Improving Alkene Reductases for Applications in Asymmetric Synthesis

改进烯烃还原酶在不对称合成中的应用

• 批准号: 1111791
• 负责人: Jon Stewart
• 金额: $ 45万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1111791&HistoricalAwards=false
• 关键词: Improving; Alkene; Reductases; Applications; Asymmetric

With this award, the Chemical Synthesis program is supporting Professor Jon D. Stewart of the Department of Chemistry at the University of Florida to develop new enzyme catalysts for asymmetric conjugated alkene reductions. To date, the overall impact of these enzymes on synthetic chemistry has been modest because the wild-type enzymes accept only a limited range of substrates, provide one possible stereoisomer and lack long-term stability. To overcome these problems, existing flavin-dependent reductase enzymes will be systematically varied at amino acid positions rated most likely to yield improved mutants. X-ray crystallography will be used to understand how substrates bind in the active sites of improved enzymes.The broader impacts involve mentoring high school students (U.F. Precollegiate Training Program), undergraduates (NSF REU), graduate students and postdoctoral researchers, including members of historically underrepresented groups in chemistry. Moreover, the work will provide diverse training in chemistry, x-ray crystallography, molecular biology and biochemistry to these coworkers. In terms of scientific broader impacts, this work is directed at efficient, environmentally benign methods for producing chiral building blocks for medicinal, agrochemical and industrial chemical applications. In addition, the insights gleaned from combining protein engineering, structural studies and catalytic assays will provide new information on flavoproteins, an important class of biocatalysts involved in a diverse set of reactions at the chemistry/biology interface.

凭借该奖项，化学合成项目将支持佛罗里达大学化学系的 Jon D. Stewart 教授开发用于不对称共轭烯烃还原的新型酶催化剂。 迄今为止，这些酶对合成化学的总体影响不大，因为野生型酶仅接受有限范围的底物，提供一种可能的立体异构体并且缺乏长期稳定性。 为了克服这些问题，现有的黄素依赖性还原酶将在最有可能产生改良突变体的氨基酸位置上进行系统改变。 X 射线晶体学将用于了解底物如何与改良酶的活性位点结合。更广泛的影响包括指导高中生（佛罗里达大学预科培训计划）、本科生（NSF REU）、研究生和博士后研究人员，包括化学领域历史上代表性不足的群体的成员。 此外，这项工作将为这些同事提供化学、X射线晶体学、分子生物学和生物化学方面的多样化培训。 就更广泛的科学影响而言，这项工作旨在寻找高效、环境友好的方法来生产用于医药、农用化学品和工业化学品应用的手性结构单元。 此外，通过结合蛋白质工程、结构研究和催化测定获得的见解将提供有关黄素蛋白的新信息，黄素蛋白是参与化学/生物学界面上多种反应的一类重要的生物催化剂。