Polyketide Biosynthesis: Modular Polyketide Synthases

Polyketides constitute a large class of microbial and plant-derived secondary metabolites that displays a vast array of structural diversity. These organic molecules vary in molecular weight, functional group modification, and include linear, polycyclic, and macrocyclic structural forms. Currently, polyketide natural products find clinical use as antibiotics, antiparasitic agents, antifungals, anticancer drugs, and immunosuppressants. Given these impressive and wide-ranging pharmacologic activities, an ever-increasing demand is placed on natural products research to uncover novel polyketide metabolites for the benefit of human and animal health. Modular polyketide synthases are nature's platform for the expansion of chemical diversity. This review provides new perspectives on important biosynthetic mechanisms that contribute to this variety. This includes control of double-bond configuration and regiochemistry, introduction of β-branching during polyketide chain assembly, and other processes that contribute to introduction of unique chemical functionality into these fascinating systems.