Next Article in Journal
Selenium Biofortification of Crop Food by Beneficial Microorganisms
Previous Article in Journal
Loss of Kex2 Affects the Candida albicans Cell Wall and Interaction with Innate Immune Cells
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JoF
Volume 6
Issue 2
10.3390/jof6020058
jof-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Patents on Endophytic Fungi Related to Secondary Metabolites and Biotransformation Applications

by
Daniel Torres-Mendoza
1,2,
Humberto E. Ortega
1,3 and
Luis Cubilla-Rios
1,*
1
Laboratory of Tropical Bioorganic Chemistry, Faculty of Natural, Exact Sciences and Technology, University of Panama, Panama 0824, Panama
2
Vicerrectoría de Investigación y Postgrado, University of Panama, Panama 0824, Panama
3
Department of Organic Chemistry, Faculty of Natural, Exact Sciences and Technology, University of Panama, Panama 0824, Panama
*
Author to whom correspondence should be addressed.
J. Fungi 2020, 6(2), 58; https://doi.org/10.3390/jof6020058
Submission received: 31 March 2020 / Revised: 27 April 2020 / Accepted: 29 April 2020 / Published: 1 May 2020
Browse Figures
Versions Notes

Abstract

:
Endophytic fungi are an important group of microorganisms and one of the least studied. They enhance their host’s resistance against abiotic stress, disease, insects, pathogens and mammalian herbivores by producing secondary metabolites with a wide spectrum of biological activity. Therefore, they could be an alternative source of secondary metabolites for applications in medicine, pharmacy and agriculture. In this review, we analyzed patents related to the production of secondary metabolites and biotransformation processes through endophytic fungi and their fields of application. We examined 245 patents (224 related to secondary metabolite production and 21 for biotransformation). The most patented fungi in the development of these applications belong to the Aspergillus, Fusarium, Trichoderma, Penicillium, and Phomopsis genera and cover uses in the biomedicine, agriculture, food, and biotechnology industries.

Graphical Abstract

1. Introduction

The term endophyte refers to any organism (bacteria or fungi) that lives in the internal tissues of a host. This endophyte–host association is complex: it is normally driven without causing harm or apparent disease symptoms and provides benefits in survival, fitness, biodiversity, and ecosystem function for both parties by enhancing the response to environmental stress and producing the same or similar compounds that originate in the host [1,2,3]. In particular, fungal endophytes have been the focus of many studies due to their prospective promise in the production of secondary metabolites with pharmacological, agricultural, industrial, or biotechnological applications [4,5,6].
Endophytic fungi were discovered over a century ago; however, it was not until about three decades ago, with the discovery of the taxol-producing endophytic fungus Taxomyces andreanae, that they gained remarkable relevance due to the abovementioned production of active secondary metabolites [7,8,9,10].
As was the case with taxol, the process for the isolation and purification of metabolites in adequate yields remains a major concern; low yields due to the exploitation of the host for the extraction process of metabolites are also associated with environmental impacts, and new strategies such as involving the use of endophytic microorganisms instead of the host themselves have offered new niches that should be meticulously investigated and used as a base for sustainable research and development [11,12].
The present review covers patents related to the production of natural products with biomedical and agricultural applications using endophytic fungi, enabling the development of new lead compounds in the process of finding new drug candidates or precursors for the synthesis of new molecules. We also cover the production of secondary metabolites in biotransformation processes by using endophytic fungi.

2. Materials and Methods

This review was conducted mainly through searches of the databases Scifinder® and Google Patents. Our search was made under the subjects “endophytic fungi” and “patents” covering the period from 2001 to 2019. 4670 references were found. After removing duplicates, we selected those related to the production of secondary metabolites and biotransformation. Resulting in 245 documents from which 224 were related to any kind of secondary metabolite derived from endophytic fungi and 21 detail biotransformation processes of metabolites through endophytic fungi. The patents covered in this study are described in Table 1 and Table 2.

3. Results

The description and analysis of patents was divided into two sections: those that are connected to the production of secondary metabolites and those associated with biotransformation processes. Likewise, two tables were constructed in which the main generalities of each patent are summarized.

3.1. Production of Secondary Metabolites

Early patents consisted mainly of registering the endophytic strains capable of producing specific compounds or those that represented a novel source of active metabolites (chanoclavine in EP1142986A2; resveratrol in CN1948459A; gallic acid in CN101280279A; taxol in CN101486974A) and very few applications. However, over time, patents were developed to include the registration of methods and procedures to produce and recover the compounds of interest (with a known biomedical application) or to optimize or increase their production (podophyllotoxin in US20040248265A1; taxol in CN1624103A; camptothecin in US20060134762A1; huperzine A in CN101275116A). In the last ten years, patents have been focused on using novel or enhanced fermentation processes to obtain high yields of products and provide possible applications for the metabolites (alpha-pyrone in CN110563740A; epimedins A–C in CN110511876A; differanisole A in CN109971655A; 5, 8-ergosterol epoxide in CN109971651A). The distribution of the patents in relation with the principal areas of application are illustrated in Figure 1. The production of taxol and huperzine A were considered as other application outside of their anticancer and anti-Alzheimer property respectively, due to the number of patents and economic importance.
The principal applications consist on providing metabolites that are precursors of bioactive molecules (baccatin III and cephalomannine in CN103194502A) and those that can be use as anticancer, antitumor, antineoplastic or immunosuppressive agents (anthraquinone compounds in CN102586355A; cerrenin D in CN109456191A; alterporriol P in CN102633616A; dalesconol A and B in CN104031948A; quinazoline alkaloid compound in CN103570744A); in pesticides, insecticidal, algal control (diterpene alkaloid-like compounds in CN102190699A); as antibacterial, antibiotic, antimicrobial, bacteriostatic (beauvericin in CN101240249A; diterpene alkaloid compound in CN102190612A); as antifungal and antimycotics (Trichoderma acid in CN103083290A); in neurodegenerative diseases and neuroprotective agent (huperzine A in CN102191294A); as agents in pharmacy, food, cosmetics, agriculture and health care products (pseutorin A in CN104774774A; alterlactone in CN110093383A); antioxidant (flavipin in CN103087923A); anti-inflammatory and anti-rrheumatic (1,4-napthoquinones in CN109293494A); in cardiovascular diseases (breviscapine in CN1421522A); anti-diabetes (2 isabolene sesquiterpenes in CN109096056A); anti-tuberculosis (enniatin compounds in CN101669939A); antiviral (alterporriol Q and R in CN102643186A); as pigments; hepatoprotective agents (pyrrole-type compounds in CN103667073A); in biofuels. Table 1 displays the patents, endophytic fungi, host organism, secondary metabolites, and disclosed applications. The structures of the compounds listed in Table 1 and Table 2 are shown in Figure S1 (see the Supplementary Information).
The principal endophytic fungi reported in this section of patents belong to the genera Aspergillus, Fusarium, Trichoderma, Penicillium, and Phomopsis with 31, 24, 18, 16, and 8 patents, respectively, and compounds such as taxol or paclitaxel, huperzine A, camptothecin, podophyllotoxin, and resveratrol. Methods for enhancing their production represented most of the registered applications. Furthermore, the diversity of compound structures demonstrates the capability of fungi to synthetize simple or very complex molecules.
Mostly, Aspergillus endophytes from plants of the genera Taxus and Torreya are described as having applications related to obtaining the highest yield of paclitaxel or its precursors, like baccatin III and cephalomannine, due to their anticancer activity. Endophytes from Huperzia serrata have been linked to the production of huperzine A and its analogs due to their anti-senile dementia and anti-neurodegenerative applications. Plant endophytes such as Nothapodytes nimmoniana and Camptotheca acuminata have been linked to the production of the antineoplastic agent camptothecin and some analogs. Production of the lignan-type compound podophyllotoxin has been described for several endophytes. This compound has high biomedical potential as an anticancer, antiviral, and antibacterial agent, among others, and is the precursor of the anticancer drugs etoposide and teniposide. The stilbenoid compound found on grape skin, resveratrol, could have promising therapeutic actions against obesity, type II diabetes mellitus, metabolic syndrome, cancer, autism, dementia, and Alzheimer’s disease [13]. Therefore, a number of patents involving endophytes of the genera Cladosporium, Fusarium, Alternaria, and Penicillium for its production were registered. The demand for natural resveratrol has gained traction in various end-use industries.

3.2. Biotransformation by Endophytic Fungi

Biotechnological processes enable the production of useful molecules with a decrease in the generation of pollutants, reducing the use of solvents and reagents, minimizing the consumption of energy, and providing a way to obtain active compounds with greater specificity and efficiency. The use of endophytic fungi in biotechnological processes, such as biotransformation, is in its early stages of development and has some limitations [238]. However, there have been some reports of fungi that have been used in biotransformation [239,240,241,242].
Table 2 lists a group of patents that illustrate the efforts toward using endophytic fungi to obtain molecules of biological importance such as the ginsenosides [243] and glycyrrhetinic acid monoglucuronide [244].
Fungi from the genera Absidia, Zygorhynchus, Xylaria, and Fusarium have been patented to obtain ginsenoside Rd by the transformation of ginsenoside Rb1. Fungi from the genera Microsphaeropsis, Aspergillus, and Chaetomium have been patented for the biotransformation of glycyrrhizinic acid into glycyrrhetinic acid monoglucuronide.

4. Discussion

The study of endophytic fungi as a source of bioactive secondary metabolites has its first beginnings in 1993 with the discovery of taxol [4], until then, the primary sources of active natural molecules were isolated mainly from plants [266]. About two decades ago, the study of endophytic fungi as producers of active molecules has been emphasized due to obtaining compounds originally produced by plants or due to the production of novel secondary metabolites [11,267], Thus, fungi from genus Aspergillus, Fusarium, Penicillium and Pestalotiopsis has been recognized as producers of anticancer compounds and having pharmaceutical potential [12,268]. It is estimated that only around 1% of the microorganisms have been cultivated, and within this groups, endophytic fungi corresponded to the least studied [269].
Through this review, we have demonstrated the wide number of endophytic fungi involved in the development of methods and techniques for the application of isolation and fermentation to obtain secondary metabolites with high potential and applications in biomedicine, agriculture, and biotechnology processes. Figure 2 shows the number of patents registered for secondary metabolites and biotransformation processes through endophytic fungi for the period from 2001 to 2019. We found 224 patents related to secondary metabolites and 21 patents related to biotransformation. Aspergillus, Fusarium, Trichoderma, Penicillium, and Phomopsis were the most representative genera for secondary metabolites.
Fusarium and Penicillium were the most commonly registered endophytic fungi genera among the 21 patents reviewed for biotransformation processes. Figure 3 shows the number of patented genera. The most notable applications patented were antimicrobial, antibacterial, anticancer, and those related to neurodegenerative diseases. For biotransformation processes, the conversion of ginsenosides and glycyrrhizinic acid were the most patentable applications due to their importance and potential in the pharmaceutical and food industries.
Table 1 and Table 2 showed that the majority of the endophytic fungi were derived from plants, but we could also find patents where the host was soft corals or insects.
The global market for compounds like taxol is expected to reach USD $99 million by 2021 [270], and for resveratrol, the projected growth from 2018 to 2028 in revenue terms is 8.1% from USD $97.7 million [271]. Under the objectives of the 1992 Convention on Biological Diversity for the sustainable use of its components and the Nagoya Protocol on Access to Genetic Resources and the Fair and Equative sharing of benefits derived from the use of genetic resources [272], endophytic fungi and their derived compounds could open a new set of industries and economics in development countries with high biodiversity for the low-cost yield of high-profit molecules that can be applied in the fields discussed in this review.

Supplementary Materials

The following are available online at https://www.mdpi.com/2309-608X/6/2/58/s1, Figure S1: Structures of the secondary metabolites listed in Table 1 and Table 2.

Author Contributions

D.T.-M. and H.E.O. Performed the data search and analysis, visualized and wrote the manuscript, L.C.-R. conceptualized, visualized, supervised, wrote and review the manuscript. All authors read and approved the final manuscript.

Funding

This project was supported by the National System of Research (SNI) and the National Secretariat for Science and Technology of Panama (SENACYT).

Acknowledgments

The authors want to thank University of Sao Paulo, Brazil, for granted access to “Portal de Periodicos CAPES/MEC” and to Phyllis D. Coley for critical review of the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

