BioChem - DOS

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

Nature chemical biology

Yim, Harry; Haselbeck, Robert; Niu, Wei; Pujol-Baxley, Catherine; Burgard, Anthony; Boldt, Jeff; Khandurina, Julia; Trawick, John D; Osterhout, Robin E; Stephen, Rosary; Estadilla, Jazell; Teisan, Sy; Schreyer, H Brett; Andrae, Stefan; Yang, Tae Hoon; Lee, Sang Yup; Burk, Mark J; Van Dien, Stephen

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 g l<SUP>？?1</SUP> 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.

2011

Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

1552-4450

1552-4469

7

7

pp.445-452

10.1038/nchembio.580

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