Chemistry and biology of marine-derived Trichoderma metabolites

doi:10.1007/s13659-024-00433-3

Abstract

Abstract: Marine-derived fungi of the genus Trichoderma have been surveyed for pharmaceuticals and agrochemicals since 1993, with various new secondary metabolites being characterized from the strains of marine animal, plant, sediment, and water origin. Chemical structures and biological activities of these metabolites are comprehensively reviewed herein up to the end of 2022 (covering 30 years). More than 70 strains that belong to at least 18 known Trichoderma species have been chemically investigated during this period. As a result, 445 new metabolites, including terpenes, steroids, polyketides, peptides, alkaloids, and others, have been identified, with over a half possessing antimicroalgal, zooplankton-toxic, antibacterial, antifungal, cytotoxic, anti-inflammatory, and other activities. The research is highlighted by the molecular diversity and antimicroalgal potency of terpenes and steroids. In addition, metabolic relevance along with co-culture induction in the production of new compounds is also concluded. Trichoderma strains of marine origin can transform and degrade heterogeneous molecules, but these functions need further exploration.

Key words: Trichoderma, Metabolite, Terpene, Polyketide, Peptide, Bioactivity

摘要： Marine-derived fungi of the genus Trichoderma have been surveyed for pharmaceuticals and agrochemicals since 1993, with various new secondary metabolites being characterized from the strains of marine animal, plant, sediment, and water origin. Chemical structures and biological activities of these metabolites are comprehensively reviewed herein up to the end of 2022 (covering 30 years). More than 70 strains that belong to at least 18 known Trichoderma species have been chemically investigated during this period. As a result, 445 new metabolites, including terpenes, steroids, polyketides, peptides, alkaloids, and others, have been identified, with over a half possessing antimicroalgal, zooplankton-toxic, antibacterial, antifungal, cytotoxic, anti-inflammatory, and other activities. The research is highlighted by the molecular diversity and antimicroalgal potency of terpenes and steroids. In addition, metabolic relevance along with co-culture induction in the production of new compounds is also concluded. Trichoderma strains of marine origin can transform and degrade heterogeneous molecules, but these functions need further exploration.

关键词: Trichoderma, Metabolite, Terpene, Polyketide, Peptide, Bioactivity

Yin-Ping Song, Nai-Yun Ji. Chemistry and biology of marine-derived Trichoderma metabolites[J]. Natural Products and Bioprospecting, 2024, 14(3): 14-14.

Yin-Ping Song, Nai-Yun Ji. Chemistry and biology of marine-derived Trichoderma metabolites[J]. 应用天然产物, 2024, 14(3): 14-14.

References

1. Persoon CH. Disposita methodica fungorum. Römer’s Neues Mag Bot. 1794;1:81-128.
2. Kirk PM, Cannon PF, Minter DW, Stalpers JA. Anisworth & Bisby’s Dictionary of the Fungi (10th edition). Wallingford: CAB International Publishing; 2008. p. 1–771.
3. Harman GE, Howell CR, Viterbo A, Chet I, Lorito M. Trichoderma species— opportunistic, avirulent plant symbionts. Nat Rev Microbiol. 2004;2:43–56.
4. Samuels GJ. Trichoderma: systematics, the sexual state, and ecology. Phytopathology. 2006;96:195–206.
5. Rossman AY, Seifert KA, Samuels GJ, Minnis AM, Schroers H-J, Lombard L, Crous PW, Põldmaa K, Cannon PF, Summerbell RC, Geiser DM, Zhuang W-Y, Hirooka Y, Herrera C, Salgado-Salazar C, Chaverri P. Genera in Bionectriaceae, Hypocreaceae, and Nectriaceae (Hypocreales) proposed for acceptance or rejection. IMA Fungus. 2013;4:41–51.
6. Bissett J, Gams W, Jaklitsch W, Samuels GJ. Accepted Trichoderma names in the year 2015. IMA Fungus. 2015;6:263–95.
7. Contreras-Cornejo HA, Macías-Rodríguez L, del-Val E, Larsen J. Ecological functions of Trichoderma spp. and their secondary metabolites in the rhizosphere: interactions with plants. FEMS Microbiol Ecol. 2016;92:036.
8. Chen K, Zhuang W-Y. Trichoderma shennongjianum and Trichoderma tibetense, two new soil-inhabiting species in the Strictipile clade. Mycoscience. 2016;57:311–9.
9. Qin W-T, Zhuang W-Y. Seven wood-inhabiting new species of the genus Trichoderma (Fungi, Ascomycota) in Viride clade. Sci Rep. 2016;6:27074.
10. Chen K, Zhuang W-Y. Discovery from a large-scaled survey of Trichoderma in soil of China. Sci Rep. 2017;7:9090.
11. Zhu Z-X, Xu H-X, Zhuang W-Y, Li Y. Two new green-spored species of Trichoderma (Sordariomycetes, Ascomycota) and their phylogenetic positions. MycoKeys. 2017;26:61–75.
12. Weindling R. Trichoderma lignorum as a parasite of other soil fungi. Phytopathology. 1932;22:837–45.
13. Weindling R. Studies on a lethal principle effective in the parasitic action of Trichoderma lignorum on Rhizoctonia solani and other soil fungi. Phytopathology. 1934;24:1153–79.
