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Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli

Millard, Pierre ; Smallbone, Kieran ; Mendes, Pedro Maranas, Costas D.

PLoS computational biology, 2017-02, Vol.13 (2), p.e1005396-e1005396 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli
Autor: Millard, Pierre ; Smallbone, Kieran ; Mendes, Pedro
Maranas, Costas D.
Assuntos: Bioenergetics ; Biology and Life Sciences ; Biotechnology ; Carbon ; Cell Proliferation - physiology ; Chemical and Process Engineering ; Colleges & universities ; Computer and Information Sciences ; Computer science ; Computer Simulation ; Datasets ; E coli ; Energy metabolism ; Energy Metabolism - physiology ; Engineering Sciences ; Enzymes ; Escherichia coli ; Escherichia coli - cytology ; Escherichia coli - metabolism ; Funding ; Gene expression ; Gene Expression Regulation, Bacterial - physiology ; Gene Expression Regulation, Enzymologic - physiology ; Glucose - metabolism ; Life Sciences ; Metabolic Flux Analysis - methods ; Metabolic Networks and Pathways - physiology ; Metabolism ; Metabolites ; Microbiology and Parasitology ; Models, Biological ; Observations ; Physical Sciences ; Physiological aspects ; Signal Transduction - physiology ; Synthetic biology
É parte de: PLoS computational biology, 2017-02, Vol.13 (2), p.e1005396-e1005396
Notas: new_version
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Conceptualization: PMi PMe KS.Data curation: PMi.Formal analysis: PMi PMe KS.Funding acquisition: PMi PMe KS.Investigation: PMi.Methodology: PMi KS PMe.Project administration: PMi PMe.Resources: PMi PMe KS.Software: PMi.Supervision: PMe.Validation: PMi.Visualization: PMi.Writing – original draft: PMi.Writing – review & editing: PMi PMe KS.
The authors have declared that no competing interests exist.
Descrição: The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control") and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool) to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth), while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.
Editor: United States: Public Library of Science
Idioma: Inglês

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Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli

Millard, Pierre ; Smallbone, Kieran ; Mendes, Pedro Maranas, Costas D.

United States: Public Library of Science

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