Document Detail


An Integrated Computational and Experimental Study for Overproducing Fatty Acids in Escherichia coli.
MedLine Citation:
PMID:  23036703     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increasing demands for petroleum have stimulated sustainable ways to produce chemicals and biofuels. Specifically, fatty acids of varying chain lengths (C(6)-C(16)) naturally synthesized in many organisms are promising starting points for the catalytic production of industrial chemicals and diesel-like biofuels. However, bio-production of fatty acids from plants and other microbial production hosts relies heavily on manipulating tightly regulated fatty acid biosynthetic pathways. In addition, precursors for fatty acids are used along other central metabolic pathways for the production of amino acids and biomass, which further complicates the engineering of microbial hosts for higher yields. Here, we demonstrate an iterative metabolic engineering effort that integrates computationally driven predictions and metabolic flux analysis techniques to meet this challenge. The OptForce procedure was used for suggesting and prioritizing genetic manipulations that overproduce fatty acids of different chain lengths from C(6) to C(16) starting with wild-type E. coli. We identified some common but mostly chain-specific genetic interventions alluding to the possibility of fine-tuning overproduction for specific fatty acid chain lengths. In accordance with the OptForce prioritization of interventions, fabZ and acyl-ACP thioesterase were upregulated and fadD was deleted to arrive at a strain that produces 1.70g/L and 0.14g fatty acid/g glucose (∼39% maximum theoretical yield) of C(14-16) fatty acid in minimal M9 medium. These results highlight the benefit of using computational strain design and flux analysis tools in the design of recombinant strains of E. coli to produce free fatty acids.
Authors:
Sridhar Ranganathan; Ting Wei Tee; Anupam Chowdhury; Ali R Zomorrodi; Jong Moon Yoon; Yanfen Fu; Jacqueline V Shanks; Costas D Maranas
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  Metabolic engineering     Volume:  -     ISSN:  1096-7184     ISO Abbreviation:  Metab. Eng.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815657     Medline TA:  Metab Eng     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA.
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