Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization.

ABSTRACT: Tropinone is the first intermediate in the biosynthesis of the pharmacologically important tropane alkaloids that possesses the 8-azabicyclo[3.2.1]octane core bicyclic structure that defines this alkaloid class. Chemical synthesis of tropinone was achieved in 1901 but the mechanism of tropinone biosynthesis has remained elusive. In this study, we identify a root-expressed type III polyketide synthase from Atropa belladonna (AbPYKS) that catalyzes the formation of 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This catalysis proceeds through a non-canonical mechanism that directly utilizes an unconjugated N-methyl-Δ¹-pyrrolinium cation as the starter substrate for two rounds of malonyl-Coenzyme A mediated decarboxylative condensation. Subsequent formation of tropinone from 4-(1-

SUBMITTER: Bedewitz MA 

PROVIDER: S-EPMC6290073 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature