31]
				Orthosporin (30)		Zone of inhibition of 1.03, 1.53C, 9.0, and 9.33 mm
15	Phomopsis/Diaporthe sp. GJJM 16	Vitex negundo	Azhiyar, Pollachi, Tamilnadu, India	(2Z)-2-(1,4-dihydro-2-hydroxy-1-((E)-2-mercapto-1 (methylimino)ethyl) pyrimidine-4-ylimino)-1-(4,5-dihydro-5-methylfuran-3-yl)-3-methylbutane-1-one (31)	S. aureus, and P. aeroginosa	MIC of 1.25 μg/mL against each organism	[32]
16	Phomopsis sp. PSU-H188	Hevea brasiliensis	Trang Province, Thailand.	Diaporthalasin (32)	S. aureus ATCC25923, MRSA	MIC, 4 μg/mL each	[33]
				Cytosporone B (33)		MIC, 32 and 16 μg/mL
				Cytosporone D (34)		MIC, 64 and 32 μg/mL
17	Diaporthe terebinthifolii GG3F6	Glycyrrhiza glabra	Jammu, J & K, India	Diapolic acid A (35), B (36) xylarolide (37) phomolide G (38)	Yersinia enterocolitica	IC50, 78.4, 73.4, 72.1 and 69.2 μM	[34]
18	Diaporthe sp. F2934	leaves of Siparuna gesnerioides	Chagres National Park, a protected area of Panama	Phomosine A (39)	S. aureus (ATCC 25923), Streptococcus oralis (ATTC 35037), Enterococcus faecalis (ATCC 19433), Enterococcus cloacae (ATCC 13047), Bordetella bronchiseptica (CECT 440),	Zone of Inhibition 12, 9, 10, 11, 10 and 10 mm at 4 µg/mL concentration	[35]
				Phomosine C (40)		Zone of Inhibition 9, 6, 8, 8, 8 and 9 mm at 4 µg/mL concentration
19	Phomopsis sp.,	Garcinia kola nuts	bought at Mokolo local market in Yaounde (Cameroon)	18-Methoxycytochalasin J (41), cytochalasins H (42) and J (43), alternariol (44)	Shigella flexneri	MIC, 128 μg/mL each	[36]
				18-Methoxycytochalasin J (41), cytochalasins H (42)	S. aureus ATCC 25923	MIC, 128 and 256 μg/mL
20	Diaporthe sp. LG23	Mahonia fortunei	Shanghai, China	19-nor-Lanosta-5(10),6,8,24-tetraene-1α,3β,12β,22S-tetraol (45)	S. aureus, E. coli, Bacillus subtilis, P. aeruginosa, Streptococcus pyogenes	MIC, 5.0, 5.0, 2.0, 2.0 and 0.1 µg/mL	[37]
				3β,5α,9α-Trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (46), and chaxine C (47)	B. subtilis	MIC, 5.0 µg/mL each
21	Diaporthales sp. E6927E	Ficus sphenophyllum	Ecuadorean dry forest near the Napo River, USA	Pyrrolocin A (48)	S. aureus and E. faecalis	MICs 4 and 5 µg/mL	[38]
	Xylaria
22	Xylaria ellisii	Blueberry (Vaccinium angustifolium)		Ellisiiamide (49)	Escherichia coli	MIC, 100 μg/mL	[39]
23	Xylaria sp. GDG-102	S. tonkinensis	Hechi, Guangxi province, China	Xylareremophil (50)	Micrococcus luteus and Proteus vulgaris	MIC 25 μg/mL each	[40]
				Mairetolides B (51)	M. luteus	MIC, 50 μg/mL
				Mairetolide G (52)	P. vulgaris M. luteus	MIC 25 and 50 μg/mL
				Xylareremophil (50), mairetolides B (51), and G (52)	Micrococcus lysodeikticus and Bacillus subtilis	MIC 100 μg/mL
24	Xylaria sp. (GDG-102)	Leaves of S. tonkinensis		6-Heptanoyl-4-methoxy-2H-pyran-2-one (53)	E. coli as well as S. aureus	MIC, 50 μg/mL	[41]
25	Xylaria sp. GDG-102	S. tonkinensis	Hechi, Guangxi province, China	Xylarphthalide A (54)	B. subtilis and E. coli,	MIC, 12.5 μg/mL each	[42]
					B. megaterium, S. aureus, S. dysenteriae and S. paratyphi	MIC, 25 μg/mL each
				(−)-5-Carboxymellein (55)	B. Subtilis	MIC, 12.5 μg/mL
					B. anthracis, B. megaterium, S. aureus, E. coli, S. dysenteriae and S. paratyphi B	MIC, 25 μg/mL
				(−)-5-Methylmellein (56)	B. subtilis and S. aureus	MIC, 12.5 μg/mL
					B. megaterium, E. coli and S. dysenteriae	25 μg/mL
26	Xylaria sp.,	Taxus mairei.		3,7-Dimethyl-9-(-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl) nona-1,6-dien-3-ol (57)	B. subtilis ATCC 9372, B. pumilus 7061 and S. aureus ATCC 25923	48.1, 31.6 and 47.1% inhibition.	[43]
				Nalgiovensin (58)	S. aureus ATCC 25923, B. subtilis ATCC 9372, B. pumilus ATCC 7061 and E. coli ATCC 25922	42.1, 36.8, 47.1 and 41.2% inhibition.
	Chaetomium
27	C. globosum 7s-1,	Rhapis cochinchinensis		Xanthoquinodin B9 (59), xanthoquinodin A1 (60), xanthoquinodin A3 (61)	B. cereus	MICs of 0.87, 0.44 and 0.22 μM,	[45]
				Xanthoquinodin B9 (59), xanthoquinodin A1 (60), xanthoquinodin A3 (61)	S. aureus and MRSA	MIC values ranging from 0.87 to 1.75 μM
				3-Epipolythiodioxopiperazines, chetomin (62), chaetocochin C (63) and dethio-tetra(methylthio)chetomin (64)	B. cereus ATCC 11778, S. aureus ATCC 6538, and MRSA	MIC values ranging from 0.02 pM to 10.81 μM.
				Chetomin (62)	B. cereus, S. aureus and MRSA	MICs, 0.35 μM, 10.74 and 0.02 pM
				Compounds 59–64	E. coli ATCC 25922, P. aeruginosa ATCC 27853, and Salmonella typhimurium ATCC 13311	MICs of 45.06 to >223.72 μM
				Epipolythiodioxopiperazines (62–64)	Mycobacterium tuberculosis	MICs, 0.55, 4.06 and 8.11 μM,
28	Chaetomium sp. SYP-F7950	Panax notoginseng	Wenshan, Yunnan, China	Chaetocochin C (63), chetomin A (65), and chetomin (62)	S. aureus, B. subtilis, Enterococcus faecium	MIC values ranging from 0.12 to 19.3 μg/mL	[46]
29	Chaetomium sp. HQ-1,	Astragalus chinensis	Tai’an, Shandong Province, China	Differanisole A (66)	L. monocytogenes S. aureus and MRSA,	MIC, 16, 128, 128 μg/mL	[47]
				2,6-Dichloro-4-propylphenol (67), 4,5-dimethylresorcinol (68)	L. monocytogenes	MICs of 64 and 32 μg/mL,
30	Chaetomium nigricolor F5,	Mahonia fortune	Qingdao, People’s Republic of China	Chamiside A (69)	S. aureus	MIC of 25 μg/mL	[48]
31	C. globosum	Salvia miltiorrhiza	Shenyang, Liaoning province, China	Equisetin (70)	Multidrug-resistant E. faecalis, E. faecium, S. aureus, and S. epidermidis	MIC values of 3.13, 6.25, 3.13, and 6.25 μg/mL	[49]
32	Chaetomium sp. Eef-10,	Eucalyptus exserta	Guangdong Province, China	Mollicellins H (71)	S. aureus ATCC29213, S. aureus N50, MRSA,	IC50, 5.14, and 6.21 μg/mL	[50]
				Mollicellin O (72)	S. aureus ATCC29213 and S. aureus N50	IC50, 79.44 and 76.35 μg/mL
				Mollicellin I (73)		IC50, 70.14 and 63.15 μg/mL
33	Chaetomium sp. M336	Huperzia serrata	Xichou County, Yunnan Province, China	6-Formamidochetomin (74)	E. coli, S. aureus, S. typhimurium ATCC 6539 and E. faecalis	MIC, 0.78 μg/mL	[51]
34	Chaetomium globosum	Nymphaea nouchali	Udugampola in the Gampaha District, Sri Lanka	Chaetoglobosin A (75)	B. subtilis, S. aureus, and MRSA	MIC, 16, 32 and 32 μg/mL	[52]
				Chaetoglobosin B (76)		>64 μg/mL
	Talaromyces
35	Talaromyces pinophilus XL-1193	Salvia miltiorrhiza	Shenyang, Liaoning province, China	Pinophol A (77)	Bacterium paratyphosum B	MIC, 50μg/mL	[53]
36	Talaromyces purpureogenus XL-25	Panax notoginseng	Shijiazhuang, Hebei Province, China	Talaroconvolutin A (78)	B. subtilis Micrococcus lysodeikticus, Vibrio parahaemolyticus	MIC value of 1.56 μM	[54]
				Talaroconvolutin B (79)		MIC = 0.73 and 0.18 μM
37	Talaromyces purpureogenus	Panax notoginseng		(1S,5S,7S,10S)-dihydroxyconfertifolin (80)	E. coli	MIC, 25 μM	[55]
38	Talaromyces funiculosus -Salicorn 58.			Talafun (81)	E. coli, S. aureus	MIC, 18 and 93 μM	[56]