  1. Wani, Z.A.; Ashraf, N.; Mohiuddin, T.; Riyaz-Ul-Hassan, S. Plant-endophyte symbiosis, an ecological perspective. Appl. Microbiol. Biotechnol. 2015, 99, 2955–2965. [Google Scholar] [CrossRef] [PubMed]
  2. Zeilinger, S.; Gupta, V.K.; Dahms, T.E.S.; Silva, R.N.; Singh, H.B.; Upadhyay, R.S.; Gomes, E.V.; Tsui, C.K.M.; Chandra Nayak, S. Friends or foes? Emerging insights from fungal interactions with plants. FEMS Microbiol. Rev. 2016, 40, 182–207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Yan, L.; Zhu, J.; Zhao, X.; Shi, J.; Jiang, C.; Shao, D. Beneficial effects of endophytic fungi colonization on plants. Appl. Microbiol. Biotechnol. 2019, 103, 3327–3340. [Google Scholar] [CrossRef] [PubMed]
  4. Newman, D.J.; Cragg, G.M. Endophytic and epiphytic microbes as “sources” of bioactive agents. Front. Chem. 2015, 3, 1–13. [Google Scholar] [CrossRef] [PubMed]
  5. Nisa, H.; Kamili, A.N.; Nawchoo, I.A.; Shafi, S.; Shameem, N.; Bandh, S.A. Fungal endophytes as prolific source of phytochemicals and other bioactive natural products: A review. Microb. Pathog. 2015, 82, 50–59. [Google Scholar] [CrossRef]
  6. Savi, D.C.; Aluizio, R.; Glienke, C. Brazilian plants: An unexplored source of endophytes as producers of active metabolites. Planta Med. 2019, 85, 619–636. [Google Scholar] [CrossRef] [Green Version]
  7. Radić, N.; Štrukelj, B. Endophytic fungi—The treasure chest of antibacterial substances. Phytomedicine 2012, 19, 1270–1284. [Google Scholar] [CrossRef]
  8. Zhang, Y.; Han, T.; Ming, Q.; Wu, L.; Rahman, K.; Qin, L. Alkaloids produced by endophytic fungi: A review. Nat. Prod. Commun. 2012, 7, 963–968. [Google Scholar] [CrossRef] [Green Version]
  9. Zhi-Lin, Y.; Yi-Cun, C.; Bai-Ge, X.; Chu-Long, Z. Current perspectives on the volatile-producing fungal endophytes. Crit. Rev. Biotechnol. 2012, 32, 363–373. [Google Scholar] [CrossRef]
  10. Savidov, N.; Gloriozova, T.A.; Poroikov, V.V.; Dembitsky, V.M. Highly oxygenated isoprenoid lipids derived from fungi and fungal endophytes: Origin and biological activities. Steroids 2018, 140, 114–124. [Google Scholar] [CrossRef]
  11. Venugopalan, A.; Srivastava, S. Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol. Adv. 2015, 33, 873–887. [Google Scholar] [CrossRef] [PubMed]
  12. Gupta, S.; Chaturvedi, P.; Kulkarni, M.G.; Van Staden, J. A critical review on exploiting the pharmaceutical potential of plant endophytic fungi. Biotechnol. Adv. 2020, 39, 107462. [Google Scholar] [CrossRef] [PubMed]
  13. Repossi, G.; Das, U.N.; Eynard, A.R. Molecular basis of the beneficial actions of resveratrol. Arch. Med. Res. 2020. [Google Scholar] [CrossRef] [PubMed]
  14. Imada, T.; Hiruma, N.; Kurihara, Y.; Shinozaki, S.; Miho, S.; Junya, M. Chanoclavine-Producing Endophytic Fungi of the Genus Neotyphodium, and Artificially Endophyte-Infected Plants. EP Patent 1142986 A2, 10 October 2001. [Google Scholar]
  15. Strobel, G.; Stierle, A.A.; Stierle, D.B. Taxol Production by a Microbe. U.S. Patent 6329193 B1, 11 December 2001. [Google Scholar]
  16. Chen, Y.; Yang, L.; Li, S.; Li, Z.; Zhou, B.; Zhang, Q. Erigeron Breviscapus-Endogenic Fungus. CN Patent 1421522 A, 4 June 2003. [Google Scholar]
  17. Hoffman, A. Method for Isolating Taxane Producing Endophytic Fungi from Angiosperms. U.S. Patent 6638742 B1, 28 October 2003. [Google Scholar]
  18. Strobel, G.A. A Cyclic Lipopeptide from Cryptosporiopsis Quercina Possessing Antifungal Activity. U.S. Patent 6613738 B1, 2 September 2003. [Google Scholar]
  19. Strobel, G.A.; Daisy, B. Naphthalene Insect Repellent from Muscodor Vitigenus. U.S. Patent 20040185031 A1, 23 September 2004. [Google Scholar]
  20. Strobel, G.A.; Ezra, D. Application of Volatile Antibiotics and Non-Volatile Inhibitors from Muscodor Spp. to Control Harmful Microbes in Human and Animal Wastes. U.S. Patent 20040206697 A1, 21 October 2004. [Google Scholar]
  21. Porter, J.R.; Eyberger, A.L. Production of Podophyllotoxin by Endophytic Fungi. U.S. Patent 20040248265 A1, 9 December 2004. [Google Scholar]
  22. Tapper, B.A.; Cooper, B.M.; Easton, H.S.; Fletcher, L.R.; Hume, D.E.; Lane, G.A.; Latch, G.C.M.; Pennell, C.G.L.; Popay, A.J.; Christensen, M.J. Improvements in Grass Endophytes. WO Patent 2004106487 A2, 9 December 2004. [Google Scholar]
  23. Tan, F.; Hu, K.; Zhu, S.; Tang, K.; Liao, Z. Method for Increasing Taxol Productivity in Fermentation of Endophytic Fungi from Taxus. CN Patent 1624103 A, 8 June 2005. [Google Scholar]
  24. Strobel, G.A.; Ezra, D. Application of Volatile Antibiotics and Non-Volatile Inhibitors from Muscodor Spp. to Control Harmful Microbes in Human and Animal Wastes. U.S. Patent 6911338 B2, 28 June 2005. [Google Scholar]
  25. She, Z.; Lin, Y.; Xia, X.; Fu, L.; Liang, Y. Manufacture of Red Quinone Compound from Halorosellinia for Application in Antitumor Drugs. CN Patent 1850765 A, 25 October 2006. [Google Scholar]
  26. Puri, S.C.; Verma, V.; Amna, T.; Handa, G.; Gupta, V.; Verma, N.; Khajuria, R.K.; Saxena, A.K.; Qazi, G.N.; Spiteller, M. Novel Endophytic Camptothecin and Camptothecinoid Producing Fungi and Process of Producing the Same. U.S. Patent 20060134762 A1, 22 June 2006. [Google Scholar]
  27. Strobel, G.A.; Ezra, D. Application of Volatile Antibiotics and Non-Volatile Inhibitors from Muscodor Spp. to Control Harmful Microbes in Human and Animal Wastes. U.S. Patent 7070985 B2, 4 July 2006. [Google Scholar]
  28. Jiang, J.; Feng, Y.; Chen, F.; Fang, D.; Cao, X.; Liu, M.; Sun, Y. Manufacture and Application of Plasmin from Ginkgo Biloba Endophytic Fusarium. CN Patent 1896232 A, 17 January 2007. [Google Scholar]
  29. Lin, Z.; Wang, X.; Hu, Y.; Liu, S. Genetically Engineered Cladosporium Caulis with Increased Stilbene Synthase Activity for Manufacture of Resveratrol. CN Patent 1948459 A, 18 April 2007. [Google Scholar]
  30. Xia, G.; Chen, Y.; Zhang, Y.; Wang, X.; Chen, X.; Zhu, J.; Li, B. Manufacture of 2,3-Diamino-6-Hydroxy-Benzoic Acid-2-Ethyl-Hexyl Ester as Antifungal Drug. CN Patent 1951907 A, 25 April 2007. [Google Scholar]
  31. Yu, X.; Shentu, X. Trichoderma Harzianum Rifai Strain l (Cgmcc No.1780) Grown in Ilex Cornuta (Gougu). CN Patent 101037656 A, 19 September 2007. [Google Scholar]
  32. Yu, X.; Shen, T.; Chen, L. Method for Preparing Sesquiterpene Compound Trichothec-9-En-4-Ol,12,13-Epoxy-,Acetate,(4β)-(8CI,9CI) from Trichoderma Harzianum. CN Patent 101041840 A, 26 September 2007. [Google Scholar]
  33. Strobel, G.; Ford, E.; Harper, J.K. Pestalotiopsis Microspora Isolates and Compounds Derived Therefrom. U.S. Patent 7192939 B2, 20 March 2007. [Google Scholar]
  34. Li, W.; Hu, Z.; Zhou, J.; Wang, Z. Acremonium Endophytium Grown in Huperzia Serrata (Sezushan) and Its Application in Producing Huperzine A Analogs. CN Patent 101195804 A, 11 June 2008. [Google Scholar]
  35. Shen, Y.; Du, X.; Lu, C.; Huang, Y.; Zheng, Z.; Su, W. Method for Preparing Biphenyl Compounds with Antitumor and Antioxidation Effects. CN Patent 101234951 A, 6 August 2008. [Google Scholar]
  36. Hong, Y.; Liu, Z.; Xiao, L. Mixed Endophyte Separated from Lycopodium Serratum (Qiancengta), and Method for Preparing Huperzine A from the Endophyte. CN Patent 101275116 A, 1 October 2008. [Google Scholar]
  37. Zhou, L.; Jiang, W.; Peng, Y.; Wang, M.; Xu, L.; Huang, Y.; Zhao, J. Beauvericin-Producing Dioscorea Zingiberensis Endophytic Fusarium Sp. and Its Antibacterial Activity. CN Patent 101240249 A, 13 August 2008. [Google Scholar]
  38. Zhan, Y.; Qi, F.; Jing, T.; Zeng, F.; Fan, G.; You, X. Phomopsis Strain for Producing Gallic Acid. CN Patent 101280279 A, 8 October 2008. [Google Scholar]
  39. Strobel, G.A.; Ezra, D. Application of Volatile Antibiotics and Non-Volatile Inhibitors from Muscodor Spp. to Control Harmful Microbes in Human and Animal Wastes. U.S. Patent 7341862 B2, 11 March 2008. [Google Scholar]
  40. Zhou, L.; Wang, J.; Ma, Z.; Li, X.; Huang, Y.; Wang, M.; Zhao, J. Paris Polyphylla Endophytic Fusarium Sp. Capable of Generating Antibacterial Active Components. CN Patent 101412971 A, 22 April 2009. [Google Scholar]
  41. Wu, S.; Chen, Y.; Li, Z.; Yang, L.; Li, S. Phomoposolide Compound with Some Inhibitory Action on Phytopathogenic Fungi. CN Patent 101468977 A, 1 July 2009. [Google Scholar]
  42. Wu, S.; Chen, Y.; Li, Z.; Yang, L.; Li, S. 7α-Acetoxy-Multiplolide A and Its Application to Preparation of Antimicrobial Drug. CN Patent 101468996 A, 1 July 2009. [Google Scholar]
  43. Gao, J.; Qin, J.; Zhang, Y.; Zhang, A. Compound Separated from Ethyl Acetate Extract of Fermented Solution of Chaetomium Globosum. CN Patent 101481379 A, 15 July 2009. [Google Scholar]
  44. Zhao, K.; Zhou, D.; Ping, W.; Li, Q. An Endophytic Fungus Aspergillus Niger Var. Taxi HD86-9 Producing Paclitaxel. CN Patent 101486974 A, 22 July 2009. [Google Scholar]
  45. Zhao, B.; Lai, H.; Ma, Y.; He, W.; Liu, B. Method for Separating Endogenous Fungi Producing Spherosin. CN Patent 101503658 A, 12 August 2009. [Google Scholar]
  46. Wu, B.; Wu, L.; Chen, D.; Xia, Y.; Ge, M.; Luo, M.; Yin, Y.; Yang, Z.; Yang, T.; Jin, W. Preparation of Fibrinolysin from Fusarium and Its Use as Thrombolytic Drugs. CN Patent 101525611 A, 9 September 2009. [Google Scholar]
  47. Zhang, P.; Yu, L.; Zhou, P. Method for Manufacturing Paclitaxel with Endophytic Fungus Aspergillus Candidus HUST-RBB3. CN Patent 101586082 A, 25 November 2009. [Google Scholar]
  48. Strobel, G. Gliocladium Isolate C-13 and Methods of Its Use for Producing Volatile Compounds and Hydrocarbons. U.S. Patent 20090142816 A1, 4 June 2009. [Google Scholar]
  49. Chen, S.; Huang, C.; Zhang, C.; Lin, F. Application of Chaetomium Cupreum Strain in Antitumor Areas. CN Patent 101619291 A, 6 January 2010. [Google Scholar]
  50. Lai, X.; Wang, J.; Lin, Y.; She, Z.; Chen, Y. Medical Application of Enniatin Compounds for Treating Drug-Resistant Mycobacterium Avium-Intracellulare Infection. CN Patent 101669939 A, 17 March 2010. [Google Scholar]
  51. Zhou, X.; Zhang, Y.; Yu, C.; Kang, L.; Sun, X.; Zou, W. Method for Enhancing Yield of Antitumor Anthraquinone-like Compounds from Fusarium Proliferatum by Adaption of Various Inoculation Methods. CN Patent 101701230 A, 5 May 2010. [Google Scholar]
  52. Hou, C.; Li, X. High-Yield Hypocrellin-Producing Shiraia Bambusicola Strain ZZZ-817 and Its Application in Producing Hypocrellin by Fermentation. CN Patent 101875905 A, 3 November 2010. [Google Scholar]
  53. Hong, Y.; Liu, D.; Cheng, P.; Liu, Z.; Xiao, L. Huperzine A-Producing Endophyte TCM-01 Strain. CN Patent 101914452 A, 15 December 2010. [Google Scholar]
  54. Lee, I.J.; Muhammed, H.; Hwang, Y.H.; Shin, D.H.; Na, C.I. Gibberellin Production Using Soybean Endophyte Scolecobasidium Tshawytschae P-4-3. KR Patent 2010104252 A, 29 September 2010. [Google Scholar]
  55. Blunt, J.; Cole, T.; Munro, M.; Sun, L.; Weber, J.-F.R.; Ramasamy, K.; Abu Bakar, H.; Abdul Majeed, A.B.B. Bioactive Compounds Derived from Endophytic Aspergillus Fungus Strain Isolated from Garcinia Scortechinii. WO Patent 2010062159 A1, 3 June 2010. [Google Scholar]
  56. Zhu, D.; Zhang, Z.; Zeng, Q.; Yan, M.; Wang, J. Huperzine A-Producing Huperzia Serrata Endophytic Shiraia Strain. CN Patent 101942393 A, 12 January 2011. [Google Scholar]
  57. Zhang, Y. Induction of Nothapodytes Nimmoniana Endophyte to Produce Sugar Derivative of Camptothecin. CN Patent 102080110 A, 1 June 2011. [Google Scholar]
  58. Zhang, Y. Method for Inducing Nothapodytes Nimmoniana Endophyte to Produce 10-Hydroxy Camptothecin. CN Patent 102080111 A, 1 June 2011. [Google Scholar]
  59. Zhang, Y. Induction of Nothapodytes Nimmoniana Endophyte to Manufacture 9-Methoxycamptothecin. CN Patent 102080112 A, 1 June 2011. [Google Scholar]
  60. Wang, G.; Zhang, C.; Lin, F.; Xia, J.; Zhou, Z. Endophytic Fungus Phomopsis Wenchengensis ZJWCF252 for Manufacture of Agricultural Fungicide 2,3-Dihydro-2-Hydroxy-2,4-Dimethyl-5-Trans-Propenylfuran-3-One. CN Patent 102154116 A, 17 August 2011. [Google Scholar]
  61. Yu, L.; Shi, Y.; Liu, Z.; Huang, J.; Hu, W. Fermentation Method for Manufacturing Huperzine A with Colletotrichum Gloeosporioides YLJ-13. CN Patent 102168017 A, 31 August 2011. [Google Scholar]
  62. Ji, N.; Qiao, M. Application of Diterpene Alkaloids, Secondary Metabolite of Alga Endophytic Fungi, as Insecticide. CN Patent 102187870 A, 21 September 2011. [Google Scholar]
  63. Ji, N.; Qiao, M. Diterpene Alkaloid Compound from Natural Algae Endophytic Fungus and Preparation and Application Thereof. CN Patent 102190612 A, 21 September 2011. [Google Scholar]
  64. Ji, N.; Qiao, M. Agricultural Application of Diterpenoid Alkaloid of Endophytic Fungi of Algae. CN Patent 102190614 A, 21 September 2011. [Google Scholar]
