Maintaining maximal metabolic flux by gene expression control

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

One of the marvels of biology is the phenotypic plasticity of microorganisms. It allows them to maintain high growth rates across conditions. Studies suggest that cells can express metabolic enzymes at tuned concentrations through adjustment of gene expression. The associated transcription factors are often regulated by intracellular metabolites. Here we study metabolite-mediated regulation of metabolic-gene expression that maximises metabolic fluxes across conditions. We developed an adaptive control theory, qORAC (for ‘Specific Flux (q) Optimization by Robust Adaptive Control’), and illustrate it with several examples of metabolic pathways. The key feature of the theory is that it does not require knowledge of the regulatory network, only of the metabolic part. We derive that maximal metabolic flux can be maintained in the face of varying N environmental parameters only if the number of transcription-factor binding metabolites is at least equal to N. The controlling circuits appear to require simple biochemical kinetics. We conclude that microorganisms likely can achieve maximal rates in metabolic pathways, in the face of environmental changes.

Original languageEnglish
Article numbere1006412
Pages (from-to)1-20
Number of pages20
JournalPLoS Computational Biology
Volume14
Issue number9
DOIs
Publication statusPublished - 20 Sep 2018

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Metabolites
Metabolic Networks and Pathways
Gene expression
Gene Expression
gene expression
metabolite
Transcription factors
Microorganisms
Transcription Factor
Fluxes
metabolites
biochemical pathways
Pathway
Transcription Factors
transcription factors
microorganism
Robust Adaptive Control
microorganisms
Regulatory Networks
Gene Expression Regulation

Cite this

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abstract = "One of the marvels of biology is the phenotypic plasticity of microorganisms. It allows them to maintain high growth rates across conditions. Studies suggest that cells can express metabolic enzymes at tuned concentrations through adjustment of gene expression. The associated transcription factors are often regulated by intracellular metabolites. Here we study metabolite-mediated regulation of metabolic-gene expression that maximises metabolic fluxes across conditions. We developed an adaptive control theory, qORAC (for ‘Specific Flux (q) Optimization by Robust Adaptive Control’), and illustrate it with several examples of metabolic pathways. The key feature of the theory is that it does not require knowledge of the regulatory network, only of the metabolic part. We derive that maximal metabolic flux can be maintained in the face of varying N environmental parameters only if the number of transcription-factor binding metabolites is at least equal to N. The controlling circuits appear to require simple biochemical kinetics. We conclude that microorganisms likely can achieve maximal rates in metabolic pathways, in the face of environmental changes.",
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Maintaining maximal metabolic flux by gene expression control. / Planqué, Robert; Hulshof, Josephus; Teusink, Bas; Hendriks, Johannes C.; Bruggeman, Frank J.

In: PLoS Computational Biology, Vol. 14, No. 9, e1006412, 20.09.2018, p. 1-20.

Research output: Contribution to JournalArticleAcademicpeer-review

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