14. Woo SL, Ruocco M, Vinale F, Nigro M, Marra R, Lombardi N, Pascale A, Lanzuise S, Manganiello G, Lorito M. Trichoderma-based products and their widespread use in agriculture. Open Mycol J. 2014;8:71–126.
15. Singh A, Shukla N, Kabadwal BC, Tewari AK, Kumar J. Review on plant-Trichoderma-pathogen interaction. Int J Curr Microbiol App Sci. 2018;7:2382–97.
16. Vinale F, Sivasithamparam K, Ghisalberti EL, Marra R, Woo SL, Lorito M. Trichoderma–plant–pathogen interactions. Soil Biol Biochem. 2008;40:1–10.
17. Howell CR. Mechanisms employed by Trichoderma species in the biological control of plant diseases: the history and evolution of current concepts. Plant Dis. 2003;87:4–10.
18. Ghisalberti EL, Sivasithamparam K. Antifungal antibiotics produced by Trichoderma spp. Soil Biol Biochem. 1991;23:1011–20.
19. Keswani C, Mishra S, Sarma BK, Singh SP, Singh HB. Unraveling the efficient applications of secondary metabolites of various Trichoderma spp. Appl Microbiol Biotechnol. 2014;98:533–44.
20. Reino JL, Guerrero RF, Hernández-Galán R, Collado IG. Secondary metabolites from species of the biocontrol agent Trichoderma. Phytochem Rev. 2008;7:89–123.
21. Li M-F, Li G-H, Zhang K-Q. Non-volatile metabolites from Trichoderma spp. Metabolites. 2019;9:58.
22. Bai B, Liu C, Zhang C, He X, Wang H, Peng W, Zheng C. Trichoderma species from plant and soil: an excellent resource for biosynthesis of terpenoids with versatile bioactivities. J Adv Res. 2023;49:81–102.
23. Su D, Ding L, He S. Marine-derived Trichoderma species as a promising source of bioactive secondary metabolites. Mini-Rev Med Chem. 2018;18:1702–13.
24. Kobayashi M, Uehara H, Matsunami K, Aoki S, Kitagawa I. Trichoharzin, a new polyketide produced by the imperfect fungus Trichoderma harzianum separated from the marine sponge Micale cecilia. Tetrahedron Lett. 1993;34:7925–8.
25. Song Y-P, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Halogenated and nonhalogenated metabolites from the marine-alga-endophytic fungus Trichoderma asperellum cf44-2. Mar Drugs. 2018;16:266.
26. Song Y-P, Liu X-H, Shi Z-Z, Miao F-P, Fang S-T, Ji N-Y. Bisabolane, cyclonerane, and harziane derivatives from the marine-algaendophytic fungus Trichoderma asperellum cf44-2. Phytochemistry. 2018;152:45–52.
27. Song Y-P, Miao F-P, Yin X-L, Ji N-Y. Nitrogenous cyclonerane sesquiterpenes from an algicolous strain of Trichoderma asperellum. Org Chem Front. 2019;6:3698–704.
28. Song Y-P, Miao F-P, Liu X-H, Yin X-L, Ji N-Y. Cyclonerane derivatives from the algicolous endophytic fungus Trichoderma asperellum A-YMD-9-2. Mar Drugs. 2019;17:252.
29. Fang S-T, Wang Y-J, Ma X-Y, Yin X-L, Ji N-Y. Two new sesquiterpenoids from the marine-sediment-derived fungus Trichoderma harzianum P1–4. Nat Prod Res. 2019;33:3127–33.
30. Song Y-P, Fang S-T, Miao F-P, Yin X-L, Ji N-Y. Diterpenes and sesquiterpenes from the marine algicolous fungus Trichoderma harzianum X-5. J Nat Prod. 2018;81:2553–9.
31. Ma X-Y, Song Y-P, Shi Z-Z, Ji N-Y. Three sesquiterpenes from the marine-alga-epiphytic fungus Trichoderma hamatum Z36–7. Phytochem Lett. 2021;43:98–102.
32. Guo Y-W, Gong B-Q, Yuan J, Li H-J, Mahmud T, Huang Y, Li J-F, Yang D-P, Lan W-J. l-Phenylalanine alters the privileged secondary metabolite production in the marine-derived fungus Trichoderma erinaceum F1–1. J Nat Prod. 2020;83:79–87.
33. Liu X-H, Hou X-L, Song Y-P, Wang B-G, Ji N-Y. Cyclonerane sesquiterpenes and an isocoumarin derivative from the marine-alga-endophytic fungus Trichoderma citrinoviride A-WH-20-3. Fitoterapia. 2020;141: 104469.
34. Zou J-X, Song Y-P, Liu X-H, Li X-N, Ji N-Y. Bisabolane, cadinane, and cyclonerane sesquiterpenes from an algicolous strain of Trichoderma asperelloides. Bioorg Chem. 2021;115: 105223.
35. Song Y, Miao F, Yin X, Ji N. Three nitrogen-containing metabolites from an algicolous isolate of Trichoderma asperellum. Mar Life Sci Technol. 2020;2:155–60.
36. Shi Z-Z, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Trichobisabolins A-H, eight new bisabolane derivatives from the marine-alga-epiphytic fungus Trichoderma asperellum Y6–2. Fitoterapia. 2019;134:372–7.