				N-(2′-hydroxy-3′-octadecenoyl)-9-methyl-4,8-sphingadienin (82)	Mycobacterium smegmatis, S. aureus, Micrococcus tetragenus, and E. coli	MIC, 85, 90, 24, and 68, 93 μM
				Chrodrimanin A (83)	S. aureus, M. tetragenus, Mycobacterium phlei, and E. coli	MIC, 67, 28, 47, and 26 μM
				Chrodrimanin B (84)	E.coli	MIC, 43 μM.
39	Talaromyces sp. LGT-2	Tripterygium wilfordii.		Alkaloids 85–90	E. coli, P. aeruginosa, S. aureus, Bnfillus licheniformis, and Streptococcus pneumoniae	MICs in the range of 0.125 to 1.0 50 μg/mL	[57]
40	Rhytidhysteron sp. BZM-9	Leptospermum brachyandrum		Euphorbol (91)	MRSA	MIC, 62.5 ug/mL	[58]
41	Stagonosporopsis oculihominis	Dendrobium huoshanense.		Stagonosporopsin C (92)	Staphylococcus aureus subsp. aureus ATCC29213	MIC50, 41.3 μM	[59]
42	Eutypella scoparia SCBG-8.	Leptospermum brachyandrum	SCBG, Chinese Academy of Sciences, China	Eutyscoparols H (93), I (94), tetrahydroauroglaucin (95), flavoglaucin (96)	Staphylococcus aureus and MRSA	MICs in the range of 1.25 to 6.25 μg/mL	[60]
43	Eutypella scoparia SCBG-8	Leptospermum brachyandrum	SCBG, Chinese Academy of Sciences, Guangzhou 510650, China	Eutyscoparin G (97)	S. aureus and MRSA	MIC values of 6.3 μg/mL	[61]
44	Sarocladium oryzae DX-THL3,	Oryza rufipogon Griff.		Sarocladilactone A (98), sarocladilactone B (99), helvolic acid (100), helvolinic acid (101), 6- desacetoxy-helvolic acid (102), 1,2-dihydrohelvolic acid (103)	S. aureus	MIC values of 64, 4, 8, 1, 4 and 16 μg/mL	[62]
				Compound 101	B. subtilis	MIC, 64 μg/mL
				Compounds 99, 101, 103	E. coli	MIC 64 μg/mL each
45	Paraphaeosphaeria sporulosa	Fragaria x ananassa	Caserta province, Southern Italy	Cyclo(L-Pro-L-Phe) (104)	Salmonella strains, S1 and S2	MIC 71.3 and 78.6 μg/mL	[63]
46	Aplosporella javeedii	Orychophragmus violaceus	Beijing, China	Terpestacin (105), fusaproliferin (106), mutolide (108)	M. tuberculosis H37Rv	MICs of 100 μM	[64]
				6,7,9,10-Tetrahydromutolide (107)	S. aureus,	MICs of 100 μM
47	Pleosporales sp. Sigrf05	roots of Siraitia grosvenorii	Guangxi Province of China	Pleospyrone E (109)	B. subtilis, Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas vesicatoria	MIC 100.0µM each	[65]
48	Aplosporella javeedii	Orychophragmus violaceus	Beijing, China	Aplojaveediin A (110)	Staphylococcus aureus strain ATCC 29213, S. aureus strain ATCC 700699 and Bacillus subtilis (ATCC 169)	MICs 50, 50 and 25 μM,	[66]
				Aplojaveediin F (111)	S. aureus ATCC 29213 and ATCC 700699	MICs of 25 and 50 μM
49	Paecilomyces variotii	Lawsonia Alba	University of Karachi, Pakistan	Lawsozaheer (112)	S. aureus (NCTC 6571)	84.26% inhibition at 150 μg/mL	[67]
50	Preussia isomera OSMAC strategy	Panax notoginseng	Wenshan, Yunnan Province, China	Setosol (113)	Multidrug-resistant E. faecium, methicinllin-resistant S. aureus and multidrug-resistant E. faecalis	MIC 25 μg/mL	[68]
	Preussia isomera. XL-1326,	Panax notoginseng		(+)- and (−)-Preuisolactone A (114, 115)	Micrococcus luteus and B. megaterium	MIC, 10.2 and 163.4 μM	[69]
51	Neurospora udagawae	Quercus macranthera	Kaleybar region in northwestern Iran	Udagawanones A (116)	S. aureus	MIC, 66 μg/mL	[70]
52	Xylomelasma sp. Samif07	Salvia miltiorrhiza Bunge		2,6-Dimethyl-5-methoxy-7-hydroxychromone (117), 6-hydroxymethyleugenin (118), 6-methoxymethyleugenin (119), isoeugenitol (120), diaporthin (29), 8-hydroxy-6-methoxy-3-methylisocoumarin (121)	Bacillus subtilis, Staphylococcus haemolyticus, A. tumefaciens, Erwinia carotovora, and Xanthomonas vesicatoria	MIC values at the range of 25 ~ 100 μg/mL	[71]
				2,6-Dimethyl-5-methoxy-7-hydroxychromone (117), diaporthin (29)	B. subtilis, E. carotovora	MIC, 50 and 100 μg/mL
				6-Hydroxymethyleugenin (118), 6-methoxymethyleugenin (119), isoeugenitol (120), diaporthin (29)	S. haemolyticus and E. carotovora	MIC, 75 μg/mL each
				8-Hydroxy-6-methoxy-3-methylisocoumarin (121)	B. subtilis, A. tumefaciens, and X. vesicatoria,	MICs 25, 75, and 25 μg/mL,
53	Amphirosellinia nigrosporaJS-1675	Pteris cretica		(4S,5S,6S)-5,6-epoxy-4-hydroxy-3-methoxy-5-methylcyclohex-2-en-1-one (122)	Acidovorax avenae subsp. cattlyae, Agrobacterium konjaci, A. tumefaciens, Burkholderia glumae, Clavibacter michiganensis subsp. michiganensis, Pectobacterium carotovorum subsp. carotovorum, Pectobacterium chrysanthemi, Ralstonia solanacearum, Xanthomonas arboricola pv. pruni, Xanthomonas axonopodis pv. Citri, Xanthomonas euvesicatoria, Xanthomonas oryzae pv. oryzae	MICs ranging between 31.2 and 500 µg/ml	[72]
54	Emericella sp. XL029	Panax notoginseng		5-(Undeca-3′,5′,7′-trien-1′-yl)furan-2-ol (123) and 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-carbonate (124)	B. subtilis, B. cereus, S. aureus, B. paratyphosum B, S. typhi, P. aeruginosa, E. coli, and E. aerogenes	MIC values ranging from 6.3 to 50 μg/mL	[73]
56	Emericella sp. XL029	Panax notoginseng	Shijiazhuang, Hebei Province, China	14-Hydroxytajixanthone (125), 14- hydroxytajixanthone hydrate (126), 14- hydroxy-15-chlorotajixanthone hydrate (127), 14-methoxytajixanthone-25-acetate (130), questin (132), and carnemycin B (133)	M. luteus, S. aureus, B. megaterium, B. anthracis, and B. paratyphosum B	MIC, in the range of of 12.5 and 25μg/mL	[74]
				Epitajixanthone hydrate (128)	M. luteus, S. aureus, B. megaterium, and B. paratyphosum B	MIC 25 μg/mL
				Tajixanthone hydrate (129), 15-chlorotajixanthone hydrate (131)	S. aureus, B. megaterium, and B. paratyphosum B	MICs 25 and 12.5 μg/mL,
				14-Hydroxytajixanthone (125) Epitajixanthone hydrate (128), carnemycin B (133)	drug resistant S. aureus	MIC 50 μg/mL
				Compounds 125–133	P. aeruginosa, E. coli, and E. aerogenes	MIC 50 μg/mL
57	Byssochlamys spectabilis	Edgeworthia chrysantha	Hangzhou Bay, Hangzhou, Zhejiang Province, China	Bysspectin C (134)	E. coli ATCC 25922 and S. aureus ATCC 25923	MIC, 32 and 64 µg/mL	[75]
58	Poculum pseudosydowianum (TNS-F-57853),	Quercus crispula var. crispula	Yoshiwa, Hatsukaichi, Hiroshima prefecture, Japan	Sydowianumols A (135), and B (136)	MRSA	MIC90 values of 12.5 μg/mL	[76]
59	Lachnum palmae exposure to a HDAC inhibitor SAHA	Przewalskia tangutica	Linzhou Country of the Tibet Autonomous Region, China	Palmaerones A-B, E-G (137, 138, 140, 141, 142)	B. subtilis	MICs, 35, 30, 10, 50, and 55 μg/mL	[77]
				Palmaerones A-C, E (137, 138, 139, 140)	S. aureus	MICs 65, 55, 60, and 55, μg/mL
60	Nemania serpens	Vitis vinifera	Canada’s Niagara region	Nemanifuranone A (143)	E. coli	MIC 200 μg/mL	[78]
					S. aureus, B. subtilis and M. luteus	>75% inhibition at a concentration of 100–200 μg/mL
				Triterpenoid 144	S. cerevisiae	(>25% inhibition) against at 200 μg/mL
					M. luteus	(>75% inhibition) of at a concentration of 100 μg/mL
61	Paraconiothyrium variabile	Cephalotaxus harringtonia		Variabilone (145)	B. subtilis	IC50 of 2.13 μg/mL after 24 h (0.36 μg/mL for kanamycin)	[79]
