Document Detail

Modular optimization of multi-gene pathways for fatty acids production in E. coli.
MedLine Citation:
PMID:  23361000     Owner:  NLM     Status:  In-Data-Review    
Microbial fatty acid-derived fuels have emerged as promising alternatives to petroleum-based transportation fuels. Here we report a modular engineering approach that systematically removed metabolic pathway bottlenecks and led to significant titre improvements in a multi-gene fatty acid metabolic pathway. On the basis of central pathway architecture, E. coli fatty acid biosynthesis was re-cast into three modules: the upstream acetyl coenzyme A formation module; the intermediary acetyl-CoA activation module; and the downstream fatty acid synthase module. Combinatorial optimization of transcriptional levels of these three modules led to the identification of conditions that balance the supply of acetyl-CoA and consumption of malonyl-CoA/ACP. Refining protein translation efficiency by customizing ribosome binding sites for both the upstream acetyl coenzyme A formation and fatty acid synthase modules enabled further production improvement. Fed-batch cultivation of the engineered strain resulted in a final fatty acid production of 8.6 g l(-1). The modular engineering strategies demonstrate a generalized approach to engineering cell factories for valuable metabolites production.
Peng Xu; Qin Gu; Wenya Wang; Lynn Wong; Adam G W Bower; Cynthia H Collins; Mattheos A G Koffas
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  4     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1409     Citation Subset:  IM    
1] Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, USA [2] Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
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