37. Shi Z-Z, Liu X-H, Song Y-P, Yin X-L, Ji N-Y. Sesquiterpenoids and a steroid from the algicolous Trichoderma brevicompactum. Fitoterapia. 2021;153: 104983.
38. Song Y-P, Miao F-P, Liu X-H, Yin X-L, Ji N-Y. Seven chromanoid norbisabolane derivatives from the marine-alga-endophytic fungus Trichoderma asperellum A-YMD-9-2. Fitoterapia. 2019;135:107–13.
39. Liu X-H, Song Y-P, Wang B-G, Ji N-Y. Sesquiterpenes and lipids from the algicolous fungus Trichoderma atroviride RR-dl-3-9. Phytochem Lett. 2021;45:6–12.
40. Safwan S, Wang S-W, Hsiao G, Hsiao S-W, Hsu S-J, Lee T-H, Lee C-K. New trichothecenes isolated from the marine algicolous fungus Trichoderma brevicompactum. Mar Drugs. 2022;20:80.
41. Yamazaki H, Takahashi O, Kirikoshi R, Yagi A, Ogasawara T, Bunya Y, Rotinsulu H, Uchida R, Namikoshi M. Epipolythiodiketopiperazine and trichothecene derivatives from the NaI-containing fermentation of marine-derived Trichoderma cf. brevicompactum. J Antibiot. 2020;73:559–67.
42. Yamazaki H, Yagi A, Takahashi O, Yamaguchi Y, Saito A, Namikoshi M, Uchida R. Antifungal trichothecene sesquiterpenes obtained from the culture broth of marine-derived Trichoderma cf. brevicompactum and their structure–activity relationship. Bioorg Med Chem Lett. 2020;30:127375.
43. Shi Z-Z, Liu X-H, Li X-N, Ji N-Y. Antifungal and antimicroalgal trichothecene sesquiterpenes from the marine algicolous fungus Trichoderma brevicompactum A-DL-9-2. J Agric Food Chem. 2020;68:15440–8.
44. Shi Z-Z, Fang S-T, Miao F-P, Yin X-L, Ji N-Y. Trichocarotins A-H and trichocadinin A, nine sesquiterpenes from the marine-alga-epiphytic fungus Trichoderma virens. Bioorg Chem. 2018;81:319–25.
45. Song Y-P, Shi X-S, Wang B-G, Ji N-Y. Cadinane and carotane derivatives from the marine algicolous fungus Trichoderma virens RR-dl-6-8. Fitoterapia. 2020;146: 104715.
46. Song Y-P, Miao F-P, Liang X-R, Yin X-L, Ji N-Y. Harziane and cadinane terpenoids from the alga-endophytic fungus Trichoderma asperellum A-YMD-9-2. Phytochem Lett. 2019;32:38–41.
47. Cui J, Shang R-Y, Sun M, Li Y-X, Liu H-Y, Lin H-W, Jiao W-H. Trichodermaloids A-C, cadinane sesquiterpenes from a marine sponge symbiotic Trichoderma sp. SM16 fungus. Chem Biodivers. 2020;17:e2000036.
48. Qin C, Hu Z, Xiong Y, Chen M, Li C, Ding W. A new sesquiterpene derivative from the mangrove endophytic fungus Trichoderma harzianum (strain No. R1). Chem Nat Compd. 2021;57:312–4.
49. Wang Y, Li X-M, Yang S-Q, Zhang F-Z, Wang B-G, Li H-L, Meng L-H. Sesquiterpene and sorbicillinoid glycosides from the endophytic fungus Trichoderma longibrachiatum EN-586 derived from the marine red alga Laurencia obtusa. Mar Drugs. 2022;20:177.
50. Du X-P, Li Y-Y, Lu C-H, Zheng Z-H, Shen Y-M. A novel sesquiterpene glucoside from Trichoderma sp. PT2. Nat Prod Res Dev. 2010;22:544–7.
51. Du F-Y, Ju G-L, Xiao L, Zhou Y-M, Wu X. Sesquiterpenes and cyclodepsipeptides from marine-derived fungus Trichoderma longibrachiatum and their antagonistic activities against soil-borne pathogens. Mar Drugs. 2020;18:165.
52. Li B, Li L, Peng Z, Liu D, Si L, Wang J, Yuan B, Huang J, Proksch P, Lin W. Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus. Bioorg Med Chem. 2019;27:560–7.
53. Miao F-P, Liang X-R, Yin X-L, Wang G, Ji N-Y. Absolute configurations of unique harziane diterpenes from Trichoderma species. Org Lett. 2012;14:3815–7.
54. Zou J-X, Song Y-P, Ji N-Y. Deoxytrichodermaerin, a harziane lactone from the marine algicolous fungus Trichoderma longibrachiatum A-WH-20-2. Nat Prod Res. 2021;35:216–21.
55. Li H, Liu X, Li X, Hu Z, Wang L. Novel harziane diterpenes from deepsea sediment fungus Trichoderma sp. SCSIOW21 and their potential anti-inflammatory effects. Mar Drugs. 2021;19:689.
56. Shi T, Shao C-L, Liu Y, Zhao D-L, Cao F, Fu X-M, Yu J-Y, Wu J-S, Zhang Z-K, Wang C-Y. Terpenoids from the coral-derived fungus Trichoderma harzianum (XS-20090075) induced by chemical epigenetic manipulation. Front Microbiol. 2020;11:572.