62	Pyronema sp. (A2-1 & D1-2)	Taxus mairei	Shennongjia National Nature Reserve, Hubei province, China.	Methyl 2-{(E)-2-[4-(formyloxy)phenyl] ethenyl}-4-methyl-3-oxopentanoate (146), (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-perhydro-1,4-oxazine-2,5-dione (147), (3R,6R)-N-methyl-N-(1-hydroxy-2-methylpropyl)-phenylalanine (148), siccanol (149), fusaproliferin (106), and sambutoxin (150)	Mycobacterium marinum ATCCBAA-535,	IC50 of 64, 59, 57, 84, 43 and 32 μM, (positive control rifampin IC50 of 2.1 μM)	[80]
63	Pulvinula sp. 11120	Cupressus arizonica	Tucson, AZ, USA	Pulvinulin A (151), graminin C (152), cis-gregatin B (153), and graminin B (154)	E. coli	12, 18, 16 and14 mm zone of inhibition at 100 μg/mL	[81]
64	Stelliosphaera formicum	Duroia hirsuta	Yasuni’ National Park off the Napo River in Ecuador	Stelliosphaerols A (155) and B (156)	S. aureus	MIC values of 250 μg/mL	[82]
65	Unidentified Ascomycete	Melilotus dentatus		cis-4-Acetoxyoxymellein (157)	E. coli and B. megaterium	Zone of inhibition of 10 and 10 mm (Partial inhibition) at a concentration of 0.05 mg	[83]
				8-Deoxy-6-hydroxy-cis-4-acetoxyoxymellein (158)	E. coli and B. megaterium	Zone of inhibition of 9 and 9 mm (Partial inhibition) at a concentration of 0.05 mg
	Anamorphic Ascomycetes
	Aspergillus
66	Aspergillus sp. FT1307	Heliotropium sp.		Aspochalasin P (159), alatinone (160), β-11-methoxy curvularine (161), 12-keto-10,11-dehydrocurvularine (162)	S. aureus ATCC12600, B. subtilis ATCC6633 and MRSA ATCC43300	MIC in the range of 40 to 80 μg/mL	[84]
67	Aspergillus cristatus	Pinellia ternata		Aspergillone A (163)	B. subtilis and S. aureus	MIC50, 8.5 and 32.2 μg/mL	[85]
68	Aspergillus versicolor strain Eich.5.2.2	Eichhornia crassipes	El-Kanater El-Khayriah in Egypt	22S-Aniduquinolone A (164), 22R-aniduquinolone A (165)	S. aureus (ATCC700699)	MIC, 0.4 μg/mL	[86]
69	Aspergillus versicolor	roots of Pulicaria crispa	Saudi Arabia	Aspergillether B (166)	S. aureus, B. cereus, and E. coli	MICs, 4.3, 3.7, and 3.9 μg/mL	[87]
70	Aspergillus ochraceus SX-C7 eus SX-C7	Setaginella stauntoniana		3-O-β-D-Glucopyranosyl stigmasta-5(6),24(28)-diene (167)	Bacillus subtilis	MIC, 2 μg/mL	[88]
71	Aspergillus amstelodami (MK215708)	Ammi majus	Egypt	Dihydroauroglaucin (168)	E. coli, Streptococcus mutans, S. aureus	MIC, 1.95, 1.95 and 3.9 μg/mL	[89]
					S. aureus, E. coli, Streptococcus mutans, P. aeruginosa	Minimum biofilm inhibitory concentration (MBIC) = 7.81, 7.81, 15.63 and 31.25 μg/mL
72	Aspergillus micronesiensis	Phyllanthus glaucus	LuShan Mountain, Jiangxi Province, China	Cyschalasins A (169) and B (170)	MRSA	MIC50, 17.5 and 10.6 μg/mL: MIC90, 28.4 and 14.7 μg/mL	[90]
73	A. niger	Acanthus montanus	Kala Mountain neighborhood of Yaoundé, Africa	Methylsulochrin (171)	S. aureus, Enterobacter cloacae and Enterobacter aerogenes	MIC, 15.6, 7.8 and 7.8 μg/mL	[91]
74	Aspergillus tubingensis	stem of Decaisnea insignis	Qinling Mountain, Shaanxi Province, China	3-(5-Oxo-2,5-dihydrofuran-3-yl) propanoic acid (172)	Streptococcus lactis	MIC value of 32 μg/mL	[92]
75	Aspergillus flavipes Y-62	Suaeda glauca	Zhoushan coast, Zhejiang province, East China	Methyl 2-(4-hydroxybenzyl)-1,7-dihydroxy-6-(3-methylbut-2-enyl)-1H-indene-1-carboxylate (173)	MRSA	MIC, 128 μg/mL	[93]
					K. pneumoniae and P. aeruginosa	MIC, of 32 μg/mL each
76	Aspergillus sp.	Rhizome of Zingiber cassumunar		4-Amino-1-(1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl)-1H-1,2,3-triazole-5(4H)one (174)	Xanthomonas oryzae, Bacillus subtilis and E. coli	Zone of inhibition 37, 30 and 27 mm	[5]
				3,6-Dibenzyl-3,6-dimethylpiperazine-2,5-dione (175)	E. coli and X. oryzae	Zone of inhibition 21 and 16 mm.
77	Aspergillus fumigatus	Edgeworthia chrysantha	Hangzhou Bay (Hangzhou, China)	Pseurotin A (176), spirotryprostatin A (177)	S. aureus	MIC of 0.39 µg/mL each	[94]
				Spirotryprostatin A (177)	E. coli	MIC, 0.39 µg/mL
78	Aspergillus sp.,	Astragalus membranaceus		Fumiquinazoline J (178), fumiquinazoline C (180), fumiquinazoline H (181), fumiquinazoline D (182)	B. subtilis, S. aureus, E. coli and P. aeruginosa	MICs in the range of 0.5–8 μg/mL	[95]
				Fumiquinazoline I (179), fumiquinazoline B (183)		MICs in the range of 4–16 μg/mL
79	Aspergillus fumigatiaffnis	Tribulus terestris		(−)-Palitantin (184)	E. faecalis UW 2689 and Streptococcus pneumoniae	MIC, 64μg/mL	[96]
80	Aspergillus sp. TJ23	Hypericum perforatum (St John’ Wort)	Shennongjia areas of Hubei Province, China	Aspermerodione (185)	MRSA	MIC, 32 μg/mL/potential inhibitor of PBP2a	[97]
				Andiconin C (186)		marginal antimicrobial activity (>100μg/mL)
81	Aspergillus sp. YXf3	Ginkgo biloba		Prenylterphenyllin D (187), prenylterphenyllin E (188), 2′-O-Methylprenylterphenyllin (189), prenylterphenyllin (190)	X. oryzae pv. oryzicola Swings and E. amylovora	MIC, 20 μg/mL each	[98]
				Prenylterphenyllin B (191)	E. amylovora	MIC, 10 μg/mL
82	Aspergillus sp.	Pinellia ternata	Nanjing, Jiangsu Province, China	Aspergillussanone D (192)	P. aeruginosa, and S. aureus	MIC50, 38.47 and 29.91 μg/mL	[99]
				Aspergillussanone E (193)	E. coli	MIC50, 7.83 μg/mL
				Aspergillussanone F (194)	P. aeruginosa, and S. aureus	MIC50, 26.56, 3.93 and 16.48 μg/mL
				Aspergillussanone G (195)	P. aeruginosa, and S. aureus,	MIC50, 24.46 and 34.66 μg/mL
				Aspergillussanone H (196)	P. aeruginosa, and E. coli,	MIC50, 8.59 and 5.87 μg/mL
				Aspergillussanone I (197)	P. aeruginosa,	MIC50, 12.0 μg/mL
				Aspergillussanone J (198)	P. aeruginosa, E. coli and S. aureus	MIC50, 28.50, 5.34 and 29.87 μg/mL
				Aspergillussanone K (199)	P. aeruginosa, and S. aureus,	MIC50, 6.55 and 21.02 μg/mL
				Aspergillussanone L (200)	P. aeruginosa, S. aureus, and B. subtilis	MIC50, 1.87, 2.77, and 4.80 μg/mL,
				Compound 201	P. aeruginosa, and E. coli,	MIC50, 19.07 and 1.88 μg/mL
83	Aspergillus terreus JAS-2	Achyranthus aspera	Varanasi, India	Terrein (202)	E. faecalis	IC50, 20 μg/mL	[100]
					S. aureus and Aeromonas hydrophila	20 μg/mL
84	Aspergillus terreus	roots of Carthamus lanatus	Al-Azhar University campus in Cairo, Egypt	(22E,24R)-Stigmasta-5,7,22-trien-3-β-ol (203)	MRSA	IC50, 2.29 µM	[101]
85	Aspergillus flavus	Cephalotaxus fortunei	Taibai Mountains, Shaanxi Province, China	5-Hydroxymethylfuran-3-carboxylic acid (204), 5-acetoxymethylfuran-3-carboxylic acid (205)	S. aureus	MIC, 31.3 and 15.6 μg/mL	[102]
86	Aspergillus allahabadii BCC45335	root of Cinnamomum subavenium	Khao Yai National Park, Nakhon Ratchasima Province, Thailand	Allahabadolactone B (206), (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (207)	B. cereus	IC50, 12.50 and 3.13 µg/mL.	[103]
