RUI: Interdisciplinary Collaboration to Expand Asymmetric Synthesis through Biocatalysis

RUI：跨学科合作通过生物催化扩大不对称合成

• 批准号: 0848708
• 负责人: Brent Feske
• 金额: $ 19.54万
• 依托单位: ARMSTRONG STATE UNIVERSITY
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0848708&HistoricalAwards=false
• 关键词: RUI; Interdisciplinary; Collaboration; Expand; Asymmetric

The overall goal of this project is to expand asymmetric synthesis techniques through biocatalysis. It includes three specific aims. Specific aim 1 involves the screening of a variety of prochiral substrates (ketones and oximes) against a library of engineered E. coli yeast reductases that have been characterized as excellent asymmetric reducing agents. Specific aim 2 involves the molecular modeling studies of 2,5-Diketo-D-gluconic acid reductase. In this reductase, the enzyme substrate interaction and its correlation with Si or Re face hydride transfer will be investigated. In specific aim 3, representative yeast reductases will be systematically mutated and the effects on the asymmetric reduction on known substrates will be determined. The goal of this aim is to attain a more accurate understanding of the enzyme-substrate complex and its role in determining enzyme stereoselectivity with the intention of improving asymmetric catalysts.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Brent Feske (Department of Chemistry and Physics), Professor Clifford Padgett (Department of Chemistry and Physics), and Professor Scott Mateer (Department of Biology) at Armstrong Atlantic State University. The combined research of these professors will investigate the use of enzymes to synthesize complex molecules with asymmetric centers. Successful development of this methodology will afford greener and more efficient routes to these molecules, which are needed in large numbers in the pharmaceutical industry.

该项目的总体目标是通过生物催化扩展不对称合成技术。 它包括三个具体目标。 具体目标1涉及针对工程化的大肠杆菌文库筛选各种前手性底物（酮和肟）。大肠杆菌酵母还原酶已被表征为优异的不对称还原剂。 具体目标2涉及2，5-二酮-D-葡萄糖酸还原酶的分子模拟研究。 在这种还原酶中，酶底物相互作用及其与Si或Re面氢化物转移的相关性将被研究。 在具体目标3中，将系统地突变代表性酵母还原酶，并确定对已知底物的不对称还原的影响。 该项目的目标是更准确地了解酶-底物复合物及其在确定酶立体选择性方面的作用，以改进不对称催化剂。有了这个奖项，有机和大分子化学项目支持了布伦特费斯克教授的研究（化学和物理系），Clifford Padgett教授（化学和物理系），以及阿姆斯特朗大西洋州立大学的Scott Mateer教授（生物系）。 这些教授的联合研究将研究使用酶来合成具有不对称中心的复杂分子。 这种方法的成功开发将为制药行业大量需要的这些分子提供更绿色和更有效的途径。