Characterization of an Exceptional Fungal Mutant Enables the Discovery of the Specific Regulator of a Silent PKS–NRPS Hybrid Biosynthetic Pathway

Filamentous fungi produce a great variety of bioactive secondary metabolites essential for their biotic interactions. Here, we characterized an exceptional Trichoderma mutant overproducing harzianic acids (HAs) with exclusively highly antifungal activity against numerous fungi from different ecological groups. Interestingly, two transcription factors (TFs) were identified in this HA biosynthetic gene cluster (hac BGC), with HacI regulating the biosynthetic genes and HacF being likely responsible for the product transportation essential for the self-detoxification of the fungus from the produced HAs. Evolutionary analysis suggested that the sparse distribution of hac BGC in many environmental opportunistic fungi including several species from Trichoderma, Penicillium, and Aspergillus could result from lateral gene transfers and pervasive gene losses in different lineages of Pezizomycotina. Taken together, we propose that the production of HAs by fungi is to inhibit the growth of the surrounding partners to secure an exclusive position in a competitive community.