- 2:15 PM

Exploring Enzymology for New Industrial Syntheses

Vince Vilker, Office of Testing and Research, FDA, 3203 Cummings Ln, Chevy Chase, MD 20815

In this seminar, I discuss the chemistry, structural and mechanistic features of the enzymes chorismate lyase and cytochrome P450 that make them attractive catalysts for synthesizing important compounds in the fine chemical, pharmaceutical and synthetic materials industries. Chorismate, a key intermediate in the aromatic amino acid metabolic pathway (shikimate pathway) found in all microorganisms and plants, is converted to para-hydroxybenzoate, a valuable monomer for polymer synthesis. There are several competing pathways for chorismate in whole cell production methods, and the direct enzymatic conversion of chorismate would be an attractive alternative process if the product inhibition limitations of the wild-type enzyme could be eliminated. In this presentation, our studies of the functional and structural features of chorismate lyase that lead to this product inhibition are described. The cytochrome P450 family of enzymes is well studied because of their importance in many physiological biotransformations such as hormone synthesis, pro-drug activation, and clearance of xenobiotic compounds. The products of P450 activity are often compounds that have been hydroxylated with high regio- and stereo-specificity. This presentation describes our studies to characterize patterns of hydroxylation for products made by the P450 catalyzed conversion of styrene, benzocycloarenes, and halocarbons. I also describe our spectroscopic and electrochemical measurements to understand the multi-protein associations required to bring about P450 catalytic reactions, and our innovations to bypass some of the limitations that arise from the need for these associations when adapting the exquisite synthesis potential of these enzyme systems to industrial biotransformations.