57. Zhao D-L, Yang L-J, Shi T, Wang C-Y, Shao C-L, Wang C-Y. Potent phytotoxic harziane diterpenes from a soft coral-derived strain of the fungus Trichoderma harzianum XS-20090075. Sci Rep. 2019;9:13345.
58. Zhang M, Liu J-M, Zhao J-L, Li N, Chen R-D, Xie K-B, Zhang W-J, Feng K-P, Yan Z, Wang N, Dai J-G. Two new diterpenoids from the endophytic fungus Trichoderma sp. Xy24 isolated from mangrove plant Xylocarpus granatum. Chin Chem Lett. 2016;27:957–60.
59. Zou J-X, Song Y-P, Zeng Z-Q, Ji N-Y. Proharziane and harziane derivatives from the marine algicolous fungus Trichoderma asperelloides RR-dl-6-11. J Nat Prod. 2021;84:1414–9.
60. Xie Z-L, Li H-J, Wang L-Y, Liang W-L, Liu W, Lan W-J. Trichodermaerin, a new diterpenoid lactone from the marine fungus Trichoderma erinaceum associated with the sea star Acanthaster planci. Nat Prod Commun. 2013;8:67–8.
61. Yamada T, Suzue M, Arai T, Kikuchi T, Tanaka R. Trichodermanins C-E, new diterpenes with a fused 6-5-6-6 ring system produced by a marine sponge-derived fungus. Mar Drugs. 2017;15:169.
62. Yamada T, Fujii A, Kikuchi T. New diterpenes with a fused 6-5-6-6 ring system isolated from the marine sponge-derived fungus Trichoderma harzianum. Mar Drugs. 2019;17:480.
63. Liang X-R, Miao F-P, Song Y-P, Liu X-H, Ji N-Y. Citrinovirin with a new norditerpene skeleton from the marine algicolous fungus Trichoderma citrinoviride. Bioorg Med Chem Lett. 2016;26:5029–31.
64. Liang X-R, Miao F-P, Song Y-P, Guo Z-Y, Ji N-Y. Trichocitrin, a new fusicoccane diterpene from the marine brown alga-endophytic fungus Trichoderma citrinoviride cf-27. Nat Prod Res. 2016;30:1605–10.
65. Liang X-R, Ma X-Y, Ji N-Y. Trichosordarin A, a norditerpene glycoside from the marine-derived fungus Trichoderma harzianum R5. Nat Prod Res. 2020;34:2037–42.
66. Song Y-P, Shi Z-Z, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Tricholumin A, a highly transformed ergosterol derivative from the alga-endophytic fungus Trichoderma asperellum. Org Lett. 2018;20:6306–9.
67. Li B, Huang Q-X, Gao D, Liu D, Ji Y-B, Liu H-G, Lin W-H. New C13 lipids from the marine-derived fungus Trichoderma harzianum. J Asian Nat Prod Res. 2015;17:468–74.
68. Liu X-H, Ji N-Y. Isolation, identification, and bioactivity of a new triol from algicolous fungus Trichoderma citrinoviride. Chem Bioeng. 2022;39:15–8.
69. Hu X, Gong M-W, Zhang W-W, Zheng Q-H, Liu Q-Y, Chen L, Zhang Q-Q. Novel cytotoxic metabolites from the marine-derived fungus Trichoderma citrinoviride. Heterocycles. 2014;89:189–96.
70. Zhao D-L, Zhang X-F, Huang R-H, Wang D, Wang X-Q, Li Y-Q, Zheng C-J, Zhang P, Zhang C-S. Antifungal nafuredin and epithiodiketopiperazine derivatives from the mangrove-derived fungus Trichoderma harzianum D13. Front Microbiol. 2020;11:1495.
71. Amagata T, Usami Y, Minoura K, Ito T, Numata A. Cytotoxic substances produced by a fungal strain from a sponge: physico-chemical properties and structures. J Antibiot. 1998;51:33–40.
72. Usami Y, Ikura T, Amagata T, Numata A. First total syntheses and configurational assignments of cytotoxic trichodenones A-C. Tetrahedron: Asymm. 2000;11:3711–25.
73. You J, Dai H, Chen Z, Liu G, He Z, Song F, Yang X, Fu H, Zhang L, Chen X. Trichoderone, a novel cytotoxic cyclopentenone and cholesta-7, 22-diene-3β, 5α, 6β-triol, with new activities from the marine-derived fungus Trichoderma sp. J Ind Microbiol Biotechnol. 2010;37:245–52.
74. Qiu P, Ding L, Sun D, He S. A new cyclopentenone derivative from the sponge-associated fungus Hypocrea koningii. Chem Nat Compd. 2018;54:631–3.
75. Sun S, Tian L, Wang Y, Wu H, Lu X, Pei Y. A novel natural product from the fermentation liquid of marine fungus Trichoderma atroviride G20–12. Asian J Trad Med. 2009;4:123–7.
76. Tang X-X, Liu S-Z, Sun Y-Y, He F-M, Xu G-X, Fang M-J, Zhen W, Qiu Y-K. New cyclopentenoneacrylic acid derivatives from a marine-derived fungus Trichoderma atroviride H548. Nat Prod Res. 2021;35:3772–9.
