Molecular Systems Biology | |
Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis | |
Victor Chubukov3  Markus Uhr1  Ludovic Le Chat2  Roelco J Kleijn3  Matthieu Jules2  Hannes Link3  Stephane Aymerich2  Jörg Stelling1  | |
[1] Department of Biosystems Science and Engineering, SIB Swiss Institute of Bioinformatics, ETH Zurich, Zurich, Switzerland;Micalis Institute, INRA, AgroParisTech, Thiverval-Grignon, France;Institute of Molecular System Biology, ETH Zurich, Zurich, Switzerland | |
关键词: central carbon metabolism; metabolic flux; transcriptional regulation; | |
DOI : 10.1038/msb.2013.66 | |
来源: Wiley | |
【 摘 要 】
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. Regulation of enzyme expression is one key mechanism by which cells control their metabolic programs. In this work, a quantitative analysis of metabolism in a model bacterium under different conditions shows that expression alone cannot explain the majority of the observed metabolic changes.Abstract
Synopsis
【 授权许可】
CC BY-NC-SA
Copyright © 2013 EMBO and Macmillan Publishers Limited
Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
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