Structure, Mechanism and Engineering of Polyketide Synthases

Polyketide synthases are a large family of modular megasynthases responsible for the biosynthesis of numerous antibiotics and related pharmacologically active natural products. Over the past decade a variety of studies have demonstrated the feasibility of reprogramming polyketide synthase chemistry by genetic and chemobiosynthetic manipulation. To date most of these efforts have been guided by primary amino acid sequence analysisof polyketide synthases. The growing body of structural data on these enzymes facilitates fundamentally new approaches for biosynthetic engineering. Recent examples of such efforts from the author's laboratory will bepresented.