77. Ding L-J, Gu B-B, Jiao W-H, Yuan W, Li Y-X, Tang W-Z, Yu H-B, Liao X-J, Han B-N, Li Z-Y, Xu S-H, Lin H-W. New furan and cyclopentenone derivatives from the sponge-associated fungus Hypocrea Koningii PF04. Mar Drugs. 2015;13:5579–92.
78. Fang F, Zhao J, Ding L, Huang C, Naman B, He S, Wu B, Zhu P, Luo Q, Gerwick WH, Yan X, Wang Q, Zhang Z, Cui W. 5-Hydroxycyclopenicillone, a new β-amyloid fibrillization inhibitor from a sponge-derived fungus Trichoderma sp. HPQJ-34. Mar Drugs. 2017;15:260.
79. Du L, Zhu T, Li L, Cai S, Zhao B, Gu Q. Cytotoxic sorbicillinoids and bisorbicillinoids from a marine-derived fungus Trichoderma sp. Chem Pharm Bull. 2009;57:220–3.
80. Lan W-J, Zhao Y, Xie Z-L, Liang L-Z, Shao W-Y, Zhu L-P, Yang D-P, Zhu X-F, Li H-J. Novel sorbicillin analogues from the marine fungus Trichoderma sp. associated with the seastar Acanthaster planci. Nat Prod Commun. 2012;7:1337–40.
81. Zhang P, Deng Y, Lin X, Chen B, Li J, Liu H, Chen S, Liu L. Anti-inflammatory mono-and dimeric sorbicillinoids from the marine-derived fungus Trichoderma reesei 4670. J Nat Prod. 2019;82:947–57.
82. Liu S-Z, Xu G-X, He F-M, Zhang W-B, Wu Z, Li M-Y, Tang X-X, Qiu Y-K. New sorbicillinoids with tea pathogenic fungus inhibitory effect from marine-derived fungus Hypocrea jecorina H8. Mar Drugs. 2022;20:213.
83. Zaman KAU, Wu X, Sarotti AM, Cao S. New and bioactive polyketides from Hawaiian marine-derived fungus Trichoderma sp. FM652. Nat Prod Res. 2022;36:5984–90.
84. Meng J, Cheng W, Heydari H, Wang B, Zhu K, Konuklugil B, Lin W. Sorbicillinoid-based metabolites from a sponge-derived fungus Trichoderma saturnisporum. Mar Drugs. 2018;16:226.
85. Sperry S, Samuels GJ, Crews P. Vertinoid polyketides from the saltwater culture of the fungus Trichoderma longibrachiatum separated from a Haliclona marine sponge. J Org Chem. 1998;63:10011–4.
86. Rehman SU, Yang L-J, Zhang Y-H, Wu J-S, Shi T, Haider W, Shao C-L, Wang C-Y. Sorbicillinoid derivatives from sponge-derived fungus Trichoderma reesei (HN-2016-018). Front Microbiol. 2020;11:1334.
87. Neumann K, Abdel-Lateff A, Wright AD, Kehraus S, Krick A, König GM. Novel sorbicillin derivatives with an unprecedented carbon skeleton from the sponge-derived fungus Trichoderma species. Eur J Org Chem. 2007;2007:2268–75.
88. Marra R, Nicoletti R, Pagano E, DellaGreca M, Salvatore MM, Borrelli F, Lombardi N, Vinale F, Woo SL, Andolfi A. Inhibitory effect of trichodermanone C, a sorbicillinoid produced by Trichoderma citrinoviride associated to the green alga Cladophora sp., on nitrite production in LPS-stimulated macrophages. Nat Prod Res. 2019;33:3389–97.
89. Sun Y, Tian L, Huang J, Ma H-Y, Zheng Z, Lv A-L, Yasukawa K, Pei Y-H. Trichodermatides A–D, novel polyketides from the marine-derived fungus Trichoderma reesei. Org Lett. 2008;10:393–6.
90. Wang X-H, Xu X-Y, Li Y, Yao F-H, Chen X, Qi S-H, Tao S-H. Secondary metabolites and antimicrobial activities of Hypocrea lixii SCSIO 41520. Nat Prod Res Dev. 2020;32:1522–8.
91. Song F, Dai H, Tong Y, Ren B, Chen C, Sun N, Liu X, Bian J, Liu M, Gao H, Liu H, Chen X, Zhang L. Trichodermaketones A–D and 7-O-methylkoninginin D from the marine fungus Trichoderma koningii. J Nat Prod. 2010;73:806–10.
92. Yamazaki H, Saito R, Takahashi O, Kirikoshi R, Toraiwa K, Iwasaki K, Izumikawa Y, Nakayama W, Namikoshi M. Trichoketides A and B, two new protein tyrosine phosphatase 1B inhibitors from the marine-derived fungus Trichoderma sp. J Antibiot. 2015;68:628–32.
93. Nuansri S, Rukachaisirikul V, Rungwirain N, Kaewin S, Yimnual C, Phongpaichit S, Preedanon S, Sakayaroj J, Muanprasat C. α-Pyrone and decalin derivatives from the marine-derived fungus Trichoderma harzianum PSU-MF79. Nat Prod Res. 2022;36:5462–9.
94. Lai C, Chen J, Liu J, Tian D, Lan D, Liu T, Wu B, Bi H, Tang J. New polyketides from a hydrothermal vent sediment fungus Trichoderma sp. JWM29-10-1 and their antimicrobial effects. Mar Drugs. 2022;20:720.
