Control and regulation of acetate overflow in Escherichia coli

Author:

Millard Pierre12ORCID,Enjalbert Brice1ORCID,Uttenweiler-Joseph Sandrine1ORCID,Portais Jean-Charles123ORCID,Létisse Fabien14ORCID

Affiliation:

1. TBI, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France

2. MetaToul-MetaboHUB, National Infrastructure of Metabolomics and Fluxomics, Toulouse, France

3. RESTORE, Université de Toulouse, INSERM U1031, CNRS 5070, Université Toulouse III - Paul Sabatier, EFS, Toulouse, France

4. Université Toulouse III - Paul Sabatier, Toulouse, France

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 behaviours 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.

Funder

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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