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

Khodayari, Ali; Maranas, Costas D.

doi:10.1038/ncomms13806

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

Journal Article · Tue Dec 20 00:00:00 EST 2016 · Nature Communications

DOI:https://doi.org/10.1038/ncomms13806· OSTI ID:1360140

Khodayari, Ali ^[1]; Maranas, Costas D. ^[1]

The Pennsylvania State Univ., University Park, PA (United States)

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). Furthermore, 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.

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Research Organization:: Pennsylvania State Univ., University Park, PA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0012377

OSTI ID:: 1360140

Journal Information:: Nature Communications, Vol. 7; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 126 works

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