87	Aspergillus tubingensis	Lycium ruthenicum		6-Isovaleryl-4-methoxypyran-2-one (208), asperpyrone A (210), campyrone A (211)	E. coli, Pseudomonas aeruginosa, Streptococcus lactis and S. aureus	MIC values ranging from 62.5 to 500 μg/mL	[104]
				Rubrofusarin B (209)	E. coli	MIC, 1.95 μg/mL
88	Aspergillus tamarii FR02	roots of Ficus carica	Qinling Mountain in China’s Shaanxi province	Malformin E (212)	B. subtilis, S. aureus, P. aeruginosa, and E. coli	MIC, 0.91, 0.45, 1.82, and 0.91 μM	[105]
89	Aspergillus terreus	Roots of Carthamus lanatus	Al-Azhar University campus, Egypt	(22E,24R)-Stigmasta-5,7,22-trien-3-β-ol (203)	MRSA	IC50, 0.96μg/mL	[106]
				Aspernolide F (213)		IC50 6.39μg/mL
90	Aspergillus sp. (SbD5)	Leaves of Andrographis paniculata	Indralaya, Ogan Ilir, South Sumatra.	1-(3,8-Dihydroxy-4,6,6-trimethyl-6H-benzochromen-2-yloxy)propane-2-one (214), 5-hydroxy-4-(hydroxymethyl)-2H-pyran-2-one (215), (5-hydroxy-2-oxo-2H-pyran-4-yl)methyl acetate (216)	S. aureus, E. coli, S. dysenteriae and Salmonella typhi	Zone of inhibition diameters ranging from 8.1 to 12.1 mm at a concentration 500 μg/mL.	[107]
91	Aspergillus sp. IFB-YXS	Ginkgo biloba		Xanthoascin (217)	X. oryzae pv. oryzicola, Swings, E.amylovora, P. syringae pv. Lachrymans and C. michiganense subsp. sepedonicus	MICs, 20, 10, 5.0 and 0.31 µg/mL	[108]
				Prenylterphenyllin B (218)	X. oryzae pv.oryzicola Swings, E.amylovora, P. syringae pv. Lachrymans,	MICs of 20 µg/mL each
				Prenylcandidusin (219)	X. oryzae pv.oryzae Swings X. oryzae pv. oryzicola Swings	MIC values of 10 and 20 µg/mL
	Penicillium
92	Penicillium ochrochloron SWUKD4.1850	Kadsura angustifolia		4-O-Desmethylaigialomycin B (220), penochrochlactones C (221) and D (222)	Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa	MIC values between 9.7 and 32.0 μg/mL	[109]
93	Penicillium brefeldianum	Syzygium zeylanicum		p-Hydroxybenzaldehyde (223),	S. typhi, E. coli, and B. subtilis	MIC values of 64 g/mL	[110]
94	Penicillium vulpinum GDGJ-91	Sophorae tonkinensis	Baise, Guangxi Province, China	10-Demethylated andrastone A (224), andrastin A (227)	Bacillus megaterium	MIC value of 6.25 μg/mL	[111]
				Citreohybridone E (225), citreohybridonol (226), citreohybridone B (228)	B. megaterium	MIC values of 25, 12.5 and 25 μg/mL
				Citreohybridonol (226)	B. paratyphosus B, E. coli and S. aureus	MIC, 6.25, 25 and 25 μg/mL
				10-Demethylated andrastone A (224), citreohybridone E (225), andrastin A (227), andrastin B (228)	B. paratyphosus B	MIC, 12.5 or 25 μg/mL.
95	Penicillium nothofagi P-6,	Abies beshanzuensis	Baishanzu Mountain in Lishui, Zhejiang Province of China	Chromenopyridin A (229), viridicatol (230)	S. aureus ATCC29213	MIC, 62.5 and 15.6 μg/mL	[112]
96	Penicillium restrictum (strain G85)	Silybum marianum	Horizon Herbs, LLC (Williams, OR, USA).	ω-Hydroxyemodin (231)	Clinical isolates of MRSA	Quorum-sensing inhibition in both in vitro and in vivo models	[113]
97	Penicillium vulpinum	S. tonkinensis	Baise, Guangxi Province, China	(−)-3-Carboxypropyl-7-hydroxyphthalimide (232)	Shigella dysenteriae and Enterobacter areogenes	MIC, 12.5 μg/mL each	[114]
					B. subtilis	MIC, 25 μg/mL
					B. megaterium and Micrococcus lysodeikticus	MIC, 50 μg/mL
				(−)-3-Carboxypropyl-7-hydroxyphthalide methyl ester (233)	E. areogenes	MIC, 12.5 μg/mL
					B. subtilis, B. megaterium and M. lysodeikticus	MIC, 100 μg/mL.
98	Penicillium sumatrense GZWMJZ-313	Leaf of Garcinia multiflora	Libo, Guizhou Province of China	Citridone E (234), (–)-dehydrocurvularin (235)	S. aureus, P. aeruginosa, Clostridium perfringens, and E. coli	MIC values ranging from 32 to 64 μg/mL	[115]
99	Penicillium ochrochloronthe	Roots of Taxus media	Qingfeng Mountain, Chongqing, China	3,4,6-Trisubstituted α-pyrone derivatives, namely 6-(2′R-hydroxy-3′E,5′E-diene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (236), 6-(2′S-hydroxy-5′E-ene-1′-heptyl)-4-hydroxy-3-methyl-2H-pyran2-one (237), 6-(2′S-hydroxy-1′-heptyl)-4 -hydroxy-3-methyl-2H-pyran-2-one (238), trichodermic acid (239)	B. subtilis, Micrococcus luteus, S. aureus, B. megaterium, Salmonella enterica, Proteusbacillm vulgaris, Salmonella typhi, P. aeruginosa, E. coli and Enterobacter aerogenes	MIC values ranging from 25 to 50 μg/mL	[116]
100	Penicillium janthinellum SYPF 7899	Panax notoginseng	Wenshan region, Yunnan province, China	Brasiliamide J-a (240), brasiliamide J-b (241)	B. subtilis and S. aureus	MIC, 15 and 18 μg/mL,	[117]
				Peniciolidone (242), austin (243)	B. subtilis	MIC, 35 and 50 μg/mL
					S. aureus	MIC 39, and 60 μg/mL
101	Penicillium cataractum SYPF 7131	Ginkgo biloba		Penicimenolidyu A (244), penicimenolidyu B (245) and rasfonin (246)	S. aureus	MIC 65, 59 and 10 μg/mL	[118]
102	Penicillium sp.,	Tubers of Pinellia ternata	suburb of Nanjing, Jiangsu, China.	3′-Methoxycitreovirone (247), citreovirone (249)	E. coli and S. aureus	MIC = 62.6 and 76.6 μg/mL	[119]
				Helvolic acid (100)	S. aureus, P. aeruginosa, B. subtilis and E. coli	MIC = 5.8, 4.6, 42.2 and 75.0 μg/mL
				cis-bis-(Methylthio)-silvatin (248), trypacidin A (250)	S. aureus	MIC values of 43.4 and 76.0 μg/mL
				Trypacidin A (250)	B. subtilis	MIC = 54.1 μg/mL
103	Penicillium sp. R22	Nerium indicum	Qinling Mountain, Shaanxi Province, China	Viridicatol (251)	S. aureus	MIC value of 15.6 μg/mL	[120]
104	Penicillium sp. (NO. 24)	Tapiscia sinensis	Shennongjia National Forest Park China	Penicitroamide (252)	Erwinia carotovora subsp. Carotovora	MIC50 at 45 μg/mL	[121]
105	Penicillium sp. CAM64	Leaves of Garcinia nobilis	Mount Etinde, Southwest region Cameroon	Penialidin A (253)	Vibrio cholerae SG24 (1), V. cholerae CO6, V. cholerae NB2, V. cholerae PC2, S. flexneri SDINT,	MIC, 8–32 μg/mL	[122]
				Penialidin B (254)		MIC, 4–32 μg/mL
				Penialidin C (255)		MIC, 0.50, 16, 8, 0.50 and 8 μg/mL
				Citromycetin (256), brefelfin A (258)		MIC, 64–128 μg/mL
				p-Hydroxyphenylglyoxalaldoxime (257)		MIC, 32–64 μg/mL
106	Purpureocillium lilacinum	roots of Rauvolfia macrophylla	Mount Kalla in the Center Region of Cameroon	Purpureone (259)	B. cereus, L. monocytogenes, E. coli ATCC 8739, K. pneumoniae ATCC 1296, P. stuartii ATCC 29916, P. aeruginosa ATCC PA01	Zone of inhibition of 10.6, 12.3, 13.0, 8.7, 12.3, and 10.0, mm against (10 μL/6 mm Filter paper disks).	[123]
	Fusarium
	Neocosmospora sp. MFLUCC 17-0253	Rhizophora apiculate.		Mixture of 2-methoxy-6-methyl-7-acetonyl-8-hydroxy-1,4-naphthalenedione (260), and 5,8-dihydroxy-7-acetonyl-1,4-naphthalenedione (261)	Acidovorax citrulli	MIC value of 0.0075 mg/mL	[124]
				Anhydrojavanicin (262)		0.004 mg/mL
				Fusarnaphthoquinone (263)		0.025 mg/mL
107	Fusarium sp.	Mentha longifolia	Al Madinah Al Munawwarah, Saudi Arabia.	Fusaribenzamide A (264)	S. aureus and E. coli	MICs, 62.8 and 56.4 μg/disc	[125]
