Benzalacetone synthase (BAS) is a plant-specific chalcone synthase (CHS) superfamily type III poyketide synthase (PKS) that catalyzes a one-step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA. The diketide forming activity of Rheum palmatum BAS is attributed to the characteristic substitution of the conserved active-site Phe215 with Leu (numbering in Medicago sativa CHS). To further understand the intimate three-dimensional structural details of the enzyme catalyzed processes, we carried out X-ray crystallographic analyses of R. palmatum BAS. The crystal structures solved at 1.6Å and 1.8Å resolution suggested that, unlike M. sativa CHS, R. palmatum BAS utilizes an alternative active-site pocket to lock the aromatic moiety of the coumaroyl starter for the diketide formation reaction. These results provided structural insights into the functional diversity of type III PKS superfamily enzymes, and suggest strategies for the engineered biosynthesis of plant polyketides.