95. Yamada T, Mizutani Y, Umebayashi Y, Inno N, Kawashima M, Kikuchi T, Tanaka R. Tandyukisin, a novel ketoaldehyde decalin derivative, produced by a marine sponge-derived Trichoderma harzianum. Tetrahedron Lett. 2014;55:662–4.
96. Yamada T, Umebayashi Y, Kawashima M, Sugiura Y, Kikuchi T, Tanaka R. Determination of the chemical structures of tandyukisins B–D, isolated from a marine sponge-derived fungus. Mar Drugs. 2015;13:3231–40.
97. Suzue M, Kikuchi T, Tanaka R, Yamada T. Tandyukisins E and F, novel cytotoxic decalin derivatives isolated from a marine sponge-derived fungus. Tetrahedron Lett. 2016;57:5070–3.
98. Yu J-Y, Shi T, Zhou Y, Xu Y, Zhao D-L, Wang C-Y. Naphthalene derivatives and halogenate quinoline from the coral-derived fungus Trichoderma harzianum (XS-20090075) through OSMAC approach. J Asian Nat Prod Res. 2021;23:250–7.
99. Khamthong N, Rukachaisirikul V, Tadpetch K, Kaewpet M, Phongpaichit S, Preedanon S, Sakayaroj J. Tetrahydroanthraquinone and xanthone derivatives from the marine-derived fungus Trichoderma aureoviride PSU-F95. Arch Pharm Res. 2012;35:461–8.
100. Shi T, Hou X-M, Li Z-Y, Cao F, Zhang Y-H, Yu J-Y, Zhao D-L, Shao C-L, Wang C-Y. Harzianumnones A and B: two hydroxyanthraquinones from the coral-derived fungus Trichoderma harzianum. RSC Adv. 2018;8:27596.
101. Pang X, Lin X, Tian Y, Liang R, Wang J, Yang B, Zhou X, Kaliyaperumal K, Luo X, Tu Z, Liu Y. Three new polyketides from the marine sponge-derived fungus Trichoderma sp. SCSIO41004. Nat Prod Res. 2018;32:105–11.
102. Ohkawa Y, Miki K, Suzuki T, Nishio K, Sugita T, Kinoshita K, Takahashi K, Koyama K. Antiangiogenic metabolites from a marine-derived fungus, Hypocrea vinosa. J Nat Prod. 2010;73:579–82.
103. Shi Z-Z, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Trichorenins A–C, algicidal tetracyclic metabolites from the marine-alga-epiphytic fungus Trichoderma virens Y13–3. J Nat Prod. 2018;81:1121–4.
104. Mereyala HB, Gadikota RR. A concise synthesis of harzialactone A from d-glucose and revision of absolute stereochemistry. Tetrahedron Asym. 1999;10:2305–6.
105. Sun S, Tian L, Wu Z-H, Chen G, Wu H-H, Wang Y-N, Pei Y-H. Two new compounds from fermentation liquid of the marine fungus Trichoderma atroviride G20–12. J Asian Nat Prod Res. 2009;11:898–903.
106. Abdel-Lateff A, Fisch K, Wright AD. Trichopyrone and other constituents from the marine sponge-derived fungus Trichoderma sp. Z Naturforsch. 2009;64c:186–92.
107. Yamazaki H, Rotinsulu H, Narita R, Takahashi R, Namikoshi M. Induced production of halogenated epidithiodiketopiperazines by a marinederived Trichoderma cf. brevicompactum with sodium halides. J Nat Prod. 2015;78:2319–21.
108. Yamazaki H, Takahashi O, Murakami K, Namikoshi M. Induced production of a new unprecedented epitrithiodiketopiperazine, chlorotrithiobrevamide, by a culture of the marine-derived Trichoderma cf. brevicompactum with dimethyl sulfoxide. Tetrahedron Lett. 2015;56:6262–5.
109. Shi Z-Z, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Sulfurated diketopiperazines from an algicolous isolate of Trichoderma virens. Phytochem Lett. 2018;27:101–4.
110. Lu X, Tian L, Chen G, Xu Y, Wang H-F, Li Z-Q, Pei Y-H. Three new compounds from the marine-derived fungus Trichoderma atroviride G20–12. J Asian Nat Prod Res. 2012;14:647–51.
111. Sun Y, Tian L, Huang Y-F, Sha Y, Pei Y-H. A new cyclotetrapeptide from marine fungus Trichoderma reesei. Pharmazie. 2006;61:809–10.
112. Garo E, Starks CM, Jensen PR, Fenical W, Lobkovsky E, Clardy J. Trichodermamides A and B, cytotoxic modified dipeptides from the marinederived fungus Trichoderma virens. J Nat Prod. 2003;66:423–6.
113. Yamazaki H, Rotinsulu H, Takahashi O, Kirikoshi R, Namikoshi M. Induced production of a new dipeptide with a disulfide bridge by long-term fermentation of marine-derived Trichoderma cf. brevicompactum. Tetrahedron Lett. 2016;57:5764–7.
114. Pruksakorn P, Arai M, Kotoku N, Vilchèze C, Baughn AD, Moodley P, Jacobs WR Jr, Kobayashi M. Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria. Bioorg Med Chem Lett. 2010;20:3658–63.
115. Kavianinia I, Kunalingam L, Harris PWR, Cook GM, Brimble MA. Total synthesis and stereochemical revision of the anti-tuberculosis peptaibol trichoderin A. Org Lett. 2016;18:3878–81.
