Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211

doi:10.1007/s13659-026-00634-y

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (5): 72-72.DOI: 10.1007/s13659-026-00634-y

• ORIGINAL ARTICLES • Previous Articles Next Articles

Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211

Minh Van Nguyen¹, Yeong Seok Kim¹, Seung Mok Ryu², Jaeyoung Kwon³, Hun Kim^1,4, Gyung Ja Choi^1,4, Jae Woo Han^1,4

1. Eco-Friendly New Materials Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea;
2. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju, 58245, Republic of Korea;
3. KIST Gangneung Institute of Natural Products, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea;
4. Department of Medicinal Chemistry and Pharmacology, University Science and Technology, Daejeon, 34113, Republic of Korea

Received:2026-03-19 Accepted:2026-04-19 Online:2026-10-08
Supported by:
The Cooperative Research Program for Agriculture Science and Technology Development of Rural Development Administration of Korea, RS-2024-00341073, Intramural Funding Program of the Korea Research Institute of Chemical Technology, KK2632-20 and BSK26-114.

Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211

Minh Van Nguyen¹, Yeong Seok Kim¹, Seung Mok Ryu², Jaeyoung Kwon³, Hun Kim^1,4, Gyung Ja Choi^1,4, Jae Woo Han^1,4

1. Eco-Friendly New Materials Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea;
2. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju, 58245, Republic of Korea;
3. KIST Gangneung Institute of Natural Products, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea;
4. Department of Medicinal Chemistry and Pharmacology, University Science and Technology, Daejeon, 34113, Republic of Korea

通讯作者: Gyung Ja Choi,E-mail:kjchoi@krict.re.kr;Jae Woo Han,E-mail:jaewoo82@krict.re.kr
基金资助:
The Cooperative Research Program for Agriculture Science and Technology Development of Rural Development Administration of Korea, RS-2024-00341073, Intramural Funding Program of the Korea Research Institute of Chemical Technology, KK2632-20 and BSK26-114.

Abstract

Abstract: In the search for natural products with potent activity against plant diseases, we employed the one strain-many compounds (OSMAC) strategy to the marine-derived fungus Trichoderma virens B211 by supplementing cultures with halogen salts such as sodium bromide (NaBr). Both solid and liquid cultures grown under NaBr-supplemented conditions exhibited markedly darker pigmentation of B211, a diversified secondary metabolite profile, and enhanced antibacterial activity against Erwinia amylovora. Bioassay-guided fractionation of these extracts led to the isolation of fourteen compounds (1-14), including two new polycyclic aromatic terpenoids (1 and 5) belonging to the viridin family. In vitro antimicrobial assays demonstrated that viridin (3) and β-viridin (4), together with gliotoxin (8), displayed broad-spectrum activity against diverse plant pathogenic fungi and bacteria. Notably, viridin derivatives 1 and 2, which are structural isomers, exhibited distinct bioactivity profiles: compound 1 exhibited antifungal activity, whereas compound 2 showed antibacterial activity. Among the isolated metabolites, only gliotoxin (8) and bisdethiobis(methylthio)gliotoxin (9) exhibited direct antibacterial activity against E. amylovora. Furthermore, NaBr-induced crude extracts in which compounds 8 and 9 were the major constituents, as well as the purified compounds themselves, effectively suppressed fire blight symptoms. Collectively, these findings highlight the effectiveness of the OSMAC approach in expanding the chemical diversity of metabolites produced by T. virens B211 and enhancing its potential as a biocontrol agent for plant disease management.

