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

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  • Ali Khodayari

    (The Pennsylvania State University, University Park)

  • Costas D. Maranas

    (The Pennsylvania State University, University Park)

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 ).

Suggested Citation

  • Ali Khodayari & Costas D. Maranas, 2016. "A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13806
    DOI: 10.1038/ncomms13806
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    Cited by:

    1. Lukas Bromig & Andreas Kremling & Alberto Marin-Sanguino, 2020. "Understanding biochemical design principles with ensembles of canonical non-linear models," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-27, April.
    2. Gaoyang Li & Li Liu & Wei Du & Huansheng Cao, 2023. "Local flux coordination and global gene expression regulation in metabolic modeling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Ljubisa Miskovic & Jonas Béal & Michael Moret & Vassily Hatzimanikatis, 2019. "Uncertainty reduction in biochemical kinetic models: Enforcing desired model properties," PLOS Computational Biology, Public Library of Science, vol. 15(8), pages 1-29, August.

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