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Nat Commun. 2016 Dec 20;7:13806. doi: 10.1038/ncomms13806.

A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains.

Author information

1
Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Abstract

Kinetic models of metabolism at a genome scale that faithfully recapitulate the effect of multiple genetic interventions would be transformative in our ability to reliably design novel overproducing microbial strains. Here, we introduce k-ecoli457, a genome-scale kinetic model of Escherichia coli metabolism that satisfies fluxomic data for wild-type and 25 mutant strains under different substrates and growth conditions. The k-ecoli457 model contains 457 model reactions, 337 metabolites and 295 substrate-level regulatory interactions. Parameterization is carried out using a genetic algorithm by simultaneously imposing all available fluxomic data (about 30 measured fluxes per mutant). The Pearson correlation coefficient between experimental data and predicted product yields for 320 engineered strains spanning 24 product metabolites is 0.84. This is substantially higher than that using flux balance analysis, minimization of metabolic adjustment or maximization of product yield exhibiting systematic errors with correlation coefficients of, respectively, 0.18, 0.37 and 0.47 (k-ecoli457 is available for download at http://www.maranasgroup.com).

PMID:
27996047
PMCID:
PMC5187423
DOI:
10.1038/ncomms13806
[Indexed for MEDLINE]
Free PMC Article

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