Key words: OSMAC strategy, Marine-derived fungus, Trichoderma virens, Secondary metabolites, Viridin derivatives, Gliotoxin derivatives, Plant disease control

摘要： In the search for natural products with potent activity against plant diseases, we employed the one strain-many compounds (OSMAC) strategy to the marine-derived fungus Trichoderma virens B211 by supplementing cultures with halogen salts such as sodium bromide (NaBr). Both solid and liquid cultures grown under NaBr-supplemented conditions exhibited markedly darker pigmentation of B211, a diversified secondary metabolite profile, and enhanced antibacterial activity against Erwinia amylovora. Bioassay-guided fractionation of these extracts led to the isolation of fourteen compounds (1-14), including two new polycyclic aromatic terpenoids (1 and 5) belonging to the viridin family. In vitro antimicrobial assays demonstrated that viridin (3) and β-viridin (4), together with gliotoxin (8), displayed broad-spectrum activity against diverse plant pathogenic fungi and bacteria. Notably, viridin derivatives 1 and 2 , which are structural isomers, exhibited distinct bioactivity profiles: compound 1 exhibited antifungal activity, whereas compound 2 showed antibacterial activity. Among the isolated metabolites, only gliotoxin (8) and bisdethiobis(methylthio)gliotoxin (9) exhibited direct antibacterial activity against E. amylovora. Furthermore, NaBr-induced crude extracts in which compounds 8 and 9 were the major constituents, as well as the purified compounds themselves, effectively suppressed fire blight symptoms. Collectively, these findings highlight the effectiveness of the OSMAC approach in expanding the chemical diversity of metabolites produced by T. virens B211 and enhancing its potential as a biocontrol agent for plant disease management.

关键词: OSMAC strategy, Marine-derived fungus, Trichoderma virens, Secondary metabolites, Viridin derivatives, Gliotoxin derivatives, Plant disease control

Minh Van Nguyen, Yeong Seok Kim, Seung Mok Ryu, Jaeyoung Kwon, Hun Kim, Gyung Ja Choi, Jae Woo Han. Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211[J]. Natural Products and Bioprospecting, 2026, 16(5): 72-72.

