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.