In the April 8, 2008 issue of the Proceedings of National Academy of Sciences, Prof. Sheryl Tsai and coworkers report the crystal structure and chemical biology of the aromatase/cyclase domain from the aromatic polyketide synthase. Microbes are thought to produce polyketides by first making a long-chain linear polyketone then bending and folding it to produce the polyaromatic molecule. But precisely how they accomplished this feat of origami was a mystery. The UCI researchers showed that the aromatase/cyclase contains a C-shaped cavity perfectly configured for housing a long-chain linear polyketone, and the pocket shape is key to the highly specific first and second ring cyclizations. By subtly changing aspects of the active site they will be able to control the size and shape of the polyketide, resulting in the formation of new drugs.
Sunday, April 6, 2008