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

与此合作RUI奖，生命过程的化学计划资助教授艾米丽Festival，洛里罗宾斯和克里斯汀Meisenheimer的研究团队，在教授约翰·马里耶的领导下，所有的加州理工圣路易斯奥比斯波，研究硫酯水解的机制。 硫酯是生物催化中的重要中间体，从脂肪酸合成到聚酮合酶缩合到内含肽自切割及其在现代化学天然化学连接中的对应物。 该提议旨在更好地理解生物相关的硫酯在溶液和酶活性位点中进行水解的机制。 所采用的主要工具是动力学同位素效应。事实上，这一提议将有助于加强Cal Poly SLO的长期部门努力，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。预计教师团队将为本科生提供现代物理有机化学的一对一培训，重点是生物相关问题。 Cal Poly团队将努力通过将女性和传统上代表性不足的群体成员融入研究企业来扩大化学的参与。 从长远来看，人们希望通过这些研究获得关于硫酯裂解和缩合反应机理的基本见解。

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.