A fungal nonribosomal peptide-polyketide hybrid synthase synthesizes 2-pyrrolidinone alkaloid

A new fungal nonribosomal peptide-polyketide hybrid synthase , namely CogA, was discovered by genome mining from fungus Cordyceps gunnii . Its ability to synthesize 4-hydroxyl 2-pyrrolidinone alkaloid ( 1 ) via nonenzyme-catalyzed N-1-C-2 closure was confirmed by heterologous expression of it in Aspergillus nidulans . Further engineered biosynthesis of the fluoro-substituted 2-pyrrolidinone alkaloid analogues ( 4 and 5 ) has also been achieved in vivo .