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

RUI：硫酯水解：自然界最具反应性的酰基之一的机理研究

• 批准号: 1049689
• 负责人: John Marlier
• 金额: $ 21.49万
• 依托单位: California Polytechnic State University Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1049689&HistoricalAwards=false
• 关键词: RUI; Thioester; hydrolysis; mechanistic; study

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.

凭借这一 RUI 合作奖，生命过程化学项目正在资助 Emily Fogle、Lori Robins 和 Kristen Meisenheimer 教授的研究团队，在 John Marlier 教授的领导下，他们都来自加州理工大学圣路易斯奥比斯波分校，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，再到内含肽自切片及其在现代化学天然化学连接中的对应物。 该提案旨在更好地了解生物学相关硫酯在溶液中和酶活性位点中进行水解的机制。 使用的主要工具是动力同位素效应（KIE）。事实上，这一提案将有助于加强加州理工学院 SLO 的常设部门工作，以建立一个专题本科生研究项目，专门研究 KIE 技术来研究机制。教师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，重点关注生物学相关问题。 加州理工学院团队将努力通过将女性和传统上代表性不足的群体成员纳入研究事业来扩大对化学的参与。 从长远来看，希望通过这些研究获得关于硫酯裂解和缩合反应机制的基本见解。