title: Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol.
abstract: 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(-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.
authors: Genomatica, Inc., San Diego, California, USA.
authors: Harry
authors: H
authors: Yim
authors: Robert
authors: R
authors: Haselbeck
authors: Wei
authors: W
authors: Niu
authors: Catherine
authors: C
authors: Pujol-Baxley
authors: Anthony
authors: A
authors: Burgard
authors: Jeff
authors: J
authors: Boldt
authors: Julia
authors: J
authors: Khandurina
authors: John D
authors: JD
authors: Trawick
authors: Robin E
authors: RE
authors: Osterhout
authors: Rosary
authors: R
authors: Stephen
authors: Jazell
authors: J
authors: Estadilla
authors: Sy
authors: S
authors: Teisan
authors: H Brett
authors: HB
authors: Schreyer
authors: Stefan
authors: S
authors: Andrae
authors: Tae Hoon
authors: TH
authors: Yang
authors: Sang Yup
authors: SY
authors: Lee
authors: Mark J
authors: MJ
authors: Burk
authors: Stephen
authors: S
authors: Van Dien
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