References

[1] Singh BK, Delgado-Baquerizo M, Egidi E, Guirado E, Leach JE, Liu H, et al. Climate change impacts on plant pathogens, food security and paths forward. Nat Rev Microbiol. 2023;21(10):640–56.
[2] Batuman O, Britt-Ugartemendia K, Kunwar S, Yilmaz S, Fessler L, Redondo A, et al. The use and impact of antibiotics in plant agriculture: a review. Phytopathology. 2024;114(5):885–909.
[3] Hobson C, Chan AN, Wright GD. The antibiotic resistome: a guide for the discovery of natural products as antimicrobial agents. Chem Rev. 2022;121(6):3464–94.
[4] Newman DJ. Natural products and drug discovery. Natl Sci Rev. 2022;9:nwac206.
[5] Carroll AR, Copp BR, Grkovic T, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2025;42(2):257–97.
[6] Qi L, Du HF, Sun TT, Li L, Zhang YH, Liu YF, et al. Natural products from marine fungi as a source against agricultural pathogenic fungi. Appl Microbiol Biotechnol. 2023;107(16):5003–17.
[7] Ghazanfar MU, Raza M, Raza W, Qamar MI. Trichoderma as potential biocontrol agent, its exploitation in agriculture: a review. Plant Prot. 2018;2(3):109–35.
[8] Modrzewska M, Bry?a M, Kanabus J, Pierzgalski A. Trichoderma as a biostimulator and biocontrol agent against Fusarium in the production of cereal crops: opportunities and possibilities. Plant Pathol. 2022;71(7):1471–85.
[9] Reino JL, Guerrero RF, Hernandez-Galan R, Collado IG. Secondary metabolites from species of the biocontrol agent Trichoderma. Phytochem Rev. 2008;7(1):89–123.
[10] Howell CR. Understanding the mechanisms employed by Trichoderma virens to effect biological control of cotton diseases. Phytopathology. 2006;96(2):178–80.
[11] Song YP, Ji NY. Chemistry and biology of marine-derived Trichoderma metabolites. Nat Prod Bioprospect. 2024;14(1):14.
[12] Kempken F. Marine fungi: a treasure trove of novel natural products and for biological discovery. PLoS Pathog. 2023;19(9):e1011624.
[13] Li YJ, Qiu MH, Peng XR. Revolutionizing microbial treasure troves: innovative strategies for natural products discovery. Nat Prod Bioprospect. 2026;16(1):12.
[14] Chen Y, Yang W, Zou G, Wang G, Kang W, Yuan J, et al. Cytotoxic bromine-and iodine-containing cytochalasins produced by the mangrove endophytic fungus Phomopsis sp. QYM-13 using the OSMAC approach. J Nat Prod. 2022;85(5):1229–38.
[15] Pinedo-Rivilla C, Aleu J, Durán-Patrón R. Cryptic metabolites from marine-derived microorganisms using OSMAC and epigenetic approaches. Mar Drugs. 2022;20(2):84.
[16] Sharma A, Abrahamian P, Carvalho R, Choudhary M, Paret ML, Vallad GE, et al. Future of bacterial disease management in crop production. Ann Rev Phytopathol. 2022;60(1):259–82.
[17] Ham H, Oh GR, Lee BW, Lee YH, Lee YH. Changes of sensitivity to streptomycin in Erwinia amylovora isolated from 2019 to 2023 in Korea. Res Plant Dis. 2024;30(2):199–205.
[18] Sundin GW, Peng J, Brown LW, Zeng Q, F?rster H, Adaskaveg JE. A novel IncX plasmid mediates high-level oxytetracycline and streptomycin resistance in Erwinia amylovora from commercial pear orchards in California. Phytopathology. 2023;113(12):2165–73.
[19] Park I, Park K, Lee HS, Hong SM, Sriramulu DK, Hwang H, et al. Ecdysteroids from the Korean endemic species Ajuga spectabilis with activities against glucocorticoid receptors and 11β-hydroxysteroid dehydrogenase type 1. ACS Omega. 2023;8(29):26191–200.
[20] Ryu SM, Nam HH, Kim JS, Song JH, Seo YH, Kim HS, et al. Chemical constituents of the egg cases of Tenodera angustipennis (Mantidis ootheca) with intracellular reactive oxygen species scavenging activity. Biomolecules. 2021;11(4):556.
[21] Zhao Q, Chen GD, Feng XL, Yu Y, He RR, Li XX, et al. Nodulisporiviridins A–H, bioactive viridins from Nodulisporium sp. J Nat Prod. 2015;78(6):1221–30.
[22] Ayent AG, Hanson JR, Truneh A. Metabolites of Gliocladium flavofuscumj. Phytochemistry. 1992;32(1):197–8.
[23] Andersson PF, Bengtsson S, Stenlid J, Broberg A. B-norsteroids from Hymenoscyphus pseudoalbidus. Molecules. 2012;17(7):7769–81.
[24] Cao S, Ross L, Tamayo G, Clardy J. Asterogynins: secondary metabolites from a Costa Rican endophytic fungus. Org Lett. 2010;12(20):4661–3.
