Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

PF1163A (1) is a fungal metabolite that inhibits sterol-C4-methyl oxidase. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway through heterologous expression experiments. Polyketide synthase–nonribosomal synthetase hybrid PfaA, which is responsible for the biosynthesis of PF1163A, harbors an unusual domain organization with tandem condensation (C) domains and a terminal condensation domain. Mutagenesis studies suggest that both C domains are required for the function of PfaA.