Engineering Carboxylic Acid Reductase for the Biosyntheses of Industrial Chemicals

用于工业化学品生物合成的工程羧酸还原酶

• 批准号: 1805528
• 负责人: Wei Niu
• 金额: $ 33.55万
• 依托单位: University of Nebraska-Lincoln
• 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=1805528&HistoricalAwards=false
• 关键词: Engineering; Carboxylic; Acid; Reductase; Biosyntheses

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.

蛋白质的结构决定了它们的功能。本项目将尝试对酶的几个结构特征进行修饰，以获得更多的生产功能和更高的反应速度。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。私人投资机构将继续从代表不足的少数族裔中招募本科生和研究生参与这一项目。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材，从HS级别开始，扩展到中学级别。这将为这些学生提供设计和创造不同蛋白质的实践经验。拟议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的底物专一性，以便有效地将短链羧酸代谢物还原为醛。这些化合物是常见的、用途广泛的生物合成中间体，很容易进一步转化为烷烃、烯烃、醇或胺。这项建议专门针对CAR突变体，这些突变体能够还原三种丰富的羧酸代谢物，包括D-和L-乳酸(C3底物)以及乙醇酸(两碳底物)。醛产品的进一步减少导致R-或S-1，2-丙二醇和乙二醇的形成，这些都是大量的工业化学品，应用广泛，特别是在聚酯的生产中。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智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Characterization of Carboxylic Acid Reductases for Biocatalytic Synthesis of Industrial Chemicals

• DOI: 10.1002/cbic.201800157
• 发表时间: 2018-07-04
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: Kramer, Levi;Hankore, Erome Daniel;Niu, Wei
• 通讯作者: Niu, Wei

An empirical investigation of organic software product lines

• DOI: 10.1007/s10664-021-09940-0
• 发表时间: 2021-03
• 期刊: Empirical Software Engineering
• 影响因子: 4.1
• 作者: Mikaela Cashman;Justin W. Firestone;Myra B. Cohen;Thammasak Thianniwet;W. Niu

Engineering Carboxylic Acid Reductase (CAR) through a Whole-Cell Growth-Coupled NADPH Recycling Strategy

• DOI: 10.1021/acssynbio.0c00290
• 发表时间: 2020-07-17
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Kramer, Levi;Le, Xuan;Niu, Wei
• 通讯作者: Niu, Wei

Engineering and characterization of hybrid carboxylic acid reductases

• DOI: 10.1016/j.jbiotec.2019.08.008
• 发表时间: 2019-10-10
• 期刊: JOURNAL OF BIOTECHNOLOGY
• 影响因子: 4.1
• 作者: Kramer, Levi;Le, Xuan;Niu, Wei
• 通讯作者: Niu, Wei