116. Ren J, Xue C, Tian L, Xu M, Chen J, Deng Z, Proksch P, Lin W. Asperelines A–F, peptaibols from the marine-derived fungus Trichoderma asperellum. J Nat Prod. 2009;72:1036–44.
117. Chen L, Zhong P, Pan J-R, Zhou K-J, Huang K, Fang Z-X, Zhang Q-Q. Asperelines G and H, two new peptaibols from the marine-derived fungus Trichoderma asperellum. Heterocycles. 2013;87:645–55.
118. Ren J, Yang Y, Liu D, Chen W, Proksch P, Shao B, Lin W. Sequential determination of new peptaibols asperelines G-Z₁₂ produced by marinederived fungus Trichoderma asperellum using ultrahigh pressure liquid chromatography combined with electrospray-ionization tandem mass spectrometry. J Chromatogr A. 2013;1309:90–5.
119. Mohamed-Benkada M, Montagu M, Biard J-F, Mondeguer F, Verite P, Dalgalarrondo M, Bissett J, Pouchus YF. New short peptaibols from a marine Trichoderma strain. Rapid Commun Mass Spectrom. 2006;20:1176–80.
120. Ruiz N, Wielgosz-Collin G, Poirier L, Grovel O, Petit KE, Mohamed-Benkada M, du Pont TR, Bissett J, Vérité P, Barnathan G, Pouchus YF. New trichobrachins, 11-residue peptaibols from a marine strain of Trichoderma longibrachiatum. Peptides. 2007;28:1351–8.
121. Carroux A, Van Bohemen A-I, Roullier C, du Pont TR, Vansteelandt M, Bondon A, Zalouk-Vergnoux A, Pouchus YF, Ruiz N. Unprecedented 17-residue peptaibiotics produced by marine-derived Trichoderma atroviride. Chem Biodivers. 2013;10:772–86.
122. Panizel I, Yarden O, Ilan M, Carmeli S. Eight new peptaibols from sponge-associated Trichoderma atroviride. Mar Drugs. 2013;11:4937–60.
123. Mohamed-Benkada M, Pouchus YF, Vérité P, Pagniez F, Caroff N, Ruiz N. Identification and biological activities of long-chain peptaibols produced by a marine-derived strain of Trichoderma longibrachiatum. Chem Biodivers. 2016;13:521–30.
124. Touati I, Ruiz N, Thomas O, Druzhinina IS, Atanasova L, Tabbene O, Elkahoui S, Benzekri R, Bouslama L, Pouchus YF, Limam F. Hyporientalin A, an anti-Candida peptaibol from a marine Trichoderma orientale. World J Microbiol Biotechnol. 2018;34:98.
125. Hao M-J, Chen P-N, Li H-J, Wu F, Zhang G-Y, Shao Z-Z, Liu X-P, Ma W-Z, Xu J, Mahmud T, Lan W-J. β-Carboline alkaloids from the deep-sea fungus Trichoderma sp. MCCC 3A01244 as a new type of anti-pulmonary fibrosis agent that inhibits TGF-b/Smad signaling pathway. Front Microbiol. 2022;13:947226.
126. Wu B, Oesker V, Wiese J, Schmaljohann R, Imhoff JF. Two new antibiotic pyridones produced by a marine fungus, Trichoderma sp. strain MF106. Mar Drugs. 2014;12:1208–19.
127. Liu T, Li Z-L, Wang Y, Tian L, Pei Y-H, Hua H-M. A new alkaloid from the marine-derived fungus Hypocrea virens. Nat Prod Res. 2011;25:1596–9.
128. Ni M, Lin Y-N, Deng C-L. A novel alkaloid from the marine-derived fungus Trichoderma citrinoviride. Chin J Mar Drugs. 2020;39:71–6.
129. Ding L-J, Yuan W, Li Y-X, Liao X-J, Sun H, Peng Q, Han B-N, Lin H-W, Li Z-Y, Yang F, Xu S-H. Hypocrol A, a new tyrosol derivative from a sponge-derived strain of the fungus Hypocrea koningii. Nat Prod Res. 2016;30:1633–8.
130. Rehman SU, Wu J-S, Yang L-J, Ting S, Shao C-L, Wang C-Y. One new terphenyl glycoside from a sponge-derived fungus Trichoderma reesei (HN-2016-018). Nat Prod Commun. 2020;15:1–5.
131. Huang H-R, Xia X-K, She Z-G, Lin Y-C, Vrijmoed LLP, Jones EBG. A new chloro-monoterpene from the mangrove endophytic fungus Tryblidiopycnis sp. (4275). J Asian Nat Prod Res. 2006;8:609–12.
132. Ebel R. Terpenes from marine-derived fungi. Mar Drugs. 2010;8:2340–68.
133. Li C-S, Liu L-T, Yang L, Li J, Dong X. Chemistry and bioactivity of marinederived bisabolane sesquiterpenoids: a review. Front Chem. 2022;10: 881767.

[1]	Alejandro Recio-Balsells, Eugenia Rodriguez Ristau, Adriana Pacciaroni, Viviana Nicotra, Carina Casero, Manuela García. Rational search for natural antimicrobial compounds: relevance of sesquiterpene lactones [J]. Natural Products and Bioprospecting, 2025, 15(3): 28-28.
