Engineering Carboxylic Acid Reductase for the Biosyntheses of Industrial Chemicals

蛋白质的结构决定了它们的功能。本项目将尝试修改酶的几个结构特征，以获得更多的生产功能和更高的反应速率。这些酶是新发现的，可以非常有效地将生物质转化为有价值的化学产品。该项目还将为学生提供互动研究体验。pi将继续从未被充分代表的少数民族中招募本科生和研究生参与该项目。pi还将通过内布拉斯加州EPSCoR青年科学家计划组装和分发一套教育工具包，从高中阶段开始，扩展到中学阶段。这将为这些学生提供设计和创造不同蛋白质的实践经验。提出的工作重点是羧酸还原酶（CARs）的研究和工程。该项目的目标是扩大CARs的底物特异性，以便有效地将短链羧酸代谢物还原为醛类。它们作为常见和通用的生物合成中间体，很容易进一步转化为烷烃、烯烃、醇或胺。该建议专门针对CAR突变体，其功能是减少三种丰富的羧酸代谢物，包括D-和l -乳酸（C3底物）和乙醇酸（二碳底物）。进一步还原醛产物可生成R-或s -1,2-丙二醇和乙二醇，这是具有广泛应用的大宗工业化学品，特别是在聚酯生产中。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The structure of proteins determines their function. This project will attempt to modify several structural features of enzymes in order to obtain more productive functions and higher reaction rates. The enzymes are newly discovered and could help convert biomass into valuable chemical products very efficiently. The project will also provide interactive research experiences to students. The PIs will continue recruiting undergraduate and graduate students from underrepresented minorities to work on this project. The PIs will also be assembling and distributing an educational kit through the Nebraska EPSCoR Young Scientists Program, beginning with the HS level and expanding to the middle school level. This will provide these students with hands-on experience designing and creating different proteins.The proposed work focuses on the study and engineering of carboxylic acid reductases (CARs). The goal of the project is to expand the substrate specificity of CARs in order to efficiently reduce short-chain carboxylic acid metabolites into aldehydes. These serve as common and versatile biosynthetic intermediates that are readily to be further converted to alkanes, alkenes, alcohols, or amines. This proposal specifically targets CAR mutants that function on the reduction of three abundant carboxylic acid metabolites, including D- and L-lactic acids (C3 substrates), and glycolic acid (a two-carbon substrate). Further reduction of the aldehyde products leads to the formation of R- or S-1,2- propanediol and ethylene glycol, which are bulk industrial chemicals with broad applications, especially in the production of polyesters.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.