Predicting the Nature and Timing of Epimerisation on a Modular Polyketide Synthase

Abstract

When and where? Modular polyketide synthases catalyse the Claisen condensation of simple organic acids with inversion of configuration to give a 2R methyl centre. However, according to Celmer's rules, the ultimate stereochemical configuration of many polyketides requires epimerisation to the 2S isomer. It has been generally believed that the epimerisation is performed by the ketosynthase domains. We challenge this traditional thinking and propose bifunctionality of the ketoreductase domains.