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.

蛋白质的结构决定其功能。该项目将尝试修改酶的几个结构特征，以获得更有效的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量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经验。 PI将继续招募来自代表性不足的少数民族的本科生和研究生，从事该项目。 PI还将通过内布拉斯加州EPSCOR青年科学家计划组装和分发教育套件，从HS级别开始，并扩展到中学水平。这将为这些学生提供设计和创建不同蛋白质的动手经验。拟议的工作着重于羧酸还原酶（CAR）的研究和工程。该项目的目的是扩大汽车的底物特异性，以便将短链羧酸代谢物有效地减少到醛中。它们是常见和多功能的生物合成中间体，很容易被进一步转化为烷烃，烷烃，醇或胺。该建议专门针对的是在还原三种丰富的羧酸代谢产物（包括D-和L-乳酸酸（C3底物））和乙醇酸（两碳基质）的汽车突变体。醛产物的进一步降低导致R-或S-1,2-丙二醇和乙二醇的形成，它们是具有广泛应用的批量工业化学物质，尤其是在Polyesters的生产中。该奖项反映了NSF的立法任务，并被认为是通过基金会的智力效果和广泛的评估来评估的，并值得通过评估来进行评估。

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