  65. Ji, N.; Qiao, M. Manufacture of Insecticidal Diterpene Alkaloid from Endophytic Fungus Aspergillus Oryzae. CN Patent 102190698 A, 21 September 2011. [Google Scholar]
  66. Lan, S.; Xiao, H.; Wang, L. Method for Manufacture of Huperzine A with Endophytic Fungus by Fermentation. CN Patent 102191294 A, 21 September 2011. [Google Scholar]
  67. Ji, N.; Qiao, M. A Diterpene Alkaloid-like Compound of Endophytic Fungus of Marine Algae, and Its Preparation and Application as Insecticide. CN Patent 102190699 A, 21 September 2011. [Google Scholar]
  68. Zheng, C.; Sun, T.; Bai, C.; Sun, Y.; Tan, J. Verticillium Dahliae for Producing Glycyrrhetinic Acid. CN Patent 102220247 A, 19 October 2011. [Google Scholar]
  69. Bora, T.C.; Mazumder, S.; Gogoi, B.K.; Rao, P.G.; Mondhe, D.M.; Saxena, A.K. Antimicrobial and Anti-Cancer Lactone Metabolite from Aspergillus Elegans, Growing in Asparagus Racemosus, Willd, and the Process for Production Thereof. IN Patent 2010DE00131 A, 9 December 2011. [Google Scholar]
  70. Shibuya, H.; Ohashi, K.; Nakoshi, T. Colorless Antioxidant Neohexahydrocurcumin and Its Manufacture with Diaporthe. JP Patent 2011051953 A, 17 March 2011. [Google Scholar]
  71. Strobel, G.A.; Tomsheck, A.R. Volatile Organic Compound Production by Endophytic Fungi Isolated from Persea Indica. WO Patent 2011146634 A1, 24 November 2011. [Google Scholar]
  72. Miller, J.D.; Adams, G.W.; Sumarah, M. Antifungal Metabolites from Fungal Endophytes of Pinus Strobus. CA Patent 2766412 A1, 28 July 2012. [Google Scholar]
  73. Feng, L.; Song, P.; Hong, W.; Wu, C.; Zhu, L. Penicillium Steckii for Manufacture of Triptolide. CN Patent 102321545 A, 18 January 2012. [Google Scholar]
  74. Chen, H.; Wang, Y. Screening of New Camptothecin-Producing Fungus for Manufacture of Camptothecin. CN Patent 102417883 A, 18 April 2012. [Google Scholar]
  75. Zheng, C.; Sun, P.; Han, T.; Ma, W.; Sun, H. Trichodermanin b in Secondary Metabolites of Cephalotaxus Fortunei Endogenous Fungi, Its Preparation Method and Application to Prepare Antifungal, Antiviral and Antitumor Drugs. CN Patent 102464634 A, 23 May 2012. [Google Scholar]
  76. Zhao, C.; Zhu, Y.; Liang, Z.; Zhang, J.; Qian, Z. One Endophytic Fungi from Sinopodophyllum Emodi and the Application Thereof. CN Patent 102559517 A, 11 July 2012. [Google Scholar]
  77. Zhou, X.; Zhou, W.; Cai, M.; Zhang, Y. Culture Medium and Method for Producing Anticancer Anthraquinone-like Compounds with Marine Mangrove Endophytic Fungus. CN Patent 102586355 A, 18 July 2012. [Google Scholar]
  78. Zheng, C.; Liu, Y.; Lu, X. Endophytic Fungi for Improving Main Active Ingredient Contents of Schisandra Chinensis by Fermentation. CN Patent 102628018 A, 8 August 2012. [Google Scholar]
  79. Wang, C.; Shao, C.; Zheng, C. Anthraquinone Dimer Derivative Alterporriol P with Antitumor Activity and Its Preparation and Application. CN Patent 102633616 A, 15 August 2012. [Google Scholar]
  80. Ji, N.; Liu, X.; Miao, F. Sesquiterpenoid Compound, Albican-11,14-Diol, in Endophytic Fungus of Algae, Aspergillus Versicolor, and Its Fermentation Preparation and Application as Antibacterial Agents and Insecticides. CN Patent 102643167 A, 22 August 2012. [Google Scholar]
  81. Wang, C.; Shao, C.; Zheng, C. Two Anthraquinone Dimer Derivatives, Their Preparation Method and Application in Preparing Antiviral Drugs. CN Patent 102643186 A, 22 August 2012. [Google Scholar]
  82. Zheng, C.; Sun, Y.; Bai, C.; Kong, D.; Tan, J. Penicillium Chrysogenum Effectively Increasing Glycyrrhetinic Acid Content of Radix Glycyrrhizae through Fermentation. CN Patent 102643755 A, 22 August 2012. [Google Scholar]
  83. Wang, M.; Xu, X.; Zhao, X.; Shu, S.; Xu, H. No TitleHuperzine A-Producing Endophytic Fungi Colletotrichum Gloeosporioides ES026 of Huperzia Serrata. CN Patent 102653720 A, 5 September 2012. [Google Scholar]
  84. Zheng, C.; Liu, Y.; Lu, X. Endophytic Aspergillus Penicillioides Capable of Increasing Main Active Components of Schisandra Chinensis through Fermentation. CN Patent 102660466 A, 12 September 2012. [Google Scholar]
  85. Zheng, C.; Tan, J.; Bai, C.; Sun, Y.; Kong, D. Endophytic Fusarium Oxysporum of Glycyrrhiza for Generating Glycyrrhetinic Acid. CN Patent 102660467 A, 12 September 2012. [Google Scholar]
  86. Han, T.; Ming, Q.; Qin, L.; Zhang, Q.; Huang, B.; Zhang, H.; Zheng, C.; Huang, F. Endophytic Trichoderma Atroviride of Salvia Miltiorrhiza for Manufacture of Tanshinone I and Tanshinone IIa. CN Patent 102676392 A, 19 September 2012. [Google Scholar]
  87. Ji, N.; Miao, F. Tetracyclic Diterpenoid Compound and Preparation for Biopesticide. CN Patent 102701935 A, 3 October 2012. [Google Scholar]
  88. Li, Q.; Yang, K.; Liang, J.; Kong, X.; Xia, S. Cladosporium Sp. XJ-AC03 for Manufacture of Aconitine. CN Patent 102703327 A, 3 October 2012. [Google Scholar]
  89. Shi, J. Alternaria for Promotion of Resveratrol in Wine Fermentation. CN Patent 102719362 A, 10 October 2012. [Google Scholar]
  90. Zhao, B.; Liu, S.; Su, D.; Lu, W.; Chen, J.; Hu, B.; Liu, T.; Chen, Y.; Liu, Y. Method for Separating Swainsonine-Producing Endophytic Fungi from Oxytropis Glabra. CN Patent 102732427 A, 17 October 2012. [Google Scholar]
  91. Fu, Y.; Zu, Y.; Zhao, J.; Gao, Y.; Luo, M.; Gu, C. Cajaninstilbene Acid-Producing Fusarium Oxysporum, an Endophytic Fungus in Cajanus Cajan. CN Patent 102732428 A, 17 October 2012. [Google Scholar]
  92. Yu, Y. Sophora Alopecuroides Endophytic Fungi for Producing Matrine as Bactericide. CN Patent 102787077 A, 21 November 2012. [Google Scholar]
  93. Lu, Y.; Wang, J. Application of Ceriporia Lacerata DMC1106 for Manufacture of Antitumor 2′,4′-Dihydroxy-6′-Methoxy-3′,5′-Dimethyl Chalcone. CN Patent 102807956 A, 5 December 2012. [Google Scholar]
  94. Deshmukh, S.K.J.R.; Verekar, S.A.; Mishra, P.D.; Eyyammadichiyil, S.S.; Joshi, K.S.; Fiebig, H.-H.; Kelter, G. Dipeptide Derivative for the Treatment of Cancer Produced by an Endophytic Fungus. WO Patent 2012020364 A1, 16 February 2012. [Google Scholar]
  95. Tan, R.; Wei, W.; Jiang, R.; Zhao, G. Libertellenone G Having Inhibition on Acetylcholinesterase, Its Preparation Method and Use for Preparing Drugs for Treating Alzheimer Disease. CN Patent 103073527 A, 1 May 2013. [Google Scholar]
  96. Luo, Y.; Pu, X.; Qu, X.; Chen, F.; Zhang, G. Fermentative Camptothecin Production by Endophytic Trichoderma Viride Strain. CN Patent 103074236 A, 1 May 2013. [Google Scholar]
  97. Li, H.; Li, D.; Zhang, W. Application of Trichodermic Acid in Preparation of Antifungal Drugs. CN Patent 103083290 A, 8 May 2013. [Google Scholar]
  98. Ye, Y.; Xiao, Y.; Li, H.; Li, C.; Liu, J. Chaetomium Globosum, an Endophytic Fungus in Gingko Biloba, for Manufacture of Antioxidant Flavipin. CN Patent 103087923 A, 8 May 2013. [Google Scholar]
  99. Wu, S.; Wang, M.; Liu, H. Huperzia Serrata Endophytic Fungi Colletotrichum for Manufacture of Huperzine A. CN Patent 103103134 A, 15 May 2013. [Google Scholar]
  100. Zhao, K. Manufacture of Paclitaxel and Precursor with Endophytic Fungus HDFS4-26 of Nodulisporium Sylviforme. CN Patent 103194502 A, 10 July 2013. [Google Scholar]
  101. Wang, J.; Song, Y.; Liu, H. Manufacture of Alkaloid with Endophytic Funus of Tripterygium Wilfordii. CN Patent 103288807 A, 11 September 2013. [Google Scholar]
  102. Wu, S.; Chen, Y.; Miao, C. Manufacture of Isopimarane Diterpene Fungicides with Endophytic Fungus of Neem. CN Patent 103360351 A, 23 October 2013. [Google Scholar]
  103. Fan, G.; Wu, C.; Fang, S.; Wang, J.; Li, T.; Xie, N. Endophytic Fungus Colletotrichum of Cyclocarya Paliurus for Manufacture of Red Pigment. CN Patent 103436451 A, 11 December 2013. [Google Scholar]
  104. Reddy, D.S.; Raut, G.N.; Pandrangi, S.S. Antitubercular Diaportheone B Analogs and Synthesis Thereof. IN Patent 2011DE03381 A, 31 May 2013. [Google Scholar]
  105. Strobel, G.A.; Tomsheck, A.R. System and Method of Producing Volatile Organic Compounds from Fungi. U.S. Patent 20130137131 A1, 30 May 2013. [Google Scholar]
  106. Strobel, G.A.; Ren, Y.; Teplow, D.B. Endophytic Fungi from Pteromischum Sp. Plant, Compounds and Methods of Use. U.S. Patent 20130177596 A1, 11 July 2013. [Google Scholar]
  107. Green, W.A.; Strobel, G.A. Compositions of Volatile Organic Compounds and Methods of Use for Treating, Inhibiting or Preventing Plant Pathogenic Disease. U.S. Patent 20130224315 A1, 29 August 2013. [Google Scholar]
  108. Strobel, G.A.; Tomsheck, A.R. Production of Volatile Organic Compounds by Endophytic Fungi. U.S. Patent 20130252289 A1, 26 September 2013. [Google Scholar]
  109. Gandhi, N.R.; Palmer Skebba, V.; Strobel, G.A. Antimicrobial Compositions and Related Methods of Use. U.S. Patent 20130302480 A1, 14 November 2013. [Google Scholar]
  110. Chelliah, J.; Jayeeta, P. Cost-Effective Process for Commercial Production of Paclitaxel by Fusarium Solani. WO Patent 2013164834 A1, 7 November 2013. [Google Scholar]
  111. Shao, C.; Wang, C.; Xu, R. Alkaloid Compound, Its Preparation Method and Application as Tumor Cell Growth Inhibitor. CN Patent 103570744 A, 12 February 2014. [Google Scholar]
  112. Liu, S. Isolation of Resveratrol with High Purity from Polygonum Cuspidatum Fermentation Broth. CN Patent 103627736 A, 12 March 2014. [Google Scholar]
  113. Zhang, Z.; Li, P.; Zhu, D.; Yan, R.; Wang, Y.; Yang, H. Manufacture of Perylenequinone Compounds with Endophytic Fungus Shiraia Sp. Slf-14. CN Patent 103642864 A, 12 March 2014. [Google Scholar]
  114. Dong, L.; Ling, Q. Endophytic Fungi in Huperzia Serrata for Manufacture of Huperzine A. CN Patent 103667070 A, 26 March 2014. [Google Scholar]
  115. Shan, W.; Ying, Y.; Zhan, Z. Endophytic Fungus of Huperzia Serrata for Preparation of 8α,15α-Epoxy Huperzine A. CN Patent 103667072 A, 26 March 2014. [Google Scholar]
  116. Shan, W.; Ying, Y.; Zhan, Z. Endophytic Fungi of Huperzia Serrata and Its Application in Azole Drug for Liver Protection. CN Patent 103667073 A, 26 March 2014. [Google Scholar]
  117. Wu, S.; Zhang, F.; Zheng, Y.; Liu, H. Endophytic Fungi Ceriporia Lacerata MY183 and Hypoxylon Investiens MY311 of Phlegmariurus for Manufacture of Huperzine A. CN Patent 103820331 A, 28 May 2014. [Google Scholar]
  118. Wu, S.; Zheng, Y.; Zhang, F.; Liu, H. Endophytic Fungus of Huperzia Serrata for Manufacture of Huperzine A. CN Patent 103820332 A, 28 May 2014. [Google Scholar]
  119. Liu, M.; Duan, Z.; Lv, Z. High Paclitaxel-Producing Endophytic Fungi Botryosphaeria Dothidea for Manufacture of Paclitaxel. CN Patent 103911293 A, 9 July 2014. [Google Scholar]
  120. Zheng, C.; Jiaojia, C.; Lu, X.; Zhang, P. Schisandra Chinensis Fruit Endophytic Fungi Producing Protocatechualdehyde. CN Patent 103966109 A, 6 August 2014. [Google Scholar]
  121. Lu, Y.; Pan, Z.; Tan, R.; Jiao, R.; Zhao, G. Manufacture of Immunosuppressive Compound with Marine Endophytic Fungi. CN Patent 104031948 A, 10 September 2014. [Google Scholar]
  122. Li, C.; Ding, W. Xanthone Derivative, Its Preparation Method by Fermentation, Extraction and Recrystallization, and Application Thereof in Preparing Microbicide for Controlling Phytopathogenic Fungi. CN Patent 104059044 A, 24 September 2014. [Google Scholar]
  123. Mu, H. Manufacture of Taxol with Endophytic Fungi of Chinese Yew Seed. CN Patent 104073529 A, 1 October 2014. [Google Scholar]
  124. Bai, J.; Pei, Y.; Hua, H.; Li, Z.; Chen, G.; Lv, X. Spiro-Dinaphthyl Compound, Preparation Method and Application. CN Patent 104086522 A, 8 October 2014. [Google Scholar]
  125. Yu, Z.; Li, H.; Nan, X.; Cheng, R. Manufacture of Red Pigment with Ginkgo Leaf Endophyte for Use as Dye. CN Patent 104109691 A, 22 October 2014. [Google Scholar]
  126. Spangenberg, G.C.; Sawbridge, T.I.; Rochfort, S.J.; Mattner, S.W.; Mann, R.C. Fungi and Products Thereof. U.S. Patent 20140082771 A1, 20 March 2014. [Google Scholar]
  127. Niu, M.; Wan, P.; Zhang, T.; Li, X.; Qin, C.; Gong, Q.; Zhang, M.; Sun, J.; Li, X. Forsythia Suspensa Endogenetic Fungus for Producing Forsythoside A, B and Phillyrin as Antibacterial Substances. CN Patent 104293678 A, 21 January 2015. [Google Scholar]
  128. Zheng, C.; Zhang, P.; Kong, D.; Zhai, L. Manufacture of Glycyrrhetinic Acid with Endophytic Fungus. CN Patent 104357525 A, 18 February 2015. [Google Scholar]
  129. Qi, H.; Shi, Y.; Wang, X. Method for Separating and Screening Endophytic Fungi of Gardenia Jasminoides. CN Patent 104450528 A, 25 March 2015. [Google Scholar]
  130. Wu, W.; Pan, F.; Su, X.; Wang, N.; Cai, S.; Hou, K. No TitleFusarium Tricinctum CBY4 as Fritillaria Cirrhosa Endophytic Fungus and Its Application in Preparing Peimisine and Peiminine. CN Patent 104450531 A, 25 March 2015. [Google Scholar]
