Maintaining maximal metabolic flux by gene expression control.

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 a...

Full description

Bibliographic Details
Main Authors: Robert Planqué, Josephus Hulshof, Bas Teusink, Johannes C Hendriks, Frank J Bruggeman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-09-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC6168163?pdf=render
_version_ 1811268297476276224
author Robert Planqué
Josephus Hulshof
Bas Teusink
Johannes C Hendriks
Frank J Bruggeman
author_facet Robert Planqué
Josephus Hulshof
Bas Teusink
Johannes C Hendriks
Frank J Bruggeman
author_sort Robert Planqué
collection DOAJ
description 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.
first_indexed 2024-04-12T21:20:24Z
format Article
id doaj.art-66255b5bc4de4b739fcdf705c66c8044
institution Directory Open Access Journal
issn 1553-734X
1553-7358
language English
last_indexed 2024-04-12T21:20:24Z
publishDate 2018-09-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Computational Biology
spelling doaj.art-66255b5bc4de4b739fcdf705c66c80442022-12-22T03:16:20ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582018-09-01149e100641210.1371/journal.pcbi.1006412Maintaining maximal metabolic flux by gene expression control.Robert PlanquéJosephus HulshofBas TeusinkJohannes C HendriksFrank J BruggemanOne 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.http://europepmc.org/articles/PMC6168163?pdf=render
spellingShingle Robert Planqué
Josephus Hulshof
Bas Teusink
Johannes C Hendriks
Frank J Bruggeman
Maintaining maximal metabolic flux by gene expression control.
PLoS Computational Biology
title Maintaining maximal metabolic flux by gene expression control.
title_full Maintaining maximal metabolic flux by gene expression control.
title_fullStr Maintaining maximal metabolic flux by gene expression control.
title_full_unstemmed Maintaining maximal metabolic flux by gene expression control.
title_short Maintaining maximal metabolic flux by gene expression control.
title_sort maintaining maximal metabolic flux by gene expression control
url http://europepmc.org/articles/PMC6168163?pdf=render
work_keys_str_mv AT robertplanque maintainingmaximalmetabolicfluxbygeneexpressioncontrol
AT josephushulshof maintainingmaximalmetabolicfluxbygeneexpressioncontrol
AT basteusink maintainingmaximalmetabolicfluxbygeneexpressioncontrol
AT johanneschendriks maintainingmaximalmetabolicfluxbygeneexpressioncontrol
AT frankjbruggeman maintainingmaximalmetabolicfluxbygeneexpressioncontrol