RUI: Thioester hydrolysis: A mechanistic study of one of nature's most reactive acyl groups

California Polytechnic State University Foundation, San Luis Obispo CA

Investigators

Abstract

With this collaborative RUI award, the Chemistry of Life Processes program is funding the research team of Professors Emily Fogle, Lori Robins and Kristen Meisenheimer, under the leadership of Professor John Marlier, all of Cal Poly San Luis Obispo, to study the mechanism of thioester hydrolysis. Thioesters are important intermediates in biological catalysis from fatty acid synthesis, to polyketide synthase condensations to intein self-slicing and its counterpart in modern chemical native chemical ligation. This proposal seeks to better understand the mechanism by which biologically relevant thioesters undergo hydrolysis, both in solution and in an enzyme active site. The principal tool to be employed is that of kinetic isotope effects (KIEs). Indeed, this proposal will help to bolster a standing departmental effort at Cal Poly SLO to build a thematic undergraduate research program that specializes in the techniques of KIEs to study mechanism. The faculty team is expected to provide one-on-one training to undergraduates in modern physical organic chemistry with a focus on a biologically relevant problem. The Cal Poly team will strive to broaden participation in chemistry through the integration of women and members of traditionally underrepresented groups into the research enterprise. In the longer term, it is hoped that fundamental insights on the mechanism of thioester cleavage and condensation reactions will be obtained through these studies.