Discovery and Characterization of a PKS–NRPS Hybrid in Aspergillus terreus by Genome Mining

Fungal polyketide synthase–nonribosomal peptide synthetase (PKS–NRPS) hybrids have been characterized to produce polyketide–amino acid compounds with striking structural features and biological activities. In this study, a PKS–NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS–NRPS gene cluster was successfully activated and ten products (1–10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS–NRPS hybrid identified in A. terreus.