Polyketide Decarboxylative Chain Termination Preceded by O-Sulfonation in Curacin A Biosynthesis

摘要

Curacin A (Figure 1A), a marine cyanobacterial metabolite isolated from marine cyanobacterium Lyngbya majuscula, is a mixed-polyketide nonribosomal-peptide natural product with potent anticancer activities.The biosynthetic pathway generates a series of intermediates with increasing hydrophobicity leading to the final product.Accordingly, several types of decarboxylases have been identified to catalyze the release of 11 CO_2 molecules during curacin A biosynthesis.In addition, polar functional groups formed in the chain elongation intermediates (e.g., keto and hydroxyl groups) are eliminated by the coupled β-keto reduction/β-hydroxyl dehydration, HMG polyketide β-branching, and cyclopropanation reactions, with the only remaining hydroxyl group modified as the methyl ether derivative. Moreover, as a linear polyketide, curacin A contains an unusual hydrophobic terminal olefin instead of a typical terminal carboxyl, aldehyde, or alcohol group.