The status of type I polyketide synthase ketoreductases

Abstract

Complex polyketides are a large group of structurally diverse and pharmaceutically important natural products known for their multiple chiral centers harboring hydroxyl and alkyl substituents. Numerous studies to decipher how stereochemistry is controlled during their biosyntheses have determined that ketoreductases usually set most of their chiral centers. While the reliable engineering of ketoreductases within modular polyketide synthases to set new stereocenters in complex polyketides has yet to be realized, this review summarizes the contributions of biochemical studies, engineering efforts, and structural biology to understanding these stereocenter-molding enzymes.