[25] Svahn KS, G?ransson U, Chryssanthou E, Olsen B, Sj?lin J, Str?mstedt AA. Induction of gliotoxin secretion in Aspergillus fumigatus by bacteria-associated molecules. PLoS ONE. 2014;9(4):e93685.
[26] Kirby GW, Robins DJ, Sefton MA, Talekar RR. Biosynthesis of bisdethiobis(methylthio)gliotoxin, a new metabolite of Gliocladium deliquescens. J Chem Soc Perkin Trans. 1980;1:119–21.
[27] Forseth RR, Fox EM, Chung D, Howlett BJ, Keller NP, Schroeder FC. Identification of cryptic products of the gliotoxin gene cluster using NMR-based comparative metabolomics and a model for gliotoxin biosynthesis. J Am Chem Soc. 2011;133(25):9678–81.
[28] Lee M, Cho JY, Lee YG, Lee HJ, Lim SI, Lee SY, et al. Furan, phenolic, and heptelidic acid derivatives produced by Aspergillus oryzae. Food Sci Biotechnol. 2016;25(5):1259–64.
[29] Koning NR, Strand D. AC–H activation approach to the tricyclic core of glionitrin A and B. ACS Omega. 2022;7(14):12329–41.
[30] Yan S, Li S, Wu W, Zhao F, Bao L, Ding R, et al. Terpenoid and phenolic metabolites from the fungus Xylaria sp. associated with termite nests. Chem Biodivers. 2011;8(9):1689–700.
[31] Kamisuki S, Ishimaru C, Onoda K, Kuriyama I, Ida N, Sugawara F, et al. Nodulisporol and nodulisporone, novel specific inhibitors of human DNA polymerase λ from a fungus. Nodulisporium sp Bioorg Med Chem. 2007;15(9):3109–14.
[32] Hebra T, Pollet N, Touboul D, Eparvier V. Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi. Sci Rep. 2022;12(1):17310.
[33] Hemphill CFP, Sureechatchaiyan P, Kassack MU, Orfali RS, Lin W, Daletos G, et al. OSMAC approach leads to new fusarielin metabolites from Fusarium tricinctum. J Antibiot. 2017;70(6):726–32.
[34] ?zkaya FC, Ebrahim W, El-Neketi M, Tanr?kul TT, Kalscheuer R, Müller WE, et al. Induction of new metabolites from sponge-associated fungus Aspergillus carneus by OSMAC approach. Fitoterapia. 2018;131:9–14.
[35] Wu J, Wang W, Huang X, Zhou L, He Y, Liu Y, et al. Discovery of new cytotoxic terpenoids from Talaromyces amestolkiae HDN21-0307 through NaBr-supplemented OSMAC strategy. Tetrahedron. 2025;189:135020.
[36] Hanson JR. The viridin family of steroidal antibiotics. Nat Prod Rep. 1995;12(4):381–4.
[37] Bernardo PH, Brasch N, Chai CL, Waring P. A novel redox mechanism for the glutathione-dependent reversible uptake of a fungal toxin in cells. J Biol Chem. 2003;278(47):46549–55.
[38] Scharf DH, Brakhage AA, Mukherjee PK. Gliotoxin–bane or boon? Environ Microbiol. 2016;18(4):1096–109.
[39] Downes SG, Owens RA, Walshe K, Fitzpatrick DA, Dorey A, Jones GW, et al. Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion. Sci Rep. 2023;13(1):16156.
[40] Vasilchenko AS, Gurina EV, Drozdov KA, Vershinin NA, Kravchenko SV, Vasilchenko AV. Exploring the antibacterial action of gliotoxin: Does it induce oxidative stress or protein damage? Biochimie. 2023;214:86–95.
[41] Zaid R, Koren R, Kligun E, Gupta R, Leibman-Markus M, Mukherjee PK, et al. Gliotoxin, an immunosuppressive fungal metabolite, primes plant immunity: evidence from Trichoderma virens-tomato interaction. MBio. 2022;13(4):e00389-e422.
[42] Hua L, Zeng H, He L, Jiang Q, Ye P, Liu Y, et al. Gliotoxin is an important secondary metabolite involved in suppression of Sclerotium rolfsii of Trichoderma virens T23. Phytopathology. 2021;111(10):1720–5.
[43] Cain CC, Lee D, Waldo RH III, Henry AT, Casida EJ Jr, Wani MC, et al. Synergistic antimicrobial activity of metabolites produced by a nonobligate bacterial predator. Antimicrob Agents Chemother. 2003;47(7):2113–7.
[44] Hage-Hülsmann J, Grünberger A, Thies S, Santiago-Schübel B, Klein AS, Pietruszka J, et al. Natural biocide cocktails: combinatorial antibiotic effects of prodigiosin and biosurfactants. PLoS ONE. 2018;13(7):e0200940.
[45] Kim S, Kim HM, Yang JE, Jeong SG, Kim YY, Hwang IM, et al. Biological control of the shot-hole disease in flowering cherry tree using antimicrobial compounds produced by Bacillus velezensis 8–2. Chem Biol Technol Agric. 2024;11(1):87.

Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211

Metabolite diversification via halogen salts enhances biocontrol potential of marine-derived Trichoderma virens B211

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Fajar Fauzi Abdullah, Sabrina Aisyah Putri, Noor Aishah Najihah, Nurlelasari, Wahyu Safriansyah, Khalijah Awang, Unang Supratman. Distribution and bioactivities of tirucallane-type triterpenoids from Meliaceae family [J]. Natural Products and Bioprospecting, 2026, 16(5): 65-65.
[2]	Josefine Lange, Lesley Huymann, Sophie Schwarzkopf, Dilara Balci, Mehdi D. Davari, Arijana Turanovic, Clemens Gotsis, Götz Palfner, Bianka Siewert, Ursula Peintner, Norbert Arnold. Cortinarius mapuveronicae from South America, a chemical and morphological link between European and Australian dermocyboid Cortinarii [J]. Natural Products and Bioprospecting, 2026, 16(2): 22-22.
[3]	Yu-Jie Li, Ming-Hua Qiu, Xing-Rong Peng. Revolutionizing microbial treasure troves: innovative strategies for natural products discovery [J]. Natural Products and Bioprospecting, 2026, 16(1): 12-12.
[4]	Ze-Hong Lin, Han-Wen Shan, Li-Kun Yang, Tian-Tian Sun, Li-Ying He, Hui-Fang Du, Ya-Hui Zhang, Shan Liu, Xu Wang, Du-Qiang Luo, Fei Cao. Chalasoergodimers A-E, heterodimers with multiple polymerization modes from a marine-derived Chaetomium sp. fungus [J]. Natural Products and Bioprospecting, 2025, 15(6): 62-62.
[5]	Luana Layse Camara de Almeida, Sayoane Pessoa Fernandes, Genil Dantas de Oliveira, Marcelly da Silveira Silva, Thalisson Amorim de Souza, Valnês S. Rodrigues-Junior, Samuel Paulo Cibulski. Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks [J]. Natural Products and Bioprospecting, 2025, 15(6): 52-52.
[6]	Ni Wayan Martiningsih, Siska Elisahbet Sinaga, Wahyu Safriansyah, Unang Supratman, Desi Harneti. Nitrogen-containing secondary metabolites from Meliaceae Family and their biological activity: a review [J]. Natural Products and Bioprospecting, 2025, 15(5): 47-47.
[7]	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.
[8]	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.
[9]	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.
[10]	Weiwei Peng, Qi Huang, Xin Ke, Wenxuan Wang, Yan Chen, Zihuan Sang, Chen Chen, Siyu Qin, Yuting Zheng, Haibo Tan, Zhenxing Zou. Koningipyridines A and B, two nitrogen-containing polyketides from the fungus Trichoderma koningiopsis SC-5 [J]. Natural Products and Bioprospecting, 2024, 14(1): 8-8.
[11]	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.
[12]	Li Wu, Ning Yang, Meng Guo, Didi Zhang, Reza A. Ghiladi, Hasan Bayram, Jun Wang. The role of sound stimulation in production of plant secondary metabolites [J]. Natural Products and Bioprospecting, 2023, 13(6): 40-40.
[13]	Fengli Li, Saisai Gu, Sitian Zhang, Shuyuan Mo, Jieru Guo, Zhengxi Hu, Yonghui Zhang. Three new amide derivatives from the fungus Alternaria brassicicola [J]. Natural Products and Bioprospecting, 2023, 13(4): 28-28.
[14]	Ke Ye, Hong-Lian Ai, Ji-Kai Liu. Identification and Bioactivities of Secondary Metabolites Derived from Endophytic Fungi Isolated from Ethnomedicinal Plants of Tujia in Hubei Province: A Review [J]. Natural Products and Bioprospecting, 2021, 11(2): 185-205.
[15]	Rong Chen, Jian-Wei Tang, Xing-Ren Li, Miao Liu, Wen-Ping Ding, Yuan-Fei Zhou, Wei-Guang Wang, Xue Du, Han-Dong Sun, Pema-Tenzin Puno. Secondary Metabolites from the Endophytic Fungus Xylaria sp. Hg1009 [J]. Natural Products and Bioprospecting, 2018, 8(2): 121-129.