108	F. proliferatum AF-04	Green Chinese onion		5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	B. megaterium	MICs 25 μg/mL each.	[126]
				5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272)	B. subtilis	MICs, 50 μg/mL each.
				Indol-3-acetic acid (265), beauvericin (267), epicyclonerodiol oxide (269)	B. megaterium	MICs 50 μg/mL each
				Cyclonerodiol (268)	B. megaterium	MIC 12.50 μg/mL.
				epi-Cyclonerodiol oxide (269), methyl ether fusarubin (272)	E. coli	MIC 50 μg/mL
				5-O-Methylsolaniol (270), 5-O-methyljavanicin (271), anhydrojavanicin (273)	E. coli	MIC 25 μg/mL
				epi-Cyclonerodiol oxide (269), 1,4-naphthoquinones, 5-O-methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272)	Clostridium perfringens	MICs 50, 50, 12.5 and 50 μg/mL
				Beauvericin (267), fusaproliferin (106), 5-O-methylsolaniol (270), 5-O-methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	MRSA	MIC value of 50, 50, 12.5, 12.5, 12.5, and 25 μg/mL respectively.
				5-O-Methyljavanicin (271), methyl ether fusarubin (272), anhydrojavanicin (273)	RN4220	MIC value of 50 μg/mL each.
				Methyl ether fusarubin (272), anhydrojavanicin (273)	NewmanWT	MIC value of 50 μg/mL each.
				Bassiatin (266)	NewmanWT	MIC, 50 μg/mL
109	Fusarium sp. TP-G1	Dendrobium officinable	Chongqing Academy of Chinese Materia Medica in China	Trichosetin (274), beauvericin (267), beauvericin A (275), enniatin H (277), enniatin I (278), enniatin MK1688 (279)	S. aureus and MRSA	IC50 values in the range of 2–32 μg/mL	[127]
				Enniatin B (276)	S. aureus and MRSA	IC50, 128 μg/mL each
				Fusaric acid (280), dehydrofusaric acid (281)	Acinetobacter baumannii	MIC, 64 and 128 μg/mL
	Fusarium sp. YD-2	Santalum album	Dongguan, Guangdong Province, China	Fusariumin A (282)	S. aureus and P. aeruginosa	MIC, 6.3 μg/mL	[128]
				Asperterpenoid A (283)	Salmonella enteritidis and Micrococcus luteus	MIC, 25.2 and 6.3 μg/mL
				Agathic acid (284)	B. cereus and M. luteus	MIC, 12.5 and 25.4 μg/mL
110	Fusarium chlamydosporium	Leaves of Anvillea garcinii	Al-Azhar University campus, Egypt	Fusarithioamide B (285)	E. coli, B. cereus, and S. aureus	MIC value of 3.7, 2.5 and 3.1 µg/mL	[129]
111	Fusarium solani A2	Glycyrrhiza glabra	Kashmir Himalayas of Jammu and Kashmir State, India	3,6,9-Trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]-isochromene-5,10-dione (286), fusarubin (287), 3-O-methylfusarubin (288), javanicin (289)	S. aureus (MTCC 96), K. pneumonia (MTCC 109), S. pyogenes (MTCC 442), B. subtilis (MTCC 121), B. cereus (IIIM 25), Micrococcus luteus (MTCC 2470) and E. coli (MTCC 730)	MIC values in the range of <1 to 256 μg/mL.	[130]
				Fusarubin (287)	Mycobacterium tuberculosis strain H37Rv	MIC, 8 μg/mL,
				3,6,9-Trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]-isochromene-5,10-dione (286), 3-O-methylfusarubin (288), javanicin (289)		MIC values of 256, 64, 32 μg/mL
112	Fusarium chlamydosporium	Anvillea garcinii	Al-Azhar University, Saudi Arabia	Fusarithioamide A (290)	B. cereus, S. aureus, and E. coli	MICs values of 3.1, 4.4, and 6.9 μg/mL	[131]
113	Fusarium sp.	Rhoeo spathacea	Pondok Cabe, Banten, Indonesia.	Javanicin (289)	M. tuberculosis and M. phlei	MIC 25 and 50 μg/mL	[132]
114	Fusarium sp.	Ficus carica	Qinling Mountain, Shaanxi Province, China	Helvolic acid Me ester (291)	B. subtilis, S. aureus, E. coli and P. aeruginosa	MIC, 6.25, 12.5, 6.25, and 3.13 μg/mL	[133]
				Helvolic acid (100)		MICs 6.25, 6.25, 6.25, and 3.13 μg/mL
				hydrohelvolic acid (292)		MICs 6.25, 12.5, 6.25, and 3.13 μg/mL
115	Fusarium sp.	-	-	Colletorin B (293), 4,5-dihydroascochlorin (294)	B. megaterium	5 and 10 mm zone of inhibition at 10 μg/mL concentration of	[134]
116	Fusarium sp.	Opuntia dillenii	South-Eastern arid zone of Sri Lanka	Equisetin (295)	B. subtilis	MIC, 8 μg/mL	[135]
					S. aureus and MRSA.	MIC, 16 μg/mL
117	Trichoderma harzianum	Zingiber officinale	Banyumas, Central Java, Indonesia	Pretrichodermamide A (296)	M. tuberculosis	MIC, 25 μg/mL (50 μM)	[136]
118	Trichoderma koningiopsis YIM PH30002	Panax notoginseng		Koninginin W (297), koninginin D (298), 7-O- and koninginin A (301)	B. subtilis	MIC of 128 μg/mL.	[137]
				Koninginin W (297), 7-O-methylkoninginin D (299)	S. typhimurium	MIC, 64 and 128 μg/mL;
				Koninginin W (297), koninginin (300)	E. coli	MIC of 128 μg/mL.
119	Trichoderma virens QA-8	Artemisia argyi		Trichocarotins I–M (302–306), CAF-603 (307), 7β-hydroxy CAF-603 (308), trichocarotins E–H (309–312), and trichocarane A (313)	E. coli EMBLC-1,	MIC values ranging from 0.5 to 32 µg/mL MIC = 0.5 µg/mL	[138]
				7β-Hydroxy CAF-603 (308)	Micrococcus luteus QDIO-3
120	Trichoderma koningiopsis QA-3	Artemisia argyi.		Trichodermaketone E (314), trichopyranone A (316), 3-hydroxyharziandione (317) and 10,11-dihydro-11-hydroxycyclonerodiol (318), harziandione (321)	E. coli	MIC values ranging from 0.5 to 64 μg/mL	[139]
				Trichopyranone A (316), 3-hydroxyharziandione (317), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	M. luteus	MIC values ranging from 1 to 16 μg/mL
				Trichodermaketone E (314), 4-epi-7-O-methylkoninginin D (315), 3-hydroxyharziandione (317), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	P. aeruginosa	with MIC values ranging from 4 to 16 μg/mL
				Trichodermaketone E (314), 10,11-dihydro-11-hydroxycyclonerodiol (318), cyclonerodiol (319), 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one (320), harziandione (321)	V. parahaemolyticus	MIC values ranging from 4 to 16 μg/mL.
				3-Hydroxyharziandione (317)	E. coli	MIC value of 0.5 µg/mL
				6-(3-Hydroxypent-1-en-1-yl)-2H-pyran-2-one (320)	M. luteus	MIC value of 1 µg/mL
121	Trichoderma koningiopsis QA-3	Artemisia argyi	Qichun of the Hubei Province, China	15-Hydroxy-1,4,5,6-tetra-epi-koninginin G (322)	Vibrio alginolyticus	MIC, 1 μg/mL	[140]
				Koninginin U (323), 14-ketokoninginin B (324)	Vibrio harveyi and Edwardsiella tarda	MICs 4 and 2 µg/mL
122	Trichoderma atroviride B7	Colquhounia coccinea var. mollis	Kunming Botanical Garden, Yunnan, China	Harzianol I (325)	S. aureus, B. subtilis, and M. luteus	EC50 7.7, 7.7, and 9.9 μg/mL	[141]
123	Trichoderma longibrachiatum MD33	Dendrobium nobile	Jinshishi, Chishui, China	Dendrobine (326)	Bacillus mycoides, B. subtilis, and Staphylococcus	Zone of inhibition of 9, 12 and 8 mm	[142]
124	Trichoderma virens QA-8,	Artemisia argyi	Qichun of Hubei Province in central China	Trichocadinins B-D and G (327–330)	E. coli EMBLC-1, Aeromonas hydrophilia QDIO-1, Edwardsiella tarda QDIO-2, E. ictarda QDIO-10, Micrococcus luteus QDIO-3, P. aeruginosa QDIO-4, Vibrio alginolyticus QDIO-5, V. anguillarum QDIO-6, V. harveyi QDIO-7, V. parahemolyticus QDIO-8, and V. vulnificus QDIO-9	MIC in the range of 8–64 μg/mL	[143]
