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Basic and applied uses of genome‐scale metabolic network reconstructions of Escherichia coli

Douglas McCloskey, Bernhard Ø Palsson, Adam M Feist

Author Affiliations

  1. Douglas McCloskey1,
  2. Bernhard Ø Palsson1,2 and
  3. Adam M Feist*,1,2
  1. 1 Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
  2. 2 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark
  1. *Corresponding author. Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093‐0412, USA. Tel.:+1 858 822 3181; Fax:+1 858 822 3120; E‐mail: afeist{at}ucsd.edu
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Abstract

The genome‐scale model (GEM) of metabolism in the bacterium Escherichia coli K‐12 has been in development for over a decade and is now in wide use. GEM‐enabled studies of E. coli have been primarily focused on six applications: (1) metabolic engineering, (2) model‐driven discovery, (3) prediction of cellular phenotypes, (4) analysis of biological network properties, (5) studies of evolutionary processes, and (6) models of interspecies interactions. In this review, we provide an overview of these applications along with a critical assessment of their successes and limitations, and a perspective on likely future developments in the field. Taken together, the studies performed over the past decade have established a genome‐scale mechanistic understanding of genotype–phenotype relationships in E. coli metabolism that forms the basis for similar efforts for other microbial species. Future challenges include the expansion of GEMs by integrating additional cellular processes beyond metabolism, the identification of key constraints based on emerging data types, and the development of computational methods able to handle such large‐scale network models with sufficient accuracy.

Mol Syst Biol. 9: 661

  • Received August 23, 2012.
  • Accepted March 11, 2013.
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This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

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