Grant: Discovery Grants Program - Individual

Plant secondary metabolites such as flavonoids (UV protection), isoflavonoids (Rhizobium nodulation), anthocyanins (floral color), and antimicrobial phytoalexins are all derived from polyketides synthesized by the members of chalcone synthase (CHS) superfamily. These enzymes are small (homodimer of ~42 kDa subunits), yet remarkably complex enzymes and catalyze multiple-step reactions at a single active site. Thus, they provide a good model for other multi-component polyketide synthases, which are responsible for biosynthesis of a variety of useful natural products including antibiotics, immunosuppressants and anticancer agents. Recent structural and mechanistic studies on CHS and related enzymes have yielded insights into enzyme mechanisms and the molecular basis of biosynthetic versatility of the CHS superfamily. Stilbene synthase, another representative member of the superfamily, has attracted much attention in transgenic crop development due to the antifungal activity and a number of beneficial health effects of stilbenes. The proposed mechanistic study on the STS-catalyzed cyclization reaction using unexplored bioorganic chemical approaches will provide much needed insight that should prove valuable in the manipulation of polyketide biosynthesis through metabolic engineering. Already underway are studies on CHS-like enzymes from a cyanobacterium, a nitrogen-fixing bacterium, a moss, and a primitive plant, horsetail. Results obtained from these studies will lead to a better understanding of the evolution of enzyme family and metabolic pathway in plants and microorganisms. Finally, the moss homologue of anther-specific CHSs may provide insights into the poorly understood process of plant male fertility.