				Trichocadinin G (330)	Ed. tarda and V. anguillarum	MIC values of 1 and 2 μg/mL
125	Trichoderma koningiopsis A729	Morinda officinalis		Koninginols A-B (331–332)	B. subtilis	MIC values of 10 and 2 μg/mL	[144]
126	Trichoderma koningiopsis QA-3	Artemisia argyi	Qichun	Ent-koninginin A (333)	V. vulnificus	MIC, 4 μg/mL	[145]
				Ent-koninginin A (333), trichoketide A (339)	E. coli, E. tarda, V. anguillarum, and V. parahemolyticus	MICs ranging from 8 to 64 μg/mL
				Ent-koninginin A (333), 1,6-di-epi-koninginin A (334), 15-hydroxykoninginin A (335), 10-deacetylkoningiopisin D (336), koninginin T (337), koninginin L (338), trichoketide A (339)	E. coli	MIC, 64 μg/mL each
					E. tarda, V. alginolyticus, and V. anguillarum	MIC values ranging from 4 to 64 μg/mL
	Alternaria
127	Alternaria alternata ZHJG5	Cercis chinensis		Isotalaroflavone (340), 4-hydroxyalternariol-9-methyl ether (341), verrulactone A (342)	Xanthomonas oryzae pv. Oryzae, Xanthomonas oryzae pv. oryzicola and Ralstonia solanacearum (Rs)	MIC ranging from 0.5 to 64 μg/mL.	[146]
128	Alternaria sp. PfuH1	Pogostemon cablin (Pacholi).		Alternariol (44), altertoxin VII (343), altenuisol (344)	S. agalactiae	MIC, 9.3, 17.3 and 85.3 μg/mL	[147]
				Altenuisol (344)	E. coli	MIC, 128 μg/mL
129	Alternaria alternata ZHJG5	Cercis chinensis		Alternariol (44), altenuisol (344), alterlactone (345), Dehydroaltenusin (346)	FabH of Xanthomonas oryzae pv. oryzae (Xoo)	IC50 values from 29.5 to 74.1 μM	[148]
					Xanthomonas oryzae pv. Oryzae	MIC values from 4 to 64 μg/mL.
				Alternariol (44), alterlactone (345)	Rice bacterial leaf blight	a protective efficiency of 66.2 and 82.5% at the concentration of 200 μg/mL
130	Alternaria alternata MGTMMP031	Vitex negundo	Madurai, Tamil Nadu, India	Alternariol Me ether (347)	B. cereus, Klebsiella pneumoniae	MIC, 30 µM/L	[149]
					E. coli, Salmonella typhi, Proteus mirabilis, S. aureus and S. epidermidis	MIC, 35 µM/L
131	Alternaria alternata	Grewia asiatica		3,7-Dihydroxy-9-methoxy-2-methyl-6H-benzo[c]chromen-6-one (348)	S. aureus (ATCC 29213), VRE, and MRSA	MIC, 32, 32 and 8 μg/mL	[150]
				Alternariol (44)	S. aureus (ATCC 29213), VRE, and MRSA	MIC, 128, 128, and 64 μg/mL
132	Alternaria sp. Samif01	Salvia miltiorrhiza	Beijing Medicinal Plant Garden, Beijing, China	Altenuisol (344), 4-hydroxyalternariol-9-methyl ether (349) and alternariol (44)	A. tumefaciens, B. subtilis, Pseudomonas lachrymans, Ralstonia solanacearum, Staphylococcus hemolyticus and Xanthomonas vesicatorya	MIC values in the range of 86.7–364.7 μM	[151]
133	Alternaria sp. Samif01	Salvia miltiorrhiza	Beijing, China	Alternariol 9-Me ether (347)	Bacillus subtilis ATCC 11562 and Staphylococcus haemolyticus ATCC 29970, A. tumefaciens ATCC 11158, Pseudomonas lachrymans ATCC 11921, Ralstonia solanacearum ATCC 11696, and Xanthomonas vesicatoria ATCC 11633	IC50 values varying from 16.00 to 38.27 g/mL	[152]
134	Alternaria sp. and Pyrenochaeta sp.,	Hydrastis canadensis	William Burch in Hendersonville, North Carolina	Altersetin (350), macrosphelide A (351)	S. aureus	MIC, 0.23, and 75 μg/mL	[153]
135	Simplicillium lanosoniveum	Hevea brasiliensis	Songkhla Province, Thailand	Simplicildones K (352)	S. aureus ATCC25923, MRSA	MIC, 128μg/mL	[154]
				Botryorhodine C (353), simplicildones A (354)	S. aureus ATCC25923, MRSA	MIC, 32 μg/mL each
136	Simplicillium sp. PSU-H41	Hevea brasiliensis	Songkhla Province, Thailand	Botryorhodine C (353), simplicildone A (354)	S. aureus	MIC, 32 μg/mL each	[155]
				Botryorhodine C (353)	MRSA	MIC, 32 μg/mL
	Cladosporium
137	Cladosporium cladosporioides	Zygophyllum mandavillei	Al-Ahsa, Saudi Arabia	Isocladosporin (355), 5′- hydroxyasperentin (356), 1-acetyl-17-methoxyaspidospermidin-20-ol (357), and 3-phenylpropionic acid (358)	Xanthomonas oryzae and Pseudomonas syringae	MIC values in the range of 7.81 to 125 µg/mL	[156]
138	Cladosporium sphaerospermum WBS017	Fritillaria unibracteata var. wabuensis	Western Sichuan Plateau of China	Cladosin L (359)	S. aureus ATCC 29213 and S. aureus ATCC 700699	MICs, 50 and 25 mM,	[157]
139	Cladosporium sp.	Rauwolfia serpentina		Me ether of fusarubin (360)	S. aureus, E. coli, P. aeruginosa and B. megaterium	Zone of inhibition of 27, 25, 24 and 22 mm (40μg/disk)	[158]
	Pestalotiopsis
140	Pestalotiopsis sp. M-23	Leucosceptrum canum	Kunming Botanical Garden, China	11-Dehydro-3a-hydroxyisodrimeninol (361)	B. subtilis	IC50, 280.27 µM	[159]
141	Pestalotiopsis sp.	Melaleuca quinquenervia	Toohey Forest, Queensland, Australia	(1S,3R)-austrocortirubin (362), (1S,3S)-austrocortirubin (363), 1-deoxyaustrocortirubin (364)	Gram-pos.	100 μM	[160]
142	Neopestalotiopsis sp.			Neopestalotins B (365)	B. subtilis, S. aureus, S. pneumoniae	MIC, 10, 20, and 20 μg/mL	[161]
	Phoma
143	Phoma cucurbitacearum	Glycyrrhiza glabra	Jammu (J&K).	Thiodiketopiperazine derivatives (366) and (367)	S. aureus and Streptococcus pyogenes	IC50, 10 μM	[162]
144	Phoma sp. JS752	Phragmites communis	Seochun, South Korea	Barceloneic acid C (368)	Listeria monocytogenes and Staphylococcus pseudintermedius	MIC, 1.02 μg/mL each	[163]
145	Setophoma sp.,	Psidium guajava fruits		Thielavins T (369), U (370) and V (371)	S. aureus ATCC 25923	MIC, 6.25, 50, and 25 μg/mL	[164]
	Colletotrichum
146	Colletotrichum gloeosporioides B12	Illigera rhodantha	Qionghai City, Hainan Province, China	Colletolides A (372) and B (373), and 3-methyleneisoindolinon (374)	Xanthomonas oryzae pv. oryzae,	MIC, 128 μg/mL each	[165]
				Sclerone (375)	X. oryzae pv. oryzae	MIC, 64 μg/mL
147	Colletotrichum sp. BS4	Buxus sinica	Guangzhou, Guangdong Province, China	Colletotrichones A (376)	E. coli and B. subtilis	MIC, 1.0 and 0.1 μg/mL	[166]
				Colletotrichone B (377)	S. aureus (DSM 799)	MIC, 5.0 μg/mL
				Colletotrichone C (378)	E. coli	MIC, 5.0 μg/mL
	Minor Taxa of Anamorphic Ascomycetes
148	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	Agricultural University Beijing China	Rhizopycnolide A (379)	A. tumefaciens, B. subtilis, and P. lachrymans	MICs 100, 75, and 100 μg/mL	[167]
				Rhizopycnin C (380), penicilliumolide D (384), alternariol (44)	A. tumefaciens, B. subtilis, Pseudomonas lachrymans, Ralstonia solanacearum, Staphylococcus hemolyticus, and Xanthomonas vesicatoria,	MICs in the range 25–100 μg/mL
				Rhizopycnin D (381)	A. tumefaciens, B. subtilis, and R. solanacearum,	MIC 50 μg/mL each,
					X. vesicatoria	MIC, 75 μg/mL.
				Palmariol B (383), Alternariol 9-methyl ether (347)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, and X. vesicatoria,	IC50 values in the range 16.7−34.3 μg/mL
				TMC-264 (382)	B. subtilis	MIC 50 μg/mL
