Structure of chalcone synthase and the molecular basis of plant polyketidebiosynthesis

Chalcone synthase (CHS) is pivotal for the biosynthesis of flavonoid antimi crobial phytoalexins and anthocyanin pigments in plants, It produces chalco ne by condensing one p-coumaroyl- and three malonyl-coenzyme A thioesters i nto a polyketide reaction intermediate that cyclizes, The crystal structure s of CHS alone and complexed with substrate and product analogs reveal the active site architecture that defines the sequence and chemistry of multipl e decarboxylation and condensation reactions and provides a molecular under standing of the cyclization reaction leading to chalcone synthesis, The str ucture of CHS complexed with resveratrol also suggests how stilbene synthas e, a related enzyme, uses the same substrates and an alternate cyclization pathway to form resveratrol, By using the three-dimensional structure and t he large database of CHS-like sequences, we can identify proteins likely to possess novel substrate and product specificity. The structure elucidates the chemical basis of plant polyketide biosynthesis and provides a framewor k for engineering CHS-like enzymes to produce new products.