RRC ID 35428
Author Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick JD, Osterhout RE, Stephen R, Estadilla J, Teisan S, Schreyer HB, Andrae S, Yang TH, Lee SY, Burk MJ, Van Dien S.
Title Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol.
Journal Nat. Chem. Biol.
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.
Volume 7(7)
Pages 445-52
Published 2011-5-22
DOI 10.1038/nchembio.580
PII nchembio.580
PMID 21602812
MeSH Anaerobiosis Biosynthetic Pathways Butylene Glycols / chemistry Butylene Glycols / metabolism* Escherichia coli / enzymology Escherichia coli / genetics Escherichia coli / metabolism* Fermentation Genetic Engineering Glucose / metabolism Organisms, Genetically Modified / metabolism*
IF 13.843
Times Cited 349
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Prokaryotes E. coli NA