Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis
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Date
2013-01
Publication Type
Journal Article
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yes
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Abstract
One of the key ways in which microbes are thought to regulate their metabolism is by modulating the availability of enzymes through transcriptional regulation. However, the limited success of efforts to manipulate metabolic fluxes by rewiring the transcriptional network has cast doubt on the idea that transcript abundance controls metabolic fluxes. In this study, we investigate control of metabolic flux in the model bacterium Bacillus subtilis by quantifying fluxes, transcripts, and metabolites in eight metabolic states enforced by different environmental conditions. We find that most enzymes whose flux switches between on and off states, such as those involved in substrate uptake, exhibit large corresponding transcriptional changes. However, for the majority of enzymes in central metabolism, enzyme concentrations were insufficient to explain the observed fluxes—only for a number of reactions in the tricarboxylic acid cycle were enzyme changes approximately proportional to flux changes. Surprisingly, substrate changes revealed by metabolomics were also insufficient to explain observed fluxes, leaving a large role for allosteric regulation and enzyme modification in the control of metabolic fluxes.
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published
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Journal / series
Volume
9 (1)
Pages / Article No.
709
Publisher
Nature
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Subject
Central carbon metabolism; Metabolic flux; Transcriptional regulation
Organisational unit
03699 - Stelling, Jörg / Stelling, Jörg
03713 - Sauer, Uwe / Sauer, Uwe