149	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	China Agricultural University, Beijing	Rhizoperemophilane K (385), 1α-hydroxyhydroisofukinon (386), 2-oxo-3-hydroxyeremophila-1(10),3,7(11), 8-tetraen-8,12-olide (387)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. haemolyticus, and X. vesicatoria,	MIC, 32~128 μg/mL	[168]
150	Rhizopycnis vagum Nitaf22 (synonym Acrocalymma vagum)	Nicotiana tabacum	China Agricultural University (CAU), Beijing 100101, China	Rhizopycnis acid A (388)	A. tumefaciens, B. subtilis, P. lachrymans, R. solanacearum, S. hemolyticus and X. vesicatoria	MICs, 20.82, 16.11, 23.48, 29.46, 21.11, and 24.31 µg/mL	[169]
				Rhizopycnis acid B (389)		MICs, 70.89, 81.28, 21.23, 43.40, 67.61, and 34.86 µg/mL
151	Leptosphaeria sp. XL026	Panax notoginseng	Shijiazhuang, Hebei province, China	Leptosphin B (390), conidiogenone C (391), conidiogenone D (392), conidiogenone G (393)	B. cereus	MICs 12.5–6.25 μg/mL	[170]
				Conidiogenone D (392)	P. aeruginosa	MIC, 12.5 μg/mL
152	Lophiostoma sp. Eef-7	Eucalyptus exserta.		Scorpinone (394), 5-deoxybostrycoidin (395)	Ralstonia solanacearum	Zone of inhibition of 9.86 and 9.58 mm at 64 µg concentration	[171]
	Lophiostoma sp. Sigrf10	Siraitia grosvenorii	Guangxi Province of China	(8R,9S)-dihydroisoflavipucine (396), (8S,9S)-dihydroisoflavipucine (397)	B. subtilis, A. tumefaciens, Ralstonia solanacearum, and Xanthomonas vesicatoria	IC50 in the range of 35.68–44.85 µM	[172]
153	Cytospora chrysosperma	Hippophae rhamnoides		Cytochrysin A (398)	Enterococcus faecium	MIC, 25 μg/mL	[173]
				Cytochrysin C (399)	MRSA	MIC, 25 μg/mL
154	Microsphaeropsis sp. Seimatosporium sp.	Salsola oppositifolia	Gomera, Spain	Microsphaerol (400)	B. megaterium and E. coli,	Zone of inhibition 8 and 9 mm at 0.05 mg concentration	[174]
				Seimatorone (401)	B. megaterium and E. coli,	Zone of inhibition 3 and 7 (partial) mm at a 0.05 mg concentration
155	Epicoccum nigrum MK214079	Salix sp.	Caucasus mountains Lago-Naki, Russia	Epicocconigrone A (402), epipyrone A (403), and epicoccolide B (404)	S. aureus ATCC 29213	MIC values ranging from 25 to 50 μM	[175]
156	Epicoccum nigrum	Entada abyssinica	Balatchi (Mbouda), in the West region of Cameroon	p-Hydroxybenzaldehyde (223)	S. aureus, B. cereus, P. aeruginosa, and E. coli	MICs 50, 25, 50, and 25 µg/mL	[176]
				Beauvericin (267)	S. aureus, B. cereus, and Salmonella typhimurium	MICs 3.12, 12.5, and 12.5 µg/mL
				Indole-3-carboxylic acid (405)	S. aureus and E. faecalis	MIC values of 6.25 and 50 µg/mL
				Quinizarin (406)	S. aureus, B. cereus St	MIC values of 50 µg/mL each
157	Stemphylium lycopersici	S. tonkinensis		Xylapeptide B (407)	B. subtilis, S. aureus and E. coli	MIC, 12.5, 25 and 25 μg/mL	[177]
				Cytochalasin E (408)	B. subtilis, S. aureus, B. anthracis, S. dysenteriae, and E. coli	MIC 12.5 to 25 μg/mL
				6-Heptanoyl-4-methoxy-2H-pyran2-one (409)	S. paratyphi B	MIC, 12.5 μg/mL
				(–)-5-Carboxymellein (410)	B. subtilis, S. aureus, B. anthracis, S. dysenteriae, S. paratyphi, E. coli and S. paratyphi B	MIC values from 12.5 to 25 μg/mL
158	Stemphylium globuliferum,	Juncus acutus	Egypt	Dihydroaltersolanol C (411)	S. aureus	MICs of 49.7 μM	[178]
159	Lecanicillium sp. (BSNB-SG3.7 Strain)	Sandwithia guyanensis	St Elie, France.	Stephensiolides I (412), D (413), G (414), stephensiolide F (415)	MRSA	MICs 4, 32, 16 and 32 μg/mL	[179]
160	Nigrospora sphaerica	Adiantum philippense	Western Ghats region near Virajpete, India	Phomalactone (416)	E. coli and X. campestris	MIC 3.12 μg/mL	[180]
					S. typhi, B. subtilis, B. cereus, and K. pneumonia	MIC value of 6.25 μg/mL
					S. aureus, S. epidermidis, and C. albicans	MIC of 12.5 μg/mL
161	Nigrospora sp. BCC 47789	Choerospondias axillaris	Khao Yai National Park, Nakhon Ratchasima Province, Thailand	Nigrosporone B (417)	M. tuberculosis, B. cereus and E. faecium	MICs 172.25, 21.53 and 10.78 μM	[181]
162	Curvularia sorghina BRIP 15900)	Rauwolfia macrophylla	Mount Kalla in Cameroon	2′-Deoxyribolactone (419), hexylitaconic acid (419)	E. coli, Micrococcus luteus, Pseudomonas agarici and Staphylococcus warneri	MIC ranging between 0.17 μg/mL and 0.58 μg/mL	[182]
163	Curvularia lunata	Paepalanthus chiquitensis	Serra do Cipó, in Minas Gerais State, Brazil	Triticones E (420), F (421)	E. coli,	MIC 62.5 μg/mL	[183]
164	Bipolaris sp. L1-2	Lycium barbarum	Ningxia Province, China	Cochlioquinones B (422), C (423), isocochlioquinones (424)	B. subtilis, C. perfringens, and P. viridiflava	MICs 26 μM	[184]
165	Bipolaris eleusines	Potatoes	nursery of Yunnan Agricultural University, Kunming, Yunnan China	(S)-5-Hydroxy-2-(1-hydroxyethyl)-7-methylchromone (425), 5,7-dihydroxyl-2,6,8-trimethylchromone (426)	Staphylococcus aureus subsp. Aureus	inhibition rates of 56.3 and 32 %, at the concentration of 128 μg/mL	[185]
166	Bionectria sp. Y1085,	Huperzia serrata	Xichou County, Yunnan Province, China	Bionectin D (427), bionectin E (428), verticillin A (430), sch 52901 (429), gliocladicillin C (431)	E. coli, S. aureus, and S. typhimurium ATCC 6539,	MIC values ranging from 6.25–25 µg/mL	[186]
167	Cylindrocarpon sp.,	Sapium ellipticum	Haut Plateaux region, Cameroon	Pyrrocidine A (432)	S. aureus, ATCC 25923, S. aueus ATCC 700699, S. aueus ATCC 700699, E. faecalis ATCC 29212, E. faecalis ATCC 51299, E. faecium ATCC 35667, E. faecium ATCC 700221	MIC values ranging from 0.78 to 25 μM	[187]
				19-O-Methylpyrrocidine B (433)	S. aureus ATCC25923 and ATCC700699	MIC, 50 and 25 μM,
168	Eupenicillium sp. LG41.9 treated with HDAC inhibitor, nicotinamide (15 mg/100 mL)	Xanthium sibiricum	Taian, Shandong Province, China	Eupenicinicol C (434)			[188]
				Eupenicinicol D (435),	S. aureus	MIC 0.1 μg/mL,
				Eujavanicol A (436)	E. coli	MIC 5.0 μg/mL
				Eupenicinicol A (437)
169	Dendrothyrium variisporum	Globularia alypum	Ain Touta, Batna 05000, Algeria	2-Phenylethyl 3-hydroxyanthranilate (438)	B. subtilis and M. luteus	MICs 8.33 and 16.66 μg/mL	[189]
				2-Phenylethyl anthranilate (439)	B. subtilis and M. luteus	66.67 μg/mL each
170	Exserohilum rostratum	Phanera splendens (Kunth) Vaz		Ravenelin (440)	Bacillus subtilis and Staphylococcus aureus	MICs, 7.5 and 484 μM	[190]
171	Exserohilum rostratum	Bauhinia guianensis		Monocerin (441)	P. aeruginosa	MIC, 62.5 µg/mL	[191]
				Annularin I (442)	E. coli and B. subtilis	MIC, 62.50 and 31.25 µg/mL
				Annularin J (443)	E. coli and B. subtilis	MIC, 62.50 µg/mL each
	Basidiomycete
172	Psathyrella candolleana	Ginkgo biloba		Quercetin (444), carboxybenzene (445), and nicotinamide (446)	S. aureus	MIC 0.3906, 0.7812 and 6.25 μg/mL	[192]
173	Irpex lacteus DR10-1	Distylium chinense	Banan district of Chongqing in the TGR area, China	Irpexlacte A (447), irpexlacte B-D (448–450)	P. aeruginosa	MIC values ranging from 23.8 to 35.4 μM	[193]
	Zygomycetes
174	Mucor irregularis			Chlorflavonin (451)			[194]