  131. Zhang, W.; Zhang, Y.; Tao, M.; Li, H. A Kind of Preparation Method of Agalloch Eaglewood Chromone Constituents via Inoculation of Aquilaria Sinensis Sawdust with Botryosphaeria Rhodina, Solid Fermentation, and Extraction. CN Patent 104593443 A, 6 May 2015. [Google Scholar]
  132. Li, Y.; Zhou, X.; Yang, J.; Jian, Z.; Meng, L. Endophytic Fungi of Taxus for Efficient Manufacture of Baccatin III. CN Patent 104726345 A, 24 June 2015. [Google Scholar]
  133. Feng, Y. Preparation Method of Gastrodin by Symbiotic Fermentation of Gastrodia Endophyte and Armillaria Mellea. CN Patent 104762348 A, 8 July 2015. [Google Scholar]
  134. Zheng, C.; Zhang, P.; Zhai, L.; Xu, H. Endophytic Aspergillus Fumigatus GRP13 Capable of Producing Pseurotin A as Food Preservative. CN Patent 104774774 A, 15 July 2015. [Google Scholar]
  135. Hua, R.; Fu, W.; Lv, P.; Bai, Y.; Wu, X.; Shi, T. Manufacture of Antimicrobial with Spiraea Salicifolia Endophytic Fungus and Isolation of the Antimicrobial. CN Patent 104789613 A, 22 July 2015. [Google Scholar]
  136. Zhao, B.; Yan, S.; Chen, B.; Qian, H.; Huang, X.; Zhu, Y. Plant-Derived Endophytic Fungus for Producing β-Glucosidase, and Application Thereof. CN Patent 104805017 A, 29 July 2015. [Google Scholar]
  137. Pan, H.; Hu, J.; Wang, S. Plant Endophytic Fungus Eupenicillium Brefeldianum F4a for Manufacture of Brefeldin A. CN Patent 104877910 A, 2 September 2015. [Google Scholar]
  138. Guo, B.; Feng, S.; Chen, X.; He, M.; He, W.; Wei, Y. One Kind of Endophytic Mortierella of Huperzia Serrata and Its Application. CN Patent 105039173 A, 11 November 2015. [Google Scholar]
  139. Yang, G.; Dong, F.; Li, P.; Qiu, Y.; Bai, X. Paeonol-Producing Endophytic Fungus of Paeonia and Its Application. CN Patent 105039174 A, 11 November 2015. [Google Scholar]
  140. Yang, G.; Dong, F.; Yang, F.; Qiu, Y.; Bai, X.; Lin, L. Paeonol Producing Peony Endophytic Fungi and Its Application. CN Patent 105039175 A, 11 November 2015. [Google Scholar]
  141. Yang, G.; Meng, L.; Li, P.; Dong, F.; Qiu, Y.; Lin, L. Peony Endophytic Fungi and Its Application. CN Patent 105039176 A, 11 November 2015. [Google Scholar]
  142. Liu, J.; Peng, Y.; Hong, J.; Yin, Z.; Liu, X.; Ren, N. Apocynaceae Endophytic Fungi CH1 Producing Ethyl Vincamine and Application Thereof. CN Patent 105200091 A, 30 December 2015. [Google Scholar]
  143. Gandhi, N.R.; Palmer Skebba, V.; Strobel, G.A. Antimicrobial Compositions and Related Methods of Use. U.S. Patent 20150073048 A1, 12 March 2015. [Google Scholar]
  144. Singh, D.; Sharma, J.P.; Jaglan, S.; Dar, A.H.; Khajuria, A.; Singh, V.P.; Vishwakarma, R.A. Brachiatin D and Process for Production Thereof. WO Patent 2015029069 A1, 5 March 2015. [Google Scholar]
  145. Yang, G.; Li, P.; Dong, F.; Qiu, Y.; Lin, L. Peony Endophytic Fungi and Technique of Producing Paeonol Using It. CN Patent 105238697 A, 13 January 2016. [Google Scholar]
  146. Xiao, J.; Lai, Y.; Li, W.; Bi, Y.; Li, W.; Li, Q.; Ji, B.; Dong, H.; Sun, L.; Bian, S. A Wild Soybean Endophytic Fungi with High Yield of Oleanolic Acid. CN Patent 105238700 A, 13 January 2016. [Google Scholar]
  147. Yang, S.; Fang, R.; Tang, C. Aspergillus Fumigatus Fungus TMS-26 for Producing Taxol. CN Patent 105274005 A, 27 January 2016. [Google Scholar]
  148. Wang, Y.; Fan, M.; Ma, Z.; Hu, F.; Zhang, X.; Tian, C.; Lu, R. A Method for Cultivating and Screening Taxol-Producing Bacteria from Yew. CN Patent 105316238 A, 10 February 2016. [Google Scholar]
  149. Zheng, C.; Qin, L.; Li, X.; Han, T.; Zhang, Q.; Jiang, Y.; Jia, M. Salvia Miltiorrhiza Endophytic Fungi and Application Thereof. CN Patent 105349431 A, 24 February 2016. [Google Scholar]
  150. Cheng, J.; He, L.; Wei, H.; Hu, C.; Fang, R.; Li, H. Method for Improving Paclitaxel Yield in Endophytic Fungi Fermented Product. CN Patent 105400842 A, 16 March 2016. [Google Scholar]
  151. Zheng, C.; Qin, L.; Li, X.; Han, T.; Xin, H.; Zhang, Q.; Jiang, Y. Endophytic Fungi for Producing Ergosterol and Application Thereof. CN Patent 105505798 A, 20 April 2016. [Google Scholar]
  152. Cheng, J.; He, L.; Hu, C.; Wei, H.; Fang, R.; Zou, J.; Li, H. Culture Composition Containing Paclitaxel and the Preparation Method Thereof. CN Patent 105506021 A, 20 April 2016. [Google Scholar]
  153. Han, W.; Li, W.; Han, Z.; Jia, M.; Zhang, H.; Sun, J.; Wu, Y.; Zhou, Y. Mucor Racemosus Nsh-d with Efficient Expression of Huperzine a and Its Application. CN Patent 105670940 A, 15 June 2016. [Google Scholar]
  154. Fu, Y.; Yao, M.; Gao, C.; Sun, J.; Wang, W.; Zhao, C.; Gu, C. A Pigeonpea Endophytic Fungi for High Yielding of Flavipin and Its Application. CN Patent 105838613 A, 10 August 2016. [Google Scholar]
  155. Tang, X.; Wu, X.; Liu, X.; Ma, Y.; Feng, X. Method for Preparing Cytochalasin H from Mangrove Endophytic Fungi. CN Patent 105925646 A, 7 September 2016. [Google Scholar]
  156. Liu, C.; Guo, Z.; Wei, X.; He, H.; Xue, Y.; Zou, K. Endophytic Fungi Paraconiothyrium Brasiliense Used for Preparing Perlolyrine and Preparation Method Thereof. CN Patent 106010980 A, 12 October 2016. [Google Scholar]
  157. Lei, B.; Kang, J.; Wu, X.; Qian, Y.; Wen, T.; Zhou, S. Nothapodytes Pittosporoides Endophyte Trichoderma Strain and Camptothecin Extraction Method Thereof. CN Patent 106047715 A, 26 October 2016. [Google Scholar]
  158. Gonzalez Coloma, A.; Diaz Hernandez, C.E.; Andres Yeves, M.; Fraga Gonzalez, B.M.; Bolanos Gonzalez, P.; Cabrera Perez, R.; Gimenez Marino, C. Fungal Biocidal Products and Their Use for Control of Phytopathogens and Plant Pests. WO Patent 2016034751 A1, 10 March 2016. [Google Scholar]
  159. Zheng, C.; Huang, G.; Chen, G.; Zheng, C.; Zhou, X.; Bai, M.; Liu, Y. Anti-Vibrios Active Compounds Isolation from Bruguiera Sexangula Endophytic Fungi Useful in Treatment Bacterial Infection. CN Patent 106432168 A, 22 February 2017. [Google Scholar]
  160. She, Z.; Liu, Z.; Tan, C.; Chen, S. Marine Fungus Derived Indenone Derivative and Preparation Method and Application Thereof. CN Patent 106434361 A, 22 February 2017. [Google Scholar]
  161. Han, W.; Han, Z.; Li, W.; Jia, M.; Sun, J.; Han, B.; He, J.; Zhou, Y. Fusarium Verticillioides with Huperzine-Producing Function, and Its Use in the Biosynthesis of the Medicine for Treating Alzheimer’s Disease and Vascular Dementia. CN Patent 106497803 A, 15 March 2017. [Google Scholar]
  162. Han, W.; Han, Z.; Li, W.; Jia, M.; Sun, J.; Jia, M.; Yang, M.; Zhou, Y. A Kind of Fermentation Product for Treating Dementia Fungal Strain and Its Application. CN Patent 106497804 A, 15 March 2017. [Google Scholar]
  163. Liu, L.; Chen, B.; Xu, J.; Li, J.; Lin, Y.; Li, M.; Yuan, J. Compound Derived from Tibetan Medicine Endophytic Fungi and Preparation Method and Application Thereof. CN Patent 106588944 A, 26 April 2017. [Google Scholar]
  164. Xu, L. Fermentation and Extraction Method for Azadirachtin. CN Patent 106636247 A, 10 May 2017. [Google Scholar]
  165. Chen, B.; Liu, L.; Jiang, S.; Xu, J.; Xu, A.; Pubu, D.; Li, J. Meconopsis Grandis Endogenetic Fungus DH24 and Application of Producing Pyrrocidines Compounds. CN Patent 106701594 A, 24 May 2017. [Google Scholar]
  166. Xu, L.; Duan, X.; Wei, X.; Xue, J.; Feng, L.; Wu, P. Fungal Tri-Glycolipid Compounds and Application Thereof in Preventing and Treating Fungal Diseases. CN Patent 106946955 A, 14 July 2017. [Google Scholar]
  167. Cao, J.; Tu, Y.; Jin, W. Paclitaxel-Producing Aspergillus Flavus Bp6t2 and Application Thereof. CN Patent 106967622 A, 21 July 2017. [Google Scholar]
  168. Cao, J. Aspergillus Niger Producing Taxane Compound Baccatin III, and Application Thereof. CN Patent 106967623 A, 21 July 2017. [Google Scholar]
  169. Wang, M.; Gao, C.; Wang, Z.; Jie, J.; Han, T.; Xiao, F.; Yang, Q.; Shi, Y. Artemisia Argyi Endophytic Fungus HCH285 Producing Bostrycin. CN Patent 106978356 A, 25 July 2017. [Google Scholar]
  170. Wang, Y.; Ye, R.; Sun, L. Pestalotiopsis Vismiae CAMT 66351 and Application Thereof. CN Patent 107034145 A, 11 August 2017. [Google Scholar]
  171. Qiao, W.; Ling, F.; Xie, Z.; Xia, H.; Ge, X.; Bai, H.; Liu, H.; Wang, T. Highly Effective Paclitaxel-Producing Endophytic Fungi Aspergillus Aculeatus Tax-6 and Its Application. CN Patent 107058118 A, 18 August 2017. [Google Scholar]
  172. Wang, N.; Zhao, Z.; Sun, X.; Chu, Y.; Yao, T.; Liu, Y. Solidago Canadensis Endophytic Fungi Capable of Producing Pectin by Liquid Fermentation and Application Thereof. CN Patent 107118972 A, 1 September 2017. [Google Scholar]
  173. Cao, J.; Jin, W.; Tu, Y. Penicillium Sp. BP6T3 Producing Paclitaxel and Application Thereof. CN Patent 107129936 A, 5 September 2017. [Google Scholar]
  174. Lai, Y.; Zhang, J.; Cui, X.; Xiao, W.; Wang, Y.; Li, Z.; Bu, Y. Method for Improving Scutellarin Content with Microbial Agent. CN Patent 107254504 A, 17 October 2017. [Google Scholar]
  175. Ding, W.; Li, Y.; Li, Y.; Liu, S. Method for Preparing (R)-4-Benzyl-2-Oxazolidinone by Fermentation with Purpureocillium Lilacinum TPL04. CN Patent 107354182 A, 17 November 2017. [Google Scholar]
  176. Mann, R.; Spangenberg, G.C.; Auer, D.; Krill, C.; Sawbridge, T.I.; Edwards, J.; Rochfort, S.J. Novel Endophytic Daldinia Strain Producing Antifungal and Insecticidal Volatile Organic Compounds. WO Patent 2017049353 A1, 30 March 2017. [Google Scholar]
  177. Gonzalez Coloma, A.; Andres Yeves, M.F.; Diaz Hernandez, C.E.; Reina Artiles, M.; Lacret Pimienta, R.; Cabrera Perez, R.; Gimenez Marino, C.; Kaushik, N. Natural Broad-Spectrum Biocides. WO Patent 2017068223 A1, 27 April 2017. [Google Scholar]
  178. She, Z.; Chen, Y.; Yuan, J.; Wang, L.; Liu, Z.; Huang, Y. Ascomycota Sp. CYSK-4 and Application of Ascomylactam Produced by the Same in Preparation of Antineoplastic. CN Patent 107686817 A, 13 February 2018. [Google Scholar]
  179. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope spicata var. prolifera-Endogenous Fusarium and Application to Steroidal Saponin Preparation. CN Patent 107723245 A, 23 February 2018. [Google Scholar]
  180. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope spicata var. prolifera Endogenous Penicillium Oxalicum and Its Application in Preparation of Steroidal Saponin. CN Patent 107723246 A, 23 February 2018. [Google Scholar]
  181. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope spicata var. prolifera-Endogenous Cladosporium and Application to Steroidal Saponin Preparation. CN Patent 107723247 A, 23 February 2018. [Google Scholar]
  182. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope spicata var. prolifera-Endogenous Penicillium and Application to Steroidal Saponin Preparation. CN Patent 107723248 A, 23 February 2018. [Google Scholar]
  183. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope aspicata var. prolifera Endophytic Penicillium and Its Application in Preparation of Steroidal Saponins. CN Patent 107739716 A, 27 February 2018. [Google Scholar]
  184. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope aspicata var. prolifera Endophytic Schizophyllum and Its Application in Preparing Steroidal Saponins. CN Patent 107739717 A, 27 February 2018. [Google Scholar]
  185. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope aspicata var. prolifera Endophytic Aspergillus and Its Application in Preparation of Steroidal Saponins. CN Patent 107739718 A, 27 February 2018. [Google Scholar]
  186. Zhan, Z.; Zhang, C.; Ying, Y.; Shan, W. Plant Endophytic Fungus Bjerkandera Adusta ZJUT-HS8 and Its Application in Preparing 8α,15α-Huperzine A Epoxide. CN Patent 107868757 A, 3 April 2018. [Google Scholar]
  187. Yu, H.; Ye, G.; Pan, W.; Huang, L. Liriope Spicata Endophytic Aspergillus Niger and Application Thereof in Preparing Steroid Saponin. CN Patent 107955793 A, 24 April 2018. [Google Scholar]
  188. Li, J.; Wang, X.; Yu, S.; Li, J. 1-Anilino-2-Pyrrolidone Compound, Its Preparation Method and Application as Antitumor Drug. CN Patent 108264473 A, 10 July 2018. [Google Scholar]
  189. She, Z.; Cui, H.; Pan, Y.; Huang, X.; Liu, H.; Li, C.; Mei, X. Indene Derivative Derived from Diaporthe Sp. SYSU-HQ3, and Application Thereof in Preparation of Anti-Inflammatory Drug. CN Patent 108277164 A, 13 July 2018. [Google Scholar]
  190. Yang, X.; Wang, N.; Kang, Y.; Ma, Y.; Luo, J.; Cao, X.; Xue, L.; Wu, Y. Preparation of the Furanone Derivative and Its Medical Application. CN Patent 108383811 A, 10 August 2018. [Google Scholar]
  191. Ji, N.; Song, Y. Diketopiperazine Compound and Its Preparation Method and Application. CN Patent 108467398 A, 31 August 2018. [Google Scholar]
  192. Yang, X.; Wang, N.; Chen, D.; Kang, Y.; Ma, Y.; Luo, J.; Shi, B.; Long, Y. Preparation of Dicoumarin Derivative as Antimicrobial and Antitumor Agent. CN Patent 108503616 A, 7 September 2018. [Google Scholar]
