Collaborative Research: Understanding and exploiting the structure-function link between fatty acid biosynthesis and degradation enzymes for functionalized small molecule synthesis

合作研究：了解和利用脂肪酸生物合成和功能化小分子合成的降解酶之间的结构功能联系

• 批准号: 1805510
• 负责人: Justin Siegel
• 金额: $ 30.14万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1805510&HistoricalAwards=false
• 关键词: Collaborative; Research; Understanding; exploiting; structure

Commercially important products are often built up from small molecules. Bacteria and other microbes are proficient at producing such molecules. Many are synthesized from fats and fatty acids. Understanding how the cells make and modify fats will help determine how to make renewable fuels and chemicals in large amounts using microbes. The project will also help educate our society in the challenges and opportunities on the road to a sustainable future. This includes advising and training of undergraduate and high school students from school districts serving predominantly minority populations. Together, these efforts will provide academic and industrial training in areas of strategic national importance.Insight into the evolutionary divergence of fatty acid biosynthesis (FAB) and beta-oxidation (BOX) pathways will be sought by characterizing enzyme/substrate interactions and the unique characteristics of enzymes from various organisms. Using non-decarboxylative condensation and β-reduction reactions, molecules with novel functionalities will be generated. Type II FAB and BOX enzymes will be used interchangeably to capitalize on the advantageous characteristics of each set of enzymes. An integrated approach in which computational protein modeling and design will guide experimentation through molecular modeling of the FAB and BOX enzymes with a wide array of biosynthetically accessible compounds will be undertaken. The specific objectives of the project are: 1) computational protein modeling and design of type II FAB and BOX enzymes; 2) in vitro characterization of type II FAB and BOX enzymes; and 3) in vivo construction and characterization of combinations of type II FAB and BOX enzymes. Medium chain (C5-C8) dicarboxylic and methyl-branched carboxylic acids, specifically dicarboxylates adipic (C6) and suberic (C8) acids and methyl-branched unsaturated tiglic acid (C5) will be produced.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

商业上重要的产品通常是由小分子制成的。细菌和其他微生物擅长产生此类分子。许多是由脂肪和脂肪酸合成的。了解细胞如何制造和修饰脂肪将有助于确定如何利用微生物大量制造可再生燃料和化学品。该项目还将帮助我们的社会了解通向可持续未来的挑战和机遇。这包括为主要服务于少数族裔的学区的本科生和高中生提供建议和培训。这些努力将共同为具有国家战略意义的领域提供学术和工业培训。通过表征酶/底物相互作用和独特特征，深入了解脂肪酸生物合成（FAB）和β-氧化（BOX）途径的进化差异来自各种生物体的酶。使用非脱羧缩合和还原反应，将产生具有新功能的分子。 II 型 FAB 和 BOX 酶将互换使用，以充分利用每组酶的优势特性。将采用一种综合方法，其中计算蛋白质建模和设计将通过 FAB 和 BOX 酶的分子建模以及多种可生物合成的化合物来指导实验。该项目的具体目标是：1）计算蛋白质模型和II型FAB和BOX酶的设计； 2) II型FAB和BOX酶的体外表征； 3) II 型 FAB 和 BOX 酶组合的体内构建和表征。将生产中链 (C5-C8) 二羧酸和甲基支链羧酸，特别是己二酸 (C6) 和辛二酸 (C8) 酸以及甲基支链不饱和 Tigglic 酸 (C5)。该奖项反映了 NSF 的法定使命，并已被通过使用基金会的智力优点和更广泛的影响审查标准进行评估，认为值得支持。