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Engineering E. coli for direct production of 1,4-butanediol

Researchers at Genomatica report on their metabolic engineering of E. coli for the direct production of 1,4-butanediol (BDO) (earlier post), an important commodity chemical used in polymers, in a paper in the journal Nature Chemical Biology.

In March, Genomatica and Tate & Lyle signed a joint development agreement for the demonstration-scale production of Genomatica’s Bio-BDO. The Genomatica process produces the same BDO product that is currently made from a variety of petroleum-derived feedstocks, but uses 100% renewable feedstocks instead.

BDO is currently used to manufacture more than 2.5 million tons annually of valuable polymers.

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-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.

—Yim et al.


  • Harry Yim et al. (2011) Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nature Chemical Biology (2011) doi: 10.1038/nchembio.580


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