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

凭借这一合作RUI奖，生命过程化学项目资助了由加州保利圣路易斯·奥比斯波的John Marlier教授领导的Emily Fogle教授、Lori Robins教授和Kristen Meisenheimer教授的研究团队，以研究硫酯水解的机理。硫代酯是生物催化中的重要中间体，从脂肪酸的合成到聚酮合成酶的缩合，再到内切和现代化学天然化学连接中的对应物。这一建议旨在更好地了解生物相关硫酯在溶液中和在酶活性部位进行水解的机理。使用的主要工具是动力学同位素效应(Kie)。事实上，这项提议将有助于支持加州保利SLO的一个长期部门努力，以建立一个专题本科生研究计划，专门研究Kie的技术来研究机制。教职员工团队预计将为本科生提供现代物理有机化学的一对一培训，重点关注与生物相关的问题。加州大学保利分校的团队将努力通过将妇女和传统上代表性不足的群体的成员纳入研究企业来扩大对化学的参与。从长远来看，希望通过这些研究，能够对硫酯裂解和缩合反应的机理有一个基本的认识。

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.