  193. Zheng, C.; Liao, H.; Huang, G.; Chen, G.; Luo, Y. Method for Preparing Polyketone Compound from Endophytic Fungi of Mangrove, and Application Thereof. CN Patent 108640897 A, 12 October 2018. [Google Scholar]
  194. Wang, C.; Shao, C.; Shi, T.; Qi, J. Marine Fungi Derived from Dichotella Gemmacea and Its Application in Preparing Antimicrobial Drug. CN Patent 108728367 A, 2 November 2018. [Google Scholar]
  195. Xu, J. Pestalotiopyrone M with Immunosuppressive Activity and Preparation Method and Application Thereof. CN Patent 108913731 A, 30 November 2018. [Google Scholar]
  196. He, Q.; Zeng, Q.; Liu, S.; Zhou, H.; Meng, J.; Qi, S.; Zhang, H.; Shao, Y. Metabolite Product of Fusarium Proliferatum as Endophytic Fungus of Ginkgo Biloba and Application Thereof in Antibiosis. CN Patent 109082445 A, 25 December 2018. [Google Scholar]
  197. She, Z.; Wu, Y.; Liu, Z.; Huang, X. Mangrove Endophytic Fungus-Derived Bisabolane Sesquiterpene Compounds and Preparation Method and Application Thereof in Preparation of Anti-Type II Diabetes Drug. CN Patent 109096056 A, 28 December 2018. [Google Scholar]
  198. Murali, T.S.; Satyamoorthy, K.; Bhat, D.V. A Method of Producing Colchicine from an Endophytic Phomopsis Using Epigenetic Modifiers. IN Patent 201641023516 A, 12 January 2018. [Google Scholar]
  199. Aharwal, R.P.; Kumar, S.; Sandhu, S.S. 2′-Hydroxygenistein: Novel Antibacterial Compound from Phoma Sp. Rp1 and Production Thereon. IN Patent 201721003140 A, 8 March 2018. [Google Scholar]
  200. Zhang, Y.; Xie, J.; Wu, Y.; Zhang, M.; Zhang, T. Macrolide Compound and Its Application in Preparing Drugs for Controlling Plant Pathogenic Germs. CN Patent 109111422 A, 1 January 2019. [Google Scholar]
  201. Ai, H.; Wang, W.; Zhang, X.; Feng, T.; He, J.; Li, Z. Preparation of Compound E1011 from Potato Endophytic Fungi Fermentation Product. CN Patent 109180635 A, 11 January 2019. [Google Scholar]
  202. Yan, C.; Liu, H.; Liu, W.; Li, J. Method for Preparing Diphenolic Acid Compound Derived from Santalum Album Endophytic Fungi, and Application Thereof in Preparing Antimicrobial Drug. CN Patent 109206337 A, 15 January 2019. [Google Scholar]
  203. Qin, J. Method for Preparing High Purity Paclitaxel. CN Patent 109232481 A, 18 January 2019. [Google Scholar]
  204. Zhu, X.; Shi, A.; Chen, W.; Tan, L.; Liu, L. Fusarium Oxysporum DCLZJ-4 Strain Producing Paris Polyphylla Saponins and Application Thereof in Preparing Hemostatic Drugs. CN Patent 109234175 A, 18 January 2019. [Google Scholar]
  205. Mao, Z.; Shan, T.; Wang, J.; Zhang, W.; Sun, C.; Wu, H.; Zhang, C. Rapid Separation Method of Secondary Metabolite from Endophytic Fungi of Eucalyptus Exserta, and Its Application in Resistance to Pseudomonas Syringae and Pseudomonas Solanacearum. CN Patent 109265397 A, 25 January 2019. [Google Scholar]
  206. Liu, H.; Yan, C.; Li, J. Method for Preparing 1,4-Naphthoquinone Compound Derived from Mangrove Endophytic Fungi, and Application as Anti-Inflammatory Agents. CN Patent 109293494 A, 1 February 2019. [Google Scholar]
  207. Zhang, C.; Wei, X.; Liu, B.; Feng, C. Microbial Preparation Method of Suberogorgin. CN Patent 109439705 A, 8 March 2019. [Google Scholar]
  208. Liu, H.; Zhang, W.; Tan, H.; Chen, Y.; Li, S.; Li, H. Compound Cerrenin D, Preparing Method Thereof, and Application Thereof in Preparing Antitumor Drug. CN Patent 109456191 A, 12 March 2019. [Google Scholar]
  209. Ding, Z.; Zhou, H.; Yang, Y.; Duan, R. Penicillium and Fermentation Method for Production of Penicillic Acid. CN Patent 109456899 A, 12 March 2019. [Google Scholar]
  210. Zheng, C.; Huang, G.; Bai, M.; Chen, G.; Wang, B. Endophytic Fungi of Bruguiera Sexangula Var.Rhynchopetala and Its Application in Preparation of Active Terpenoids Crystal Compounds with Insecticidal Effect. CN Patent 109486685 A, 19 March 2019. [Google Scholar]
  211. Ji, N.; Song, Y. Nitrogen-Containing Cyclonerolane Sesquiterpene Derivative, Its Preparation and Application. CN Patent 109503414 A, 22 March 2019. [Google Scholar]
  212. Ji, N.; Song, Y. Cyclonerolane Type Hydroxamic Acid Derivative and Its Preparation and Application. CN Patent 109503428 A, 22 March 2019. [Google Scholar]
  213. Ji, N.; Song, Y. Preparation of Bicyclic Cyclonerolane Type Sesquiterpene Derivative for Inhibiting Microalgae. CN Patent 109503535 A, 22 March 2019. [Google Scholar]
  214. Li, H.; Chen, S.; Zhang, W.; Liu, H.; Li, S. Process for Preparation of Guanacastane Compounds, and Their Application in Preparation of Antibacterials. CN Patent 109503623 A, 22 March 2019. [Google Scholar]
  215. Zheng, C.; Huang, G.; Bai, M.; Chen, G.; Wang, B. Preparation of Isocoumarins from Mangrove Endophytic Fungi as Pesticides. CN Patent 109553600 A, 2 April 2019. [Google Scholar]
  216. He, L.; Huang, X.; She, Z. Anthraquinone Metabolite Derived from Endophytic Fungi of Mangrove Forest in the South China Sea and Its Preparation Method and Application in Preparation of Dye. CN Patent 109651125 A, 19 April 2019. [Google Scholar]
  217. Liu, H.; Zhang, W.; Tan, H.; Chen, Y.; Guo, H.; Li, H.; Li, S.; Liu, Z. Compounds Cytorhizin B and Cytorhizin C, and Its Preparation Method and Application in Preparing Drug for Treating Tumor. CN Patent 109776561 A, 21 May 2019. [Google Scholar]
  218. Zhang, Y.; Xu, Z.; Chen, H.; Jiang, D. Plant Endophytic Fungi and Its Application in Preparing Phenolic Acid Compound by Fermentation. CN Patent 109810906 A, 28 May 2019. [Google Scholar]
  219. Ji, N.; Song, Y. Acetylated Nitrogen-Containing Ring Nerol Sesquiterpene Derivative and Its Preparation Method and Application. CN Patent 109956883 A, 2 July 2019. [Google Scholar]
  220. Liu, L.; Chen, B.; Wu, Z.; Chen, S.; Li, J.; Lin, Y. Incarvillea Younghusbandii Endophytic Fungus Onygenales X117, Preparation Method of Its Fermentation Product Gymnoascolide A and Application in Preparing Anti-Inflammatory Drugs. CN Patent 109971652 A, 5 July 2019. [Google Scholar]
  221. Zhang, P.; Yuan, X.; Li, P.; Zhang, Z.; Du, Y.; Liu, X. Tobacco Endophytic Fungus and Application Thereof in Preparing Ergosterol 5,8-Peroxide. CN Patent 109971651 A, 5 July 2019. [Google Scholar]
  222. Tian, Y.; Li, Y. Endophytic Chaetomium Globosum HQ-1 from Astragalus Propinquus and Application in Antifungal and Antibacterial. CN Patent 109971655 A, 5 July 2019. [Google Scholar]
  223. Gao, K.; Long, Y.; Tang, T.; Zhou, M. Compound Bipolahydroquinone C, Its Preparation from Lycium Barbarum Endophytic Fungus Bipolaris Sp.L1-2 Fermentation Culture and Application in Antineoplastic Drug for Treating Human Pulmonary Squamous Carcinoma and Breast Carcinoma. CN Patent 109988181 A, 9 July 2019. [Google Scholar]
  224. Ye, Y.; Zhao, S.; Yan, W. Preparation of Alterlactone and Its Application as Agricultural Bactericide for Controlling Plant Diseases. CN Patent 110093383 A, 6 August 2019. [Google Scholar]
  225. Wen, L.; Chen, G.; Wu, G. Cyclic Depsipeptide Compound in Endophytic Fungi of Mangrove, and Its Preparation Method and Application in Preparing Drug for Treating Tumor. CN Patent 110218200 A, 10 September 2019. [Google Scholar]
  226. Zheng, C.; Huang, G.; Bai, M.; Chen, G. Preparation of Butyrolactones Derived from Mangrove Endophytic Fungi. CN Patent 110229127 A, 13 September 2019. [Google Scholar]
  227. Zheng, C.; Huang, G.; Liao, H.; Mei, R. Bruguiera Sexangula Var.Rhynchopetala Endophytic Fungi Derived Benzopyrone Derivative and Preparation Method and Application Thereof. CN Patent 110257255 A, 20 September 2019. [Google Scholar]
  228. Zhu, B.; Qin, L.; Zhang, Q.; Yang, K.; Wu, W.; Yang, Y.; Dong, S.; Ma, X. Atractylodes Macrocephala Endophytic Fungi and Application Thereof. CN Patent 110257260 A, 20 September 2019. [Google Scholar]
  229. Shu, S.; Cui, L.; Yan, L. Endogenetic Colletotrichum Boninense of Huperzia Serrata for Producing Huperzine A. CN Patent 110272828 A, 24 September 2019. [Google Scholar]
  230. Huang, G.; Zheng, C.; Liao, H.; Mei, R. Tetralone Derivative from Rhizophora Apiculata Blume b. Sexangula Var. Rhynchopetala Endophytic Fungi and Preparation Method and Application Thereof. CN Patent 110283728 A, 27 September 2019. [Google Scholar]
  231. Yin, J.; Xiao, J.; Zhan, Y.; Xu, Z.; Li, L.; Wang, Y.; Zhang, Y.; Li, Y. Endophytic Fungus Strain for Producing Multiple Fatty Acids and Application Thereof. CN Patent 110295116 A, 1 October 2019. [Google Scholar]
  232. Chen, Y.; Yang, X.; Xiao, J.; Lu, H.; Zhou, R.; Liang, M.; Li, Q.; Deng, S.; Tan, Y. Taxus Media Endophytic Fungus Crude Extract and Application Thereof. CN Patent 110302215 A, 8 October 2019. [Google Scholar]
  233. Li, H.; Zhang, Y.; Wang, K.; Li, Z.; Dong, X.; Li, X.; Li, P.; Shan, Y. Endophytic Fungus of Citrus Aurantium Capable of Producing Hesperidin Enzyme and Method for Producing Hesperidin Enzyme by Fermentation Thereof. CN Patent 110438015 A, 12 November 2019. [Google Scholar]
  234. Lou, H.; Li, G.; Tian, C.; Gao, H. Method of Fermentation of Plant Endophytic Fungi to Produce Fusidic Acid. CN Patent 110484588 A, 22 November 2019. [Google Scholar]
  235. Xiao, J.; Li, J.; Liu, Y.; Qin, J.; Yan, L.; Guo, J.; Nian, M.; Luan, H.; Li, R.; Jiang, D.; et al. A Kind of Herba Epimedii Endophytic Bacteria, Culture Method and Its Metabolite. CN Patent 110511876 A, 29 November 2019. [Google Scholar]
  236. Zhang, H.; Pan, R.; Hua, Y.; Chen, J.; Wei, B.; Wang, H. α-Pyrone Compound, Its Preparation Method, Strain and Application in Tumor Cell Activity Inhibitor Preparation. CN Patent 110563740 A, 13 December 2019. [Google Scholar]
  237. Kumar, S.; Prasad, A.R.; Sandhu, S.S. Production of Novel Antibacterial Compound Fraxidin from Aspergillus Japonicus Sk1. IN Patent 201721002537 A, 24 May 2019. [Google Scholar]
  238. Kusari, S.; Singh, S.; Jayabaskaran, C. Biotechnological Potential of Plant-Associated Endophytic Fungi: Hope versus Hype. Trends Biotechnol. 2014, 32, 297–303. [Google Scholar] [CrossRef] [PubMed]
  239. Luo, S.-L.; Dang, L.-Z.; Li, J.-F.; Zou, C.-G.; Zhang, K.-Q.; Li, G.-H. Biotransformation of Saponins by Endophytes Isolated from Panax Notoginseng. Chem. Biodivers. 2013, 10, 2021–2031. [Google Scholar] [CrossRef]
  240. Ying, Y.-M.; Shan, W.-G.; Zhan, Z.-J. Biotransformation of Huperzine A by a Fungal Endophyte of Huperzia Serrata Furnished Sesquiterpenoid–Alkaloid Hybrids. J. Nat. Prod. 2014, 77, 2054–2059. [Google Scholar] [CrossRef]
  241. Zeng, W.L.; Li, W.K.; Han, H.; Tao, Y.Y.; Yang, L.; Wang, Z.T.; Chen, K.X. Microbial Biotransformation of Gentiopicroside by the Endophytic Fungus Penicillium Crustosum 2T01Y01. Appl. Environ. Microbiol. 2014, 80, 184–192. [Google Scholar] [CrossRef] [Green Version]
  242. Bier, M.C.J.; Medeiros, A.B.P.; Soccol, C.R. Biotransformation of limonene by an endophytic fungus using synthetic and orange residue-based media. Fungal Biol. 2017, 121, 137–144. [Google Scholar] [CrossRef]
  243. Kim, Y.J.; Zhang, D.; Yang, D.C. Biosynthesis and biotechnological production of ginsenosides. Biotechnol. Adv. 2015, 33, 717–735. [Google Scholar] [CrossRef]
  244. Li, B.; Yang, Y.; Chen, L.; Chen, S.; Zhang, J.; Tang, W. 18α-glycyrrhetinic acid monoglucuronide as an anti-inflammatory agent through suppression of the NF-ΚB and MAPK signaling pathway. Medchemcomm 2017, 8, 1498–1504. [Google Scholar] [CrossRef]
  245. Lv, G.; Zhang, W.; Sun, X. Ginseng Endophytic Absidia Glauca and Its Application to Prepare Ginsenoside Rd by Transformation of Ginsenoside Rb1. CN Patent 102080048 A, 1 June 2011. [Google Scholar]
  246. Lv, G.; Zhang, W.; Sun, X. Manufacture of Gensenoside Rd from Rb1 with Ginseng Endophyte Zygorhynchus Moelleri. CN Patent 102080049 A, 1 June 2011. [Google Scholar]
  247. Du, X.; Mou, J.; Meng, F. Fusarium Sp. C39 Isolated from Dioscorea Nipponica and Its Application in Preparing Diosgenin. CN Patent 102154123 A, 1 June 2011. [Google Scholar]
  248. Yi, Y.; Liu, H.; Xia, B. Microbial Transformation of Resveratrol from Polygonin in Polygonum Cuspidatum by Fermentation with Penicillium Oxalicum. CN Patent 102199548 A, 28 September 2011. [Google Scholar]
  249. Yi, Y.; Liu, H.; Xia, B. Polygonum Cuspidatum Stem Endophyte Penicillium Oxalicum J1 with Activity to Transform Polydatin into Resveratrol. CN Patent 102212486 A, 12 October 2011. [Google Scholar]
  250. Zhao, G.; Yang, H.; Liu, J.; Lu, H. Preparation of Tobacco Spice by Biotransformation of Raisin Extract with Penicillium Sp. EFCI-24. CN Patent 102392050 A, 28 March 2012. [Google Scholar]
  251. Tang, Y.; Bai, J. Thio-Substituted Podophyllotoxin-like Derivative with Antitumor Activity, Its Biotransformation, Separation and Purification Method. CN Patent 102757443 A, 31 October 2012. [Google Scholar]
