Genome mining approach for harnessing the cryptic gene cluster in Alternaria solani: production of PKS–NRPS hybrid metabolite, didymellamide B

Abstract Using a heterologous expression system in Aspergillus oryzae we characterized cryptic biosynthetic genes found in Alternaria solani . This system enabled the isolation of an antifungal metabolite, didymellamide B, which was previously not detected in the extract of the A. solani . The co-production and chemical transformation of didymellamide congeners enabled us to decipher the biosynthetic pathway of didymellamide B as follows: (1) formation of a linear polyketide chain with 3-acyltetramate, (2) oxidative ring expansion to yield a 2-pyridone skeleton, and (3) non-enzymatic endo -selective [4+2] cycloaddition to afford a trans -decalin. These results demonstrate the robustness and reliability of the A. oryzae expression system.