4. Methods Used for Activation of Silent Biosynthetic Genes

It has been reported that fungi have various unexpressed gene clusters related to bioactive secondary metabolites, which do not express in mass multiplications of the axenic form [213,214]. The expression of such gene clusters directly or indirectly depends on the surrounding environment of the microorganism. In axenic form, various induction or activation signals are or may be absent for some bioactive molecule production in the culture, which are usually present in natural habitats [215]. Such biosynthetic gene clusters (BGC) are part of the heterochromatin of fungal chromosomes, which do not express at laboratory conditions [216].

To induce such silent biosynthetic gene clusters two major approaches have been reported, including pleiotropic- and pathway-specific approaches, which include various techniques like knocking down, mutation induction [217], co-culture methods [218], heterologous expression [219,220], interspecies crosstalk [221], one strain many compounds (OSMAC) [222] and epigenetic manipulation [223]. Changes in media composition and physical factors like pH, temperature, light, salt concentration, metal and elicitor also support the induction of silent BGC and improve production of secondary metabolites in microbes. The generation of various types of stresses significantly affects the metabolic activities of growing culture and microbes to release compounds for their survival under stress conditions. Changes in physical conditions or stresses impacted gene regulation by upregulating or downregulating the gene expression [126,224]. Nowadays, high throughput elicitor screening technique (HiTES) is also employed to save time in exposing culture against various types of elicitors. In this technique selected culture is grown in 96 well plates with various elicitors in each well and after the incubation period metabolites are identified by mass spectrometry or assay system.

The mutation is one of the other approaches to induce silent biosynthetic gene clusters (BGC). Mutation in RNA polymerase genes and ribosomal proteins changes the transcription and translational process and upregulates the expression of biosynthetic gene clusters. Some of the genes related to biosynthetic gene clusters are silent from decades and overexpression of adpA, a global regulatory gene, induced the expression of silent lucensomycin in Streptomyces cyanogenus S136 [225]. Cloning is another type of molecular technique used to express the silent BGC incompatible strains. In the cloning method, isolation of high-quality DNA, fragmentation, library construction and development of suitable expression vectors for large sequences of BGC is a challenging task and many groups are working on this aspect [226]. In addition to this, use of bioinformatics also helps in direct cloning of silent BGCs and their expression for secondary metabolites production. Development of various bioinformatics tools such as PRISM3, BiG-SCAPE and anti-SMASH etc facilitated the scientist to identify bioactive gene clusters in unknown strains without time consumption used in identification of active BGC sites [227]. The CRISPR-Cas system is also a excellent tool for cloning system or genome editing that provides better expression of silent BGC in comparison to conventional molecular techniques [228]. Similarly, promoter engineering, transcriptional regulation engineering and ribosome engineering also support the activation of silent BGC through molecular approaches [229]. Recent use of Cpf1 nuclease in genome editing was also found to be a suitable tool for induction of silent BGC [230].

4.1. Epigenetic Modification

On the other hand, epigenetic modification played a great role to induce the silent genes related to bioactive molecules, which are actively produced under symbiotic interactions. Epigenetics refers to the study of DNA sequences that do not changes in mutation but change in gene function [231]. The epigenetic regulations such as methylation, demethylation, acetylation, deacetylation and phosphorylation of histones also regulate the transcription of biosynthetic genes of fungi and are helpful in silencing or expression of such genes related to the production of secondary metabolites [232]. The importance of epigenetic regulation in secondary metabolite production by fungi has been shown in a few reports published [231,233,234,235,236]. Modification or alteration in DNA or chromatin changes the expression level of the selected genes, which directly impacted the biosynthesis of the metabolites in the strain.

4.2. The Co-Culture Strategy

The co-culture is another method to induce the silent biosynthetic gene clusters by interspecies cross-talking of microorganisms. In this method, various combinations of inducers with producer microbial strains are screened for the production of novel molecules. In co-culture technique real-time bioactivity screening can also be measured by the growth of pathogen as co-culture [218]. Recently, Kim et al. [237] reviewed the co-culture interactions of fungi with various actinomycetes for induction of silent biosynthetic gene clusters and reported upregulation and production of novel antibiotics and bioactive compounds. Co-culturing of microbes provides the habitat type environment to producers and helps to promote silent BGCs by producing signal molecules. Exchange of chemical signals of growing organisms is helpful in the induction of defense molecules and other silent BGC, and usually results in the production of new natural products or secondary metabolites in the culture [238].

Another concept has also been introduced to elicit the production of silent secondary metabolites by scaffold technique. In this technique, two types of scaffold named cotton and talc powder are introduced in the medium which physically interacts with the grown culture and elicit chemical signaling of the culture and activate the production of silent BGC. The addition of scaffold in the medium supports the grown culture in formation of biofilm and provides a mimic architecture of natural habitat [239,240]. The addition of scaffold in medium affects the morphology of growing culture and sporulation pattern like an agglomeration of spores, oxygen diffusion in comparison to non-scaffold containing medium and then facilitates more metabolites production [241].

4.3. OSMAC

In the OSMAC technique different cultivation approaches are applied to induce silent bioactive gene clusters to promote more production of secondary metabolites including media variations, variation in media composition, co-cultivation with other strains and variations in cultivations strategy [222,242]. Variation in growth conditions also supports the induction of silent biosynthetic gene clusters and the production of novel compounds. Scherlach and Hertweck [243] and Scherlach et al. [244] reported the production of novel aspoquinolone and aspernidine alkaloid compounds from Aspergillus nidulans by variation in growth conditions.

5. Conclusions

Increasing resistance among microbial pathogens against existing antibiotics has been a major concern during the past several decades. Scientists are exploring new sources of novel antibiotics and other bioactive compounds that can curb pathogenic infections and overcome antimicrobial resistance. Endophytic fungi have been reported to secrete a wide spectrum of bioactive compounds to counter pathogens. In the current review, we have reported 453 new bioactive compounds, including volatile compounds, isolated during the period of 2015-21 from various endophytic fungi belonging to the Ascomycetes, Basidiomycetes, and Zygomycetes classes. Newly reported bioactive compounds have shown activity against various pathogenic bacteria and shown scaffold similarity with alkaloids, benzopyranones, chinones, cytochalasins, mullein, peptides, phenols, quinones, flavonoids, steroids, terpenoids, sesquiterpene, tetralones, xanthones, and others. The lowest in vitro activity in terms of minimum inhibitory concentrations (MICs) in the 0.1–1 µg/mL range against various pathogens was reported for the compounds vochysiamides A (23) and B (24), colletotrichone A (376), 15-hydroxy-1,4,5,6-tetra-epi-koninginin G (322), trichocadinin G (330) and eupenicinicol D (435). Compounds like fusarubin (287), chetomin (62), chaetocochin C (63), and dethiotetra(methylthio)chetomin (64), pretrichodermamide A (296), terpestacin (105), fusaproliferin (106), mutolide (108), isoeugenitol (120) and nigrosporone B (417) were reported to have significant in vitro anti-mycobacterial activity and could be developed as potential drugs against resistant mycobacterial infections. The production of such bioactive compounds and their activity is also affected by the surrounding environment and conditions. Various techniques related to induction of silent gene clusters such as epigenetic modifications, co-culture, OSMAC and mutation have been reported

In most of cases only in vitro data against a limited number of bacteria is reported and there is a great need for extensive in vitro studies including their mode of action, kill curve studies, mutation induction frequency, resistance occurrence frequency studies, in vitro cytotoxicity and initial in vivo evaluation followed by formulation studies. Moreover, there is also a need to perform extensive in vitro efficacy testing studies using panels of references strains and clinical strains to establish MIC₉₀ and MIC₅₀ values. Generation of comparative efficacy data with benchmark clinical compounds is very important from a further development perspective. These extensive studies also help to generate data for understanding the scope of work when we consider such potent molecules for semisynthetic work. The exact studies to be performed during screening and further shortlisting of semi-synthetic molecules can be extracted from this initial extensive work.

Still, more research is required to investigate a new generation of antibiotics which can control the increasing resistance of infectious microorganisms in a sustainable manner. The success of this exploration depends upon screening more and more endophytic fungi and ways of their isolation, fermentation and scale-up.