  252. Liu, S. Method for Transforming Polydatin into Resveratrol. CN Patent 103695478 A, 2 April 2014. [Google Scholar]
  253. Zhang, Z.; Gao, B.; Zhu, D.; Li, P.; Yan, R.; Wang, Y. An Endophytic Fungus for Bioconversion of Glycyrrhizic Acid into Glycyrrhetinic Acid Glucuronide. CN Patent 103981104 A, 13 August 2014. [Google Scholar]
  254. Zhu, D.; Li, P.; Zhang, Z.; Gao, B. Oryza Rufipogon Endophytic Fungus for Converting Glycyrrhizic Acid into GAMG. CN Patent 103992953 A, 20 August 2014. [Google Scholar]
  255. Cui, X.; Yang, X.; Guo, C.; Chen, Z.; Qu, Y.; Yang, Y.; Liu, D.; Wang, C. Plant Endophytic Fungi from Xylariales and Its Application. CN Patent 106591142 A, 26 April 2017. [Google Scholar]
  256. Zhu, D.; Cui, Q.; Xiao, Y.; Wu, W.; Wang, Y.; Chang, J.; Zhang, Z. Dongxiang Oryza Rufipogon Endophytic Fungi for Efficiently Converting Glycyrrhizic Acid to Produce Glycyrrhetinic Acid Mono-Glucuronide and Its Application. CN Patent 106701604 A, 24 May 2017. [Google Scholar]
  257. Li, W.; Wang, L.; Wang, J.; Zhang, C.; Tang, C.; Wang, J. Transformation of Andrographolide Diterpenoids by Endophytic Fungi. CN Patent 106893677 A, 27 June 2017. [Google Scholar]
  258. Xu, L.; Wang, Z.; Yang, L.; Li, W.; Han, H. Method for Biotransformation by Using Dian Radix Gentianae Endophytic Fungus. CN Patent 107034253 A, 11 August 2017. [Google Scholar]
  259. Fu, Y.; Niu, L.; Ge, Q.; Jiao, J.; Guo, N.; Wang, X.; Wang, W. Fusarium Proliferatum for Efficiently Transforming Panax Notoginseng Ginsenoside Rb1 to Rd and Application. CN Patent 107312720 A, 3 November 2017. [Google Scholar]
  260. Zhao, J.; Wu, J.; Niu, S.; Liu, Q.; Zhu, Y. Bacterial Strain for Specifically Synthesizing Testolactone and ADD by Efficiently Converting 4AD and Application Thereof. CN Patent 108707553 A, 26 October 2018. [Google Scholar]
  261. Lei, F.; Zhang, A.; Chen, C.; Zhang, L. Method for Converting Ginsenoside Rb1 into Rare Ginsenoside by Panax Ginseng Endophyte. CN Patent 109536561 A, 29 March 2019. [Google Scholar]
  262. Yin, J.; Zhan, Y.; Xiao, J.; Xu, Z.; Sun, J.; Zhang, Y.; Wang, Y.; Li, Y. Endophytic Fungus Strain for Efficiently Bioconverting Betulinic Acid and Application Thereof. CN Patent 110527632 A, 3 December 2019. [Google Scholar]
  263. Li, H.; Zhang, Y.; Wang, K.; Li, Z.; Dong, X.; Li, X.; Li, P.; Shan, Y. Octagonal Endophytic Fungus and Method for Converting Trans-Anethole into Isovanillic Acid by Using Same. CN Patent 110423697 A, 8 November 2019. [Google Scholar]
  264. Majeed, M.; Majeed, A.; Thajuddin, N.; Arumugam, S.; Nagabhushanam, K.; Ali, F.; Adams, S.J.; Thomas, S.M.; Krishnamurthy, K.V.; Moothedath, J.; et al. Microbial Bioconversion of Curcumin to Calebin A. U.S. Patent 20190264295 A1, 29 August 2019. [Google Scholar]
  265. Bedir, E.; Ballar Kirmizibayrak, P.; Ekiz, G.; Yilmaz, S.; Duman, S.; Kucuksolak, M. Production Method of Telomerase Activators by Biotransformation with Endophytic Fungi and Telomerase Activators Obtained by This Method. WO Patent 2019070219 A2, 11 April 2019. [Google Scholar]
  266. Newman, D.J.; Cragg, G.M. Plant Endophytes and Epiphytes: Burgeoning Sources of Known and “Unknown” Cytotoxic and Antibiotic Agents? Planta Med. 2020. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  267. Cragg, G.M.; Newman, D.J. Natural Products: A Continuing Source of Novel Drug Leads. Biochim. et Biophys. Acta-Gen. Subj. 2013, 1830, 3670–3695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  268. Chen, L.; Zhang, Q.Y.; Jia, M.; Ming, Q.L.; Yue, W.; Rahman, K.; Qin, L.P.; Han, T. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds. Crit. Rev. Microbiol. 2016, 42, 454–473. [Google Scholar] [CrossRef] [PubMed]
  269. Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803. [Google Scholar] [CrossRef]
  270. Paclitaxel Market Size, Share, Forecast to 2021 | Research Cosmos. Available online: https://www.researchcosmos.com/reports/paclitaxel-market-report-by-indications-breast-cancer-ovarian-cancer-cervical-cancer-prostat/9759991 (accessed on 16 March 2020).
  271. Resveratrol Market-Global Industry Analysis, Size and Forecast, 2018 to 2028. Available online: https://www.futuremarketinsights.com/reports/resveratrol-market (accessed on 16 March 2020).
  272. Protocolo de Nagoya sobre Acceso a los Recursos Genéticos y Participación Justa y Equitativa en los Beneficios que se Deriven de su Utilización al Convenio sobre la Diversidad Biológica; Secretaría del Convenio sobre la Diversidad Biológica; Programa de las Naciones Unidas para el Medio Ambiente: Montreal, QC, Canada, 2011.
Jof 06 00058 g001 550
Figure 1. Progression on the patents and fields of application in the periods 2001–2009 compared to 2010–2019. x-axis year; y-axis numbers of patents.
Figure 1. Progression on the patents and fields of application in the periods 2001–2009 compared to 2010–2019. x-axis year; y-axis numbers of patents.
Jof 06 00058 g001
Jof 06 00058 g002 550
Figure 2. Number of registered patents from 2001 to 2019 linked to endophytic secondary metabolites and biotransformation processes through endophytic fungi.
Figure 2. Number of registered patents from 2001 to 2019 linked to endophytic secondary metabolites and biotransformation processes through endophytic fungi.
Jof 06 00058 g002
Jof 06 00058 g003 550
Figure 3. Number of patents reported for various endophytic fungi by genera.
Figure 3. Number of patents reported for various endophytic fungi by genera.
Jof 06 00058 g003
Table
Table 1. Endophytic fungi and their methods of production of natural products.
Table 1. Endophytic fungi and their methods of production of natural products.
Patent No.EndophyteHost 1Patent DetailsRef.
EP1142986A2Neotyphodium sp.Not disclosedChanoclavine (1)-production.[14]
US6329193B1Cladosporium macrocarponTaxus spp.Production of taxol.[15]
CN1421522AAlternaria sp.Erigeron sp.Production of breviscapine B (2) and other flavonoids for the treatment of cardiovascular diseases and for preparing antitumor medicine.[16]
US6638742B1Alternaria sp.Alnus rubra, Corylus sp., Cytisus scoparius, Ginkgo sp.Methods for obtaining and recovering taxanes, including paclitaxel (3), from novel sources.[17]
US6613738B1Cryptosporiopsis cf. quercinaTripterigeum wilfordiiIsolation of cryptocandin possessing antifungal activity.[18]
US20040185031A1Muscodor vitigenusPaullinia paullinioidesNovel fungi that produces naphthalene and applications.[19]
US20040206697A1Muscodor albusCinnamon treeNovel fungi and production of organic volatile antibiotics effective in the treatment of human and animal waste.[20]
US20040248265A1Phialocephala fortiniiPodophyllum sp.Identification of podophyllotoxin-producing fungi and methods for recovering podophyllotoxin (4) from such fungi.[21]
WO2004106487A2Neotyphodium loliiPooideae grassProduction of janthitrem epoxide (5) compounds in combination with ryegrass instead of compounds that affect the health and performance of grazing animals.[22]
CN1624103AMix of Taxus endophytesTaxus chinensisIncrease the production of taxol and taxol precursors.[23]
US6911338B2Muscodor sp.Cinnamomum zeylanicum, Grevillea pteridifoliaProduction of organic volatile antibiotics with activity on specific plant pathogens, bacteria, nematodes and insects.[24]
CN1850765AHalorosellinia sp.mangroveObtaining quinone compounds (6–7) with antitumor activity.[25]
US20060134762A1Fungal strain MTCC 5124Mappia sp.New source in the form of a novel endophytic fungal strain for the production of camptothecin (8) and camptothecinioids and an improved process for producing these.[26]
US7070985B2Muscodor albusCinnamomum zeylanicumNovel fungi and production of organic volatile antibiotics effective in the treatment of human and animal waste products.[27]
CN1896232AFusarium sp.Ginkgo bilobaProduction of plasmin.[28]
CN1948459ACladosporium sp.Parthenocissus tricuspidataeProduction of resveratrol (9).[29]
CN1951907AAspergillus nigerEuphorbia sp.Preparation of compound 2,3-diamino-6-hydroxy-benzoic acid-2-ethyl-hexyl ester (10), including method, and its application in pharmacy.[30]
CN101037656ATrichoderma harzianumIlex cornutaPreparation of the sesquiterpenoids trichotec-9-en-4-ol, 12, 13, epoxy-, and 4β-acetate (11) as pesticides.[31]
CN101041840ATrichoderma harzianumIlex cornutaPreparation of the sesquiterpenoids trichotec-9-en-4-ol, 12, 13, epoxy-, and 4β-acetate as pesticides.[32]
US7192939B2Pestalotiopsis microsporaTerminalia morobensisNovel fungi strains capable of producing novel antioxidant and antimycotic agents[33]
CN101195804AAcremonium endophytiumHuperzia serrataProduction of huperzine A (12) analogs through strain liquid fermentation of the endophytic fungi.[34]
CN101234951AAspergillus clavatonanicusmangroveProduction of biphenyl compound (13) including preparation method and application.[35]
CN101275116AMix of endophytesHuperzia serrataPreparation of huperzine A.[36]
CN101240249AFusarium sp.Dioscorea zingiberensisProduction of beauvericin (14) description of its antibacterial activity.[37]
CN101280279APhomopsis sp.Acer ginnalaProduction of gallic acid (15).[38]
US7341862B2Muscodor albusCinnamomum zeylanicumNovel fungi and production of organic volatile antibiotics effective in the treatment of human and animal waste products.[39]
CN101412971AFusarium sp.Paris polyphylla var. yunnanensisProduction of 5α, 8α-ergosterol peroxide-6, 22-diene-3β-ol (16), ergosterol-8(9), 22-diene-3β, 5α, 6β, 7α-tetraol (17), and succinic acid (18) as antimicrobial active ingredients.[40]
CN101468977APhomopsis sp.Azadirachta indicaNovel pseudo-phomallactone (19) antibacterial compound from fermentation products of an endophytic fungus strain.[41]
CN101468996APhomopsis sp.Azadirachta indicaSource of ten-membered lactone 7α-acetoxy-multiplolide A (20) and its applications.[42]
CN101481379AChaetomium globosumGinkgo bilobaObtaining chaetomugilin D (21) from an acetic acid ethyl ester extract of fermentation liquor.[43]
CN101486974AAspergillus nigerTaxus cuspidataProduction of taxol from endophytic fungus.[44]
CN101503658ANot disclosedLocoweedSeparation of an endophytic fungus producing swainsonine (22).[45]
CN101525611AFusarium sp.Chrysanthemum sp.Plasmin preparation.[46]
CN101586082AAspergillus candidusTaxus x mediaProduction of taxol. A method for preparing taxol is also given.[47]
US20090142816A1Gliocadium sp.Eucryphia cordifoliaProduction of volatile compounds and hydrocarbons to generate biofuels.[48]
CN101619291AChaetomium cupreumMacleaya cordataPreparation of 3,3′ 6,6′-tetrahydroxy-4,4′-dimethyl-1,1-bi(cyclohexa-3,6-diene)-2,2′,5,5′-tetraone (23) with antitumor properties.[49]
CN101669939ANot disclosedMangroveEnniatin compound (24) that aids in the preparation of anti-tubercle drugs.[50]
CN101701230AFusarium proliferatumMangroveImproving the output of anticancer anthraquinone compound (25) by utilizing different vaccination methods.[51]
CN101875905AShiraia bambusicolaPhyllostachys edulis seedHigh-yield hypocrellin-producing strain that carries out hypocrellin (26) production by fermentation.[52]
CN101914452APenicillium chrysogenumNot disclosedHuperzine A-producing strain.[53]
KR2010104252AScolecobasidium tshawytschaeSoybeanGibberellin (27) production using soybean endophyte.[54]
WO2010062159A1Aspergillus sp.Garcinia scortechiniiCyclic peptides with utility in anticancer treatments.[55]
CN101942393AShiraia sp.Huperzia serrataProduction of huperzine A.[56]
CN102080110ANot disclosedNothapodytes nimmonianaTechnical process for synthesizing a camptothecin sugar derivative.[57]
CN102080111ANot disclosedIcacinaceae plantMethod for endophyte induction to produce 10-hydroxy camptothecin (28).[58]
CN102080112ANot disclosedIcacinaceae plantMethod for endophyte induction to manufacture of 9-methoxycamptothecin (29).[59]
CN102154116APhomopsis wenchengensisNot disclosedManufacture of agricultural fungicide (30).[60]
CN102168017AColletotrichum gloeosporioidesHuperzia serrataHigh-producing strain and method for huperzine A production.[61]
CN102187870AAspergillus oryzaeRed algae Heterosiphonia sp.Use of diterpene alkaloid (31) secondary metabolites as pesticides.[62]
CN102190612AAspergillus oryzaeRed algaePreparation of diterpene alkaloid (32) with bacteriostatic activity that can be used for preparing antimicrobial agents.[63]
CN102190614AAspergillus oryzaeRed algae Heterosiphonia sp.Use of diterpenoid alkaloid (33) as an insecticide agent.[64]
CN102190698AAspergillus oryzaeMarine algaePreparation and application of alga endophytic fungi diterpenoid alkaloid compound (34).[65]
