Biosynthetic diversification of peptaibol mediates fungus-mycohost interactions

Fungi have evolved a plethora of functionally diverse secondary metabolites (SMs) to enhance their adaptation to various environments. To understand how structurally diverse metabolites contribute to fungal adaptation, we elucidate fungus-mycohost specific interactions mediated by a family of polypeptides, i.e., peptaibols. We specified that peptaibol structural diversification was attributed to the nonspecific substrate recognition by the highly conserved peptaibol synthetases (PSs) in dead wood inhabiting mycoparasitic fungi from the genus Trichoderma. Exemplified by investigation of T. hypoxylon, we characterized a library of 19 amino acid residue peptaibols, named trichohypolins, containing 42 derivatives synthesized by a single PS enzyme (NPS1Th). Elimination of trichohypolin production by the deletion of nps1Th reduced the inhibitory activities of T. hypoxylon on at least 15 saprotrophic host fungi, indicating that peptaibols are essential for interactions of Trichoderma spp. with their mycohosts. Different antagonistic effects of five trichohypolin subfractions SF1–SF5 and two pure compounds trichohypolins A (1) and B (2) on saprotrophic host fungi revealed specific activities of peptaibol derivatives in mediating fungus-mycohost interaction. Our study provides insights into the role of metabolic diversity of biosynthetic pathways in interfungal interactions.