[2]	Wei-Ye Wu, Xun Wei, Qiong Liao, Yi-Fan Fu, Lei-Ming Wu, Lei Li, Shu-Qi Wu, Qing-Ren Lu, Fang-Yu Yuan, Dong Huang, Zhang-Hua Sun, Tao Yuan, Gui-Hua Tang. Structurally diverse polyketides and alkaloids produced by a plant-derived fungus Penicillium canescens L1 [J]. Natural Products and Bioprospecting, 2025, 15(3): 22-22.
[3]	Zhou-Wei Wu, Xue-Fang Zhao, Chen-Xi Quan, Xiao-Cui Liu, Xin-Yu Tao, Yu-jie Li, Xing-Rong Peng, Ming-Hua Qiu. Structure-function insights of natural Ganoderma polysaccharides: advances in biosynthesis and functional food applications [J]. Natural Products and Bioprospecting, 2025, 15(2): 15-15.
[4]	Olusesan Ojo, Idris Njanje, Dele Abdissa, Tarryn Swart, Roxanne L. Higgitt, Rosemary A. Dorrington. Newly isolated terpenoids (covering 2019-2024) from Aspergillus species and their potential for the discovery of novel antimicrobials [J]. Natural Products and Bioprospecting, 2025, 15(2): 19-19.
[5]	Dong-Yang Wang, Ming-Xing Li, Yan-Chao Xu, Peng Fu, Wei-Ming Zhu, Li-Ping Wang. Dibohemamines I-O from Streptomyces sp. GZWMJZ-662, an endophytic actinomycete from the medicinal and edible plant Houttuynia cordata Thunb. [J]. Natural Products and Bioprospecting, 2025, 15(1): 9-9.
[6]	Jiaojiao Ji, Lanlan Zang, Tingting Lu, Cheng Li, Xiaoxu Han, Soo-Rang Lee, Li Wang. Widely targeted metabolomics analysis reveals differences in volatile metabolites among four Angelica species [J]. Natural Products and Bioprospecting, 2025, 15(1): 2-2.
[7]	Ahmed H. Elbanna, Xinhui Kou, Dilip V. Prajapati, Surasree Rakshit, Rebecca A. Butcher. Discovery of a parallel family of euglenatide analogs in Euglena gracilis [J]. Natural Products and Bioprospecting, 2025, 15(1): 10-10.
[8]	Alica Fischle, Mika Lutsch, Florian Hübner, Linda Sch?ker-Hübner, Lina Schürmann, Finn K. Hansen, Svetlana A. Kalinina. Micro-scale screening of genetically modified Fusarium fujikuroi strain extends the apicidin family [J]. Natural Products and Bioprospecting, 2024, 14(6): 51-51.
[9]	Hamid Ahmadpourmir, Homayoun Attar, Javad Asili, Vahid Soheili, Seyedeh Faezeh Taghizadeh, Abolfazl Shakeri. Natural-derived acetophenones: chemistry and pharmacological activities [J]. Natural Products and Bioprospecting, 2024, 14(4): 28-28.
[10]	Ismail Ware, Katrin Franke, Andrej Frolov, Kseniia Bureiko, Elana Kysil, Maizatulakmal Yahayu, Hesham Ali El Enshasy, Ludger A. Wessjohann. Comparative metabolite analysis of Piper sarmentosum organs approached by LC-MS-based metabolic profiling [J]. Natural Products and Bioprospecting, 2024, 14(4): 30-30.
[11]	Antonio Evidente. Advances on anticancer fungal metabolites: sources, chemical and biological activities in the last decade (2012-2023) [J]. Natural Products and Bioprospecting, 2024, 14(4): 31-31.
[12]	Gleb V. Borkunov, Elena V. Leshchenko, Dmitrii V. Berdyshev, Roman S. Popov, Ekaterina A. Chingizova, Nadezhda P. Shlyk, Andrey V. Gerasimenko, Natalya N. Kirichuk, Yuliya V. Khudyakova, Viktoria E. Chausova, Alexandr S. Antonov, Anatoly I. Kalinovsky, Artur R. Chingizov, Ekaterina A. Yurchenko, Marina P. Isaeva, Anton N. Yurchenko. New piperazine derivatives helvamides B-C from the marine-derived fungus Penicillium velutinum ZK-14 uncovered by OSMAC (One Strain Many Compounds) strategy [J]. Natural Products and Bioprospecting, 2024, 14(4): 32-32.
[13]	Jianzhao Qi, Shi-jie Kang, Ling Zhao, Jin-ming Gao, Chengwei Liu. Natural and engineered xylosyl products from microbial source [J]. Natural Products and Bioprospecting, 2024, 14(3): 13-13.
[14]	Zhe-Wei Yu, Bang-Ping Cai, Su-Zhi Xie, Yi Zhang, Wen-Hui Wang, Shun-Zhi Liu, Yan-Lin Bin, Qi Chen, Mei-Juan Fang, Rong Qi, Ming-Yu Li, Ying-Kun Qiu. Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others [J]. Natural Products and Bioprospecting, 2024, 14(3): 23-23.
[15]	Kritika Jalota, Vikas Sharma, Chiti Agarwal, Suruchi Jindal. Eco-friendly approaches to phytochemical production: elicitation and beyond [J]. Natural Products and Bioprospecting, 2024, 14(1): 5-5.