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Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis
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| Zeitschriftentitel: | Molecular Systems Biology |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | Molecular Systems Biology, 9, 2013, 1 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Springer Science and Business Media LLC
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| Schlagwörter: |
| author_facet |
Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe |
|---|---|
| author |
Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe |
| spellingShingle |
Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe Molecular Systems Biology Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis Applied Mathematics Computational Theory and Mathematics General Agricultural and Biological Sciences General Immunology and Microbiology General Biochemistry, Genetics and Molecular Biology Information Systems |
| author_sort |
chubukov, victor |
| spelling |
Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe 1744-4292 1744-4292 Springer Science and Business Media LLC Applied Mathematics Computational Theory and Mathematics General Agricultural and Biological Sciences General Immunology and Microbiology General Biochemistry, Genetics and Molecular Biology Information Systems http://dx.doi.org/10.1038/msb.2013.66 <jats:p>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 <jats:italic>Bacillus subtilis</jats:italic> 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.</jats:p> Transcriptional regulation is insufficient to explain substrate‐induced flux changes in <i>Bacillus subtilis</i> Molecular Systems Biology |
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10.1038/msb.2013.66 |
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Molecular Systems Biology |
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| title |
Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| title_unstemmed |
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 <i>bacillus subtilis</i> |
| topic |
Applied Mathematics Computational Theory and Mathematics General Agricultural and Biological Sciences General Immunology and Microbiology General Biochemistry, Genetics and Molecular Biology Information Systems |
| url |
http://dx.doi.org/10.1038/msb.2013.66 |
| publishDate |
2013 |
| physical |
|
| description |
<jats:p>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 <jats:italic>Bacillus subtilis</jats:italic> 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.</jats:p> |
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| author | Chubukov, Victor, Uhr, Markus, Le Chat, Ludovic, Kleijn, Roelco J, Jules, Matthieu, Link, Hannes, Aymerich, Stephane, Stelling, Jörg, Sauer, Uwe |
| author_facet | Chubukov, Victor, Uhr, Markus, Le Chat, Ludovic, Kleijn, Roelco J, Jules, Matthieu, Link, Hannes, Aymerich, Stephane, Stelling, Jörg, Sauer, Uwe, Chubukov, Victor, Uhr, Markus, Le Chat, Ludovic, Kleijn, Roelco J, Jules, Matthieu, Link, Hannes, Aymerich, Stephane, Stelling, Jörg, Sauer, Uwe |
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| description | <jats:p>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 <jats:italic>Bacillus subