Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol

被引：13

作者：

Yim, Harry ^{[1
]}

Haselbeck, Robert ^{[1
]}

Niu, Wei ^{[1
]}

Pujol-Baxley, Catherine ^{[1
]}

Burgard, Anthony ^{[1
]}

Boldt, Jeff ^{[1
]}

Khandurina, Julia ^{[1
]}

Trawick, John D. ^{[1
]}

Osterhout, Robin E. ^{[1
]}

Stephen, Rosary ^{[1
]}

Estadilla, Jazell ^{[1
]}

Teisan, Sy ^{[1
]}

Schreyer, H. Brett ^{[1
]}

Andrae, Stefan ^{[1
]}

Yang, Tae Hoon ^{[1
]}

Lee, Sang Yup ^{[2
]}

Burk, Mark J. ^{[1
]}

Van Dien, Stephen ^{[1
]}

机构：

[1] Genomat Inc, San Diego, CA USA

[2] Korea Adv Inst Sci & Technol, Inst BioCentury, Ctr Syst & Synthet Biotechnol, Dept Chem & Biomol Engn,Program BK21, Taejon 305701, South Korea

来源：

NATURE CHEMICAL BIOLOGY | 2011年 / 7卷 / 07期

关键词：

PYRUVATE-DEHYDROGENASE; SUCCINIC ACID; CITRATE SYNTHASE; PATHWAY; GENE; K-12; NADH; 4-HYDROXYBUTYRATE; BIOSYNTHESIS; FERMENTATION;

D O I：

10.1038/NCHEMBIO.580

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 gl-1 of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.

引用

页码：445 / 452

页数：8

共 45 条

[41] Probing the roles of key residues in the unique regulatory NADH binding site of type II citrate synthase of Escherichia coli [J].