CN102191294AAcremonium endophytiumHuperzia serrataProduction of huperzine A as an anti-senile dementia pharmaceutical ingredient.[66]
CN102190699AAspergillus oryzaeMarine algaePreparation of a diterpene alkaloid-like compound (35) for use as an insecticide.[67]
CN102220247AVerticillium dahliaRadix glycyrrhizaeProduction of glycyrrhetic acid (36).[68]
IN2010DE00131AAspergillus elegansAsparagus racemosusProduction of antimicrobial and anticancer lactone metabolite, including an outline of the process.[69]
JP2011051953ADiaporthe sp.Curcuma sp.Manufacture of neohexa-hydro-curcumin (37).[70]
WO2011146634A1Hypoxylon sp./Nodulisporium sp./Daldinia sp./Muscodor sp.Persea indicaProduction of volatile organic compounds from these fungi.[71]
CA2766412A1Fungal endophytes of Pinus strobusPinus strobusAntifungal metabolites (38–44).[72]
CN102321545APenicillium steckiiTrypterigium wilfordiiProduction of triptolide (45).[73]
CN102417883APhomopsis sp.Camptotheca acuminataProduction and method for preparation of camptothecin.[74]
CN102464634ATrichoderma atrovirideCephalotaxus fortuneiNew compound (46) in secondary metabolites of C. fortunei endophytic fungi and its preparation method and application thereof.[75]
CN102559517AFusarium sp.Podophyllum hexadrumPreparation of podophyllotoxin.[76]
CN102586355AFusarium proliferatumMangroveMethod for producing anticancer anthraquinone compounds.[77]
CN102628018AAspergillus nigerSchisandra chinensisImproved production of the main components schisandrol A (47), schisantherin A (48), deoxyschizandrin (49), schisandrin B (50) from S. chinensis through fermentation.[78]
CN102633616AAlternaria sp.Sarcophyton sp.Preparation of the anthraquinone dimer alterporriol P (51) as an antineoplastic agent.[79]
CN102643167AAspergillus versicolorMarine algaeFermentation preparation and application as an antibacterial and insecticidal agent of albican-11,14-diol (52).[80]
CN102643186AAlternaria sp.Sarcophyton sp.Preparation of the anthraquinone dimers alterporriol Q (53) and alterporriol R (54) for antiviral drugs.[81]
CN102643755APenicillium chrysogenumGlycyrrhiza glabraEndophytic fungus that improves the content of glycyrrhetinic acid by fermenting licorice.[82]
CN102653720AColletotrichum gloeosporioidesHuperzia serrataEndophytic fungus capable of generating huperzine A.[83]
CN102660466AAspergillus penicillioidesSchisandra chinensisImproves the content of the active ingredients of S. chinensis: schizandrin, schisantherin, deoxyschizandrin, and schisandrin B.[84]
CN102660467AFusarium oxysporumGlycyrrhiza glabraFungal strain that produces glycyrrhetinic acid.[85]
CN102676392ATrichoderma atrovirideSalvia miltiorrhizaEndophytic fungus that aids in the production of tanshinone I (55) and tanshinone IIA (56).[86]
CN102701935ATrichoderma longibrachiatumSeaweedPreparation of tetranuclear diterpenoid (57) with pesticidal and bacteriostatic activity.[87]
CN102703327ACladosporium sp.Aconitum leucostomumFungal strain capable of synthesizing aconitine (58) for the preparation of antitumor, anti-inflammatory, and antirheumatic drugs.[88]
CN102719362AAlternaria sp.Merlot grapesFungal strain capable of producing a large amount of resveratrol in the fermentation process.[89]
CN102732427AFusarium proliferatumOxytropis glabraSeparation method for swainsonine-producing endophytic fungus.[90]
CN102732428AFusarium oxysporumCajanus cajanEndophytic fungal strain with a high yield of cajaninstilbene acid (59).[91]
CN102787077AAcremonium sp.Sophora alopecuroidesSynthesis of matrine (60).[92]
CN102807956ACeriporia lacerataCleistocalyx operculatusPreparation of 2′,4′-dihydroxy-6′-methoxyl-3′,5′-dimethylchalcone (61).[93]
WO2012020364A1Fungal strain MTCC 5544Pongamia pinnataDipeptide derivative (62) for the treatment of cancer.[94]
CN103073527APhomopsis sp.Illigera rhodanthaPreparation of libertellenone G (63) as a novel medicine for treating Alzheimer’s disease.[95]
CN103074236ATrichoderma atrovirideCamptotheca acuminataProduction and application of camptothecin.[96]
CN103083290ATrichoderma sp.Not disclosedTrichoderma acid (64) is involved in the preparation of antifungal agents.[97]
CN103087923AChaetomium globosumGinkgo bilobaThe endophytic fungus and metabolite flavipin (65) acts as an antioxidant.[98]
CN103103134AColletotrichum sp.Huperzia serrataProduction of huperzine A.[99]
CN103194502ANodulisporium sylviformeTaxus sp.Separation and purification of taxol by biological fermentation as well as precursors such as baccatin III (66) and cephalomannine (67).[100]
CN103288807ANot disclosedTrypterigium wilfordiiSeparation of alkaloids (68–70) with pharmaceutical application.[101]
CN103360351AXylaria sp.Azadirachta indicaObtaining three isopimarane diterpenoid compounds (71–73) with antifungal activity and potential applications in new agricultural or medical antifungal medicaments.[102]
CN103436451AColletotrichum sp.Cyclocarya paliurusProduction of haematochrome, including its production via a fermentation method.[103]
IN2011DE03381ADiaporthe sp.Pandanus amaryllifoliusAntitubercular diaportheone B analogs (74–75) and their synthesis.[104]
US20130137131A1Nodulisporium sp., Daldinia sp., Hypoxylon sp.Persea indicaSystem and method for producing volatile organic compounds[105]
US20130177596A1Colletotrichum sp.Pteromischum sp.Production of antifungal and immunosuppressive compounds[106]
US20130224315A1Muscodor strobelliNot disclosedProduction of volatile organic compounds and methods of use[107]
US20130252289A1Several fungi such as Nodulisporium sp., Hypoxylon sp., Annulohypoxylon sp., Daldinia sp., Xylaria sp.Thelypteris angustifolia, Persea indica, Citrus aurantifolia, Myroxylon balsamum, Taxodium distichumProduction of volatile organic compounds from microorganisms.[108]
US20130302480A1Muscodor crispansAnanas ananassoidesProduction of compounds with wide range of applications in agriculture, industrial, building, pharmaceutical and/or personal care products.[109]
WO2013164834A1Fusarium solaniTaxus celebicaCost-effective process for commercial production of paclitaxel.[110]
CN103570744AScopulariopsis sp.Carijoa sp.Preparation method for the quinazoline alkaloid compound (76) and its application as a tumor cell growth inhibitor.[111]
CN103627736AFungal strain L1 CGMCC No. 4558Polygonum cuspidatumExtraction of resveratrol from fermented liquor.[112]
CN103642864AShiraia bambusicolaHuperzia serrataPreparation of hypocrellin compounds.[113]
CN103667070ATrichoderma sp.Huperzia serrataPreparation and application of huperzine A.[114]
CN103667072ACeriporia lacerataHuperzia serrataPreparation of 8α, 15α-epoxy-huperzine A (77).[115]
CN103667073APeyronellaea glomerataHuperzia serrataPreparation of pyrrole type (78) liver-protecting medicines.[116]
CN103820331ACeriporia lacerata/Hypoxylon investiensPhlegmariurus sp.Production of huperzine A.[117]
CN103820332APycnoporus sanguineusHuperzia serrataProduction of huperzine A.[118]
CN103911293ABotryosphaeria dothideaTaxus chinensisStrain with a high paclitaxel yield and method for producing paclitaxel.[119]
CN103966109AAspergillus fumigatusSchisandra chinensis fruitEndophytic fungus that is capable of producing protocatechuic aldehyde (79).[120]
CN104031948ADaldinia eschscholziiGracilaria sp.Production of dalesconol A (80) and B (81) as immunosuppressive compounds.[121]
CN104059044ATrichoderma sp./Penicillium sp.MangrovePreparation of a xanthone derivative (82) as a microbial pesticide and fungicide.[122]
CN104073529ANot disclosedTaxus x media seedProduction of taxol.[123]
CN104086522ALasiodiplodia pseudotheobromaeCamptotheca acuminataPreparation of a spiro-dinaphthalene compound (83).[124]
CN104109691ANot disclosedGinkgo bilobaPreparation and dyeing of red pigment haematochrome.[125]
US20140082771A1Nodulosporium spp. or Ascocoryne spp.Lomatia fraseri or Nothofagus cunninghamiiIsolation of antibiotic compound.[126]
CN104293678ACladosporium cladosporioidesForsythia sp.Production of forsythoside A (84), forsythoside B (85), and forsythin (86) and their applications.[127]
CN104357525AAcremonium
dichromosporum		Glycyrrhiza sp.Production of glycyrrhetinic acid by using microbial fermentation.[128]
CN104450528ANot disclosedGardenia jasminoidesMethod for isolation and screening of endophytic fungi and for large-scale preparation of high-purity genipin (87).[129]
CN104450531AFusarium tricinctumFritillaria cirrhosaObtains peiminine (88) and peimisine (89) alkaloids.[130]
CN104593443ABotryosphaeria rhodinaAquilaria sinensisPreparation of agilawood chromone (90–94) components.[131]
CN104726345AMixtures of fungi including Gliocladium sp.Taxus spp.High production of baccatin III.[132]
CN104762348ANot disclosedGastrodia elata/Armillaria melleaPreparation of gastrodin (95).[133]
CN104774774AAspergillus fumigatusGlycyrrhiza sp.Production of pseutorin A (96) as a food preservative.[134]
CN104789613AAlternaria sp.Spiraea salicifoliaExtraction and separation of bacteriostatic component (97) from fermentation broth.[135]
CN104805017AFusarium solaniPinellia sp.Generation and application of β-glucosidase.[136]
CN104877910AEupenicillium brefeldianumNot disclosedPreparation of brefeldin A (98). The compound has antifungal and insecticide activity and is an ideal veterinary and agriculture candidate drug.[137]
CN105039173AMortierella sp.Huperzia serrataFungal strain with a high huperzine A content.[138]
CN105039174AFusarium sp.Paeonia sp.Production of paeonol (99).[139]
CN105039175ATalaromyces sp.Paeonia sp.Production of paeonol.[140]
CN105039176AFusarium sp.Paeonia sp.Production of paeonol.[141]
CN105200091AGeomyces sp.Nerium indicumProduction and application of ethyl vincamine (100).[142]
US20150073048A1Muscodor sp.Ananas ananassoidesProduction of antimicrobial composition and methods of use[143]
WO2015029069A1Trichoderma longibrachiatumBoswellia serrataProduction of brachiatin D (101).[144]
CN105238697AChaetomium sp.Paeonia sp.Production of paeonol with endophytic fungus from peony.[145]
CN105238700AEpicoccum nigrumWild soybeanHigh-yielding oleanolic acid endophyte.[146]
CN105274005AAspergillus fumigatusTaxus x mediaTaxol production.[147]
CN105316238ATrichoderma sp.Taxus chinensisMethod for culturing and screening taxol-producing fungus.[148]
CN105349431APhoma glomerataSalvia miltiorrhizaGeneration and application of salvianolic acid C (102).[149]
CN105400842AFusarium maireiTaxus x media/Valeriana jatamansiIncreases the yield of paclitaxel in an endophytic fungus fermentation product.[150]
CN105505798APhoma glomerataSalvia miltiorrhizaGeneration of ergosterol (103).[151]
CN105506021AAspergillus sp.Not disclosedPreparation of taxol-containing culture.[152]
CN105670940AMucor racemosusHuperzia serrataApplication of a fungal strain with highly efficient expression of huperzine A.[153]
CN105838613AChaetomium globosumCajanus cajanApplication of a fungal strain with a high yield of flavipin.[154]
CN105925646APhomopsis liquidambariMangrovePreparation method for cytochalasin H (104).[155]
CN106010980AParaconiothyrium brasilienseAcrida cinereaStrain capable of producing of perlolyrine (105) and a method for preparation.[156]
CN106047715ATrichoderma sp.Nothapodytes pittosporoidesExtraction of camptothecin.[157]
WO2016034751A1Guignardia mangiferaePersea indicaBiocidal products (106) that are used to control phytopathogens and pest organisms.[158]
CN106432168APenicillium citrinumBruguiera sexangula var. rhynchopetalaPreparation of isocoumarins (107–113) as antibacterial drugs.[159]
CN106434361AAscomycota sp.MangrovePreparation of indanone derivatives (114–115).[160]
CN106497803AFusarium verticillioidesHuperzia serrataFungal strain with huperzine A-producing function and its use in the biosynthesis of medicine for treating Alzheimer´s disease and vascular dementia.[161]
CN106497804AFusarium oxysporumHuperzia serrataProduction of huperzine A and its application in the treatment of dementia.[162]
CN106588944ANeonectria sp.Meconopsis grandisPreparation of compound (116) derived from Tibetan medicine endophytic fungi.[163]
CN106636247ANot disclosedMelia azedarachFermentation extraction of azadirachtin (117).[164]
CN106701594ANeocosmospora sp.Meconopsis grandisProduction of pyrrocidine A (118) and pyrrocidine B (119).[165]
CN106946955APezicula sp.Taxodium distichumProduction of mycotrisaccharide compounds (120–124) that aid in the preparation of drugs for preventing and controlling plant fungal disease.[166]
CN106967622AAspergillus flavusTorreya fargesiiPaclitaxel production.[167]
CN106967623AAspergillus nigerTorreya sp.Production of the taxane compound baccatin III.[168]
CN106978356ANigrospora sphaericaArtemisia argyiPreparation of large amounts of bostrycin (125).[169]
