Involvement\nof a Noncanonical Polyketide Synthase–Nonribosomal\nPeptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl\nOxidase Inhibitor PF1163A

PF1163A (<b>1</b>) is a fungal metabolite that\ninhibits sterol-C4-methyl\noxidase. In this study, we identified the biosynthetic gene cluster\nof <b>1</b> and elucidated its biosynthetic pathway through\nheterologous expression experiments. Polyketide synthase–nonribosomal\nsynthetase hybrid PfaA, which is responsible for the biosynthesis\nof PF1163A, harbors an unusual domain organization with tandem condensation\n(C) domains and a terminal condensation domain. Mutagenesis studies\nsuggest that both C domains are required for the function of PfaA.