1. Computational and Systems Biology
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Control and regulation of acetate overflow in Escherichia coli

  1. Pierre Millard  Is a corresponding author
  2. Brice Enjalbert
  3. Sandrine Uttenweiler-Joseph
  4. Jean-Charles Portais
  5. Fabien Letisse
  1. TBI, Universite de Toulouse, CNRS, INRAE, INSA, France
  2. Université de Toulouse, France
Research Article
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Cite this article as: eLife 2021;10:e63661 doi: 10.7554/eLife.63661

Abstract

Overflow metabolism refers to the production of seemingly wasteful by-products by cells during growth on glucose even when oxygen is abundant. Two theories have been proposed to explain acetate overflow in Escherichia coli – global control of the central metabolism and local control of the acetate pathway – but neither accounts for all observations. Here, we develop a kinetic model of E. coli metabolism that quantitatively accounts for observed behaviors and successfully predicts the response of E. coli to new perturbations. We reconcile these theories and clarify the origin, control and regulation of the acetate flux. We also find that, in turns, acetate regulates glucose metabolism by coordinating the expression of glycolytic and TCA genes. Acetate should not be considered a wasteful end-product since it is also a co-substrate and a global regulator of glucose metabolism in E. coli. This has broad implications for our understanding of overflow metabolism.

Data availability

Transcriptomics data have been deposited in ArrayExpress under accession code E-MTAB-9086.The calibrated kinetic model has been deposited in BioModels database under accession code MODEL2005050001.All the scripts used to perform the simulations, to analyse the models and to generate the figures are provided in the supporting files and at https://github.com/MetaSys-LISBP/acetate_regulationAll data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Pierre Millard

    Systems biology, TBI, Universite de Toulouse, CNRS, INRAE, INSA, Toulouse, France
    For correspondence
    millard@insa-toulouse.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8136-9963
  2. Brice Enjalbert

    Systems biology, TBI, Universite de Toulouse, CNRS, INRAE, INSA, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandrine Uttenweiler-Joseph

    Systems biology, TBI, Universite de Toulouse, CNRS, INRAE, INSA, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-Charles Portais

    LISBP, Université de Toulouse, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Fabien Letisse

    Systems biology, TBI, Universite de Toulouse, CNRS, INRAE, INSA, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.

Funding

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (MICA-JC)

  • Pierre Millard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Michael Doebeli, University of British Columbia, Canada

Publication history

  1. Received: October 1, 2020
  2. Accepted: March 12, 2021
  3. Accepted Manuscript published: March 15, 2021 (version 1)
  4. Version of Record published: April 4, 2021 (version 2)

Copyright

© 2021, Millard et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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