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

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.