Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis
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 th...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2013-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2013.66 |
| _version_ | 1797225976991580160 |
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| author | Victor Chubukov Markus Uhr Ludovic Le Chat Roelco J Kleijn Matthieu Jules Hannes Link Stephane Aymerich Jörg Stelling Uwe Sauer |
| author_facet | Victor Chubukov Markus Uhr Ludovic Le Chat Roelco J Kleijn Matthieu Jules Hannes Link Stephane Aymerich Jörg Stelling Uwe Sauer |
| author_sort | Victor Chubukov |
| collection | DOAJ |
| description | 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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| id | doaj.art-c50f2e99c3d44e0ea17aeb1ecf3bc065 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-04-24T14:17:35Z |
| publishDate | 2013-01-01 |
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| series | Molecular Systems Biology |
| spelling | doaj.art-c50f2e99c3d44e0ea17aeb1ecf3bc0652024-04-03T08:20:34ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2013.66Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilisVictor Chubukov0Markus Uhr1Ludovic Le Chat2Roelco J Kleijn3Matthieu Jules4Hannes Link5Stephane Aymerich6Jörg Stelling7Uwe Sauer8Institute of Molecular System Biology, ETH Zurich Zurich SwitzerlandDepartment of Biosystems Science and Engineering, SIB Swiss Institute of Bioinformatics, ETH Zurich Zurich SwitzerlandMicalis Institute, INRA, AgroParisTech Thiverval‐Grignon FranceInstitute of Molecular System Biology, ETH Zurich Zurich SwitzerlandMicalis Institute, INRA, AgroParisTech Thiverval‐Grignon FranceInstitute of Molecular System Biology, ETH Zurich Zurich SwitzerlandMicalis Institute, INRA, AgroParisTech Thiverval‐Grignon FranceDepartment of Biosystems Science and Engineering, SIB Swiss Institute of Bioinformatics, ETH Zurich Zurich SwitzerlandInstitute of Molecular System Biology, ETH Zurich Zurich SwitzerlandOne 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.https://doi.org/10.1038/msb.2013.66central carbon metabolismmetabolic fluxtranscriptional regulation |
| spellingShingle | Victor Chubukov Markus Uhr Ludovic Le Chat Roelco J Kleijn Matthieu Jules Hannes Link Stephane Aymerich Jörg Stelling Uwe Sauer Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis Molecular Systems Biology central carbon metabolism metabolic flux transcriptional regulation |
| title | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_full | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_fullStr | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_full_unstemmed | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_short | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_sort | transcriptional regulation is insufficient to explain substrate induced flux changes in bacillus subtilis |
| topic | central carbon metabolism metabolic flux transcriptional regulation |
| url | https://doi.org/10.1038/msb.2013.66 |
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