Solanapyrone Synthase, a Possible Diels–Alderase and Iterative Type I Polyketide Synthase Encoded in a Biosynthetic Gene Cluster from Alternaria solani

The solanapyrone biosynthetic gene cluster was cloned from Alternaria solani . It consists of six genes— sol1–6 —coding for a polyketide synthase, an O ‐methyltransferase, a dehydrogenase, a transcription factor, a flavin‐dependent oxidase, and cytochrome P450. The prosolanapyrone synthase (PSS) encoded by sol1 was expressed in Aspergillus oryzae and its product was identified as desmethylprosolanapyrone I ( 8 ). Although PSS is closely related to the PKSs/Diels–Alderases LovB and MlcA of lovastatin and compactin biosynthesis, it did not catalyze cycloaddition. Sol5, encoding a flavin‐dependent oxidase (solanapyrone synthase, SPS), was expressed in Pichia pastoris and purified. The purified recombinant SPS showed activity for the formation of (−)‐solanapyrone A ( 1 ) from achiral prosolanapyrone II ( 2 ), establishing that this single enzyme catalyzes both the oxidation and the subsequent cycloaddition reaction, possibly as a Diels–Alder enzyme.