CN107034145APestalotiopsis vismiaeCordyceps sinensisIn vitro production of nucleosides, preferably, adenosine, guanylyl, uridine, and inosine.[170]
CN107058118AAspergillus aculeatusTaxus x mediaEfficient taxol-producing endophytic fungus.[171]
CN107118972AEpicoccum nigrumSolidago canadensisEndophytic fungus capable of generating pectin through liquid fermentation.[172]
CN107129936APenicillium sp.Torreya fargesiiProduction of paclitaxel.[173]
CN107254504AFusarium sp./Bacillus aryabhattaiErigeron breviscapusIncreasing the scutellarin (126) content with microbial agents.[174]
CN107354182APurpureocillium lilacinumGrey green soy beanPreparation of (R)-4-benzyl-2-oxazolidinone (127) by fermentation.[175]
WO2017049353A1Daldinia sp.Pittosporum bicolorProduction of volatile organic compounds as insecticidal and antifungal agents.[176]
WO2017068223A1Stemphylium solaniArtemisia absinthiumTo obtain compounds (128–129) for use as biocides.[177]
CN107686817AAscomycota sp.Fetid marsh fleabaneProduction of ascomylactam compounds (130–131).[178]
CN107723245AFusarium sp.Liriope spicata var. proliferaEndophytic fungi and application in the steroids saponin diosgenin (132) and ruscogenin (133).[179]
CN107723246APenicillium oxalicumLiriope spicata var. proliferaEndophytic fungi and application in the steroid saponin diosgenin and ruscogenin.[180]
CN107723247ACladosporium sp.Liriope spicata var. proliferaEndophytic fungi and application in the steroid saponin diosgenin and ruscogenin.[181]
CN107723248APenicillium sp.Liriope spicata var. proliferaEndophytic fungi and application in the steroid saponin diosgenin and ruscogenin.[182]
CN107739716APenicillium sp.Liriope spicata var. proliferaEndophytic fungi and application in the steroid saponin diosgenin and ruscogenin.[183]
CN107739717ASchizophyllum sp.Liriope spicata var. proliferaEndophytic fungi and application in the steroid saponin diosgenin and ruscogenin.[184]
CN107739718AAspergillus sp.Liriope spicata var. proliferaApplication in the preparation of the steroid saponin diosgenin and ruscogenin.[185]
CN107868757ABjerkandera adustaNot disclosedPreparation of 8α, 15α-epoxy-huperzine A, which has a curative neuroprotective effect.[186]
CN107955793AAspergillus nigerLiriope spicata var. proliferaPreparation of the steroid saponin.[187]
CN108264473APenicillium decumbensNot disclosedPreparation and application of 1-aniline-2-pyrrolidone class compounds (134–135).[188]
CN108277164ADiaporthe sp.Excoecaria agallochaIndene derivative (136) that aids in the preparation of an anti-inflammatory drug[189]
CN108383811AAspergillus tubingensisDecaisnea fargesiiProduction of furanone (137) derivative with good antibacterial activity.[190]
CN108467398ATrichoderma asperellumSeaweedPreparation of diketopiperazine compound (138), which has antibacterial application.[191]
CN108503616AAspergillus tubingensisDecaisnea fargesiiExtraction method and application of a bicoumarin derivative (139).[192]
CN108640897ADaldinia eschscholtziiMangrovePreparation and application of polyketides (140–141).[193]
CN108728367APhoma sp.Coral gorgonian sourcePreparation of antibacterial compounds (142–143).[194]
CN108913731APestalotiopsis sp.Rhizophora stylosaPreparation and application of pestalotiopyrone M (144) which has immunosuppressive activity.[195]
CN109082445AFusarium proliferatumGinkgo sp.Production and application of glycine (145), betaine (146), scopoletin (147), yagaine, rosmarinic acid (148), oxipurinol (149), resveratrol, naringenin (150), catechin (151), taxifolin (152), and xanthohumol (153), which have antibacterial properties.[196]
CN109096056AAspergillus flavusKandelia obovataPreparation of bisabolane sesquiterpene compounds (154-155) as anti-type II diabetes mellitus drugs.[197]
IN201641023516APhomopsis sp.Gloriosa superbaMethod of producing colchicine (156) from an endophyte using epigenetic modifiers.[198]
IN201721003140APhoma sp.Litsea glutinosaIsolation, fermentation, purification, and characterization of the antibacterial compound 2’-hydroxygenistein (157).[199]
CN109111422APenicillium sp.Panax notoginsengMacrolide compounds (158–167) and their application in the prevention and treatment of plant-pathogenic bacteria.[200]
CN109180635AXylaria curtaSolanum tuberosumPreparation and application of compound E1011 (168).[201]
CN109206337AFusarium sp.Santalum albumMethod for preparation of hexichol phenolic acid compounds (169–171) and their application in the preparation of antibacterial compounds.[202]
CN109232481ANot disclosedTaxus chinensisPreparation of high-purity taxol.[203]
CN109234175AFusarium oxysporumParis polyphyllaProduction of chonglou saponin (172–175).[204]
CN109265397ALophiostoma sp.Eucalyptus exsertaFast separating process of fungal secondary metabolites (176–177).[205]
CN109293494ATalaromyces sp.MangroveMethod for preparation of 1, 4-naphtoquinone compounds (178–179) and their application in the preparation of anti-inflammatory drugs.[206]
CN109439705AAspergillus sp.Soft coralMicrobe preparation of subergorgic acid (180).[207]
CN109456191ACerrena sp.Pogostemon cablinPreparation of cerrenin D (181) that is applied in the preparation of antitumor drugs.[208]
CN109456899APenicillium notatumGastrodia elataFermentation and production of penicillic acid (182).[209]
CN109486685APenicillium sp.MangrovePreparation of anti-insect activity terpenes (183–184) as crystalline compounds.[210]
CN109503414ATrichoderma asperellumSeaweedPreparation of one kind of alkane sesquiterpene derivative (185).[211]
CN109503428ATrichoderma asperellumSeaweedPreparation of a cyclonerolane-type hydroxamic acid derivative (186).[212]
CN109503535ATrichoderma asperellumSeaweedPreparation of a bicyclic cyclonerolane type sesquiterpene derivative (187).[213]
CN109503623ATrichoderma koningiopsisMorinda officinalisPreparation and application of guanacaste class compounds (188–189) in the preparation of antibacterial compounds.[214]
CN109553600APenicillium sp.MangrovePreparation and application of isocoumarin class compounds (190–197).[215]
CN109651125AFungal strain ZJY1288 GDMCC No. 60290MangrovePreparation and application of anthraquinone metabolites (198–199)[216]
CN109776561ACytospora rhizophoraeMorinda officinalisPreparation of cytorhizin B (200) and C (201) that are applied in the preparation of antitumor drugs.[217]
CN109810906ABionectria pityrodesTamarix sp.Preparation of phenolic acid compound (202) through fermentation.[218]
CN109956883ATrichoderma asperellumSeaweedPreparation of an azo-cyclo alkane type sesquiterpene derivative (203) produced through an acetylation method.[219]
CN109971652AOnygenales sp.Incarvillea younghusbandiiPreparation of gymnoascolide A (204) in preparing anti-inflammatory drugs.[220]
CN109971651AArthrinium arundinisTobaccoPreparation of 5, 8-peroxyde of ergosterol.[221]
CN109971655AChaetomium sp.Radix astragaliProduction of differanisole A (205).[222]
CN109988181ABipolaris sp.Lycium barbarumPreparation of bipolahydroquinone C (206) that is used as an antineoplastic drug for treating human pulmonary squamous carcinoma and breast carcinoma.[223]
CN110093383AAlternaria sp.Polygonum senegalensePreparation of compound alterlactone (207) that is used as a disinfectant in agriculture.[224]
CN110218200APseudopithomyces sp.Sonneratia caseolarisPreparation of depsipeptide compound (208).[225]
CN110229127Afungal strain TGM112 CGMCC No. 16499MangrovePreparation of butyrolactone compounds (209–211).[226]
CN110257255ADaldinia eschscholtziiMangrovePreparation of chromone derivatives (212–216).[227]
CN110257260ABoeremia exiguaAtractylodis macrocephalaePreparation of the Atractylodes lactones I (217) and II (218).[228]
CN110272828AColletotrichum boninenseHuperzia serrataNew microbe resource for the production of huperzine A industrial fermentation.[229]
CN110283728ADaldinia eschscholtziiMangrovePreparation of tetralone derivatives (219–223).[230]
CN110295116AAspergillus sp.Tamarix sp.Production of a variety of fatty acids and their application.[231]
CN110302215APenicillium sp.Taxus x mediaFungal crude extract, it‘s applications, e.g., as being a source of paclitaxel analog.[232]
CN110438015AAspergillus tamariiCitron orange fruitFungal strain its fermentation to produce hesperidinase.[233]
CN110484588AAcremonium pilosumMahonia sp.Preparation of fusidic acid (224).[234]
CN110511876AIlyonectria cyclaminicolaKorean Epimedium herbThe culture method of this fungal strain and its metabolites epimedins A–C (225–227).[235]
CN110563740AAspergillus fumigatus/Fusarium oxysporumEdgeworthia chrysantha/Stachys japonicaMethods for preparation and application of alpha-pyrone (228).[236]
IN201721002537AAspergillus japonicusAchryranthes asperaProduction of the novel antibacterial compound fraxidin (229).[237]
1 Some patents just provided a common name for the host organism.
Table
Table 2. Endophytic fungi applied for biotransformation.
Table 2. Endophytic fungi applied for biotransformation.
Patent No.EndophyteHost 1Patent DetailsRef.
CN102080048AAbsidia glaucagingsenConversion of ginsenoside Rb1 (230) to prepare ginsenoside Rd (231).[245]
CN102080049AZygorhynchus moelleriPanax gingsenPreparation of ginsenoside Rd from ginsenoside Rb1.[246]
CN102154123AFusarium sp.Dioscorea nipponicaBiotransformation conversion conditions of diosgenin saponins.[247]
CN102199548APenicillium oxalicumPolygonun cuspidatumMicrobial transformation of resveratrol from polydatin (232).[248]
CN102212486APenicillium oxalicumPolygonun cuspidatumConversion of polydatin into resveratrol.[249]
CN102392050APenicillium sp.Not disclosedBiotransformation of raisin extract. Preparation and application in flavoring.[250]
CN102757443ASeveral endophytes featuring Penicillium purpurogenumDysosma sp. or Sabina vulgarisSeparation and purification method for bioconversion of podophyllotoxin into sulfur-substituted derivatives.[251]
CN103695478Afungal strain L1 CGMCC No. 4558Not disclosedConversion of polydatin to resveratrol.[252]
CN103981104AMicrosphaeropsis arundiniswild riceBiotransformation of glycyrrhizinic acid (233) into liquiritin (234).[253]
CN103992953AAspergillus flavuswild riceTransform glycyrrhizic acid into glycyrrhetinic acid monoglucuronide (235).[254]
CN106591142AXylariales sp.Not disclosedConversion of Panax notoginseng saponin to prepare vina-ginsenoside R13 (236), notoginsenoside J (237) and American saponin ginseng L16 (238).[255]
CN106701604AChaetomium globosumwild riceConversion of glycyrrhizic acid into glycyrrhetinic acid monoglucuronide.[256]
CN106893677AFusarium sp.Herba AndrographitisTransformation of andrographolide diterpenoids (239–242).[257]
CN107034253AFusarium oxysporumGentiana sp.Conversion of gentiopicroside (243) into two separate compounds with hepatoprotective activity.[258]
CN107312720AFusarium proliferatumCajanus cajanConversion of ginsenoside Rb1 into ginsenoside Rd and its application.[259]
CN108707553APlectosphaerella cucumerinaHuperzia serrataEfficient conversion of androstenedione to testolactone and androstane diene diketone.[260]
CN109536561AFusarium oxysporumgingsenConversion of ginsenoside Rb1 into the rare ginsenoside CK (244).[261]
CN110527632APhomopsis sp.Not disclosedBioconversion of betulinic acid (245).[262]
CN110423697ALasiodiplodia pseudotheobromaeIllicium verumtrans-trans-Anethole (246) conversion to generate different vanillic acids (247).[263]
US20190264295A1Ovatospora brasiliensisCurcuma sp.Microbial bioconversion of curcuminoids to calebin A (248).[264]
WO2019070219A2Alternaria eureka/Neosartorya hiratsukae/Camarosporium laburnicolaAstragalus condensatus, A. angustifoliusProduction of a telomerase activator, biotransformation with endophytic fungi to obtain new/novel molecules from the saponins from natural sources and method for discovery molecules that increase telomerase enzyme activation.[265]
1 Some patents just provided a common name for the host organism.

Share and Cite

MDPI and ACS Style

Torres-Mendoza, D.; Ortega, H.E.; Cubilla-Rios, L. Patents on Endophytic Fungi Related to Secondary Metabolites and Biotransformation Applications. J. Fungi 2020, 6, 58. https://doi.org/10.3390/jof6020058

AMA Style

Torres-Mendoza D, Ortega HE, Cubilla-Rios L. Patents on Endophytic Fungi Related to Secondary Metabolites and Biotransformation Applications. Journal of Fungi. 2020; 6(2):58. https://doi.org/10.3390/jof6020058

Chicago/Turabian Style

Torres-Mendoza, Daniel, Humberto E. Ortega, and Luis Cubilla-Rios. 2020. "Patents on Endophytic Fungi Related to Secondary Metabolites and Biotransformation Applications" Journal of Fungi 6, no. 2: 58. https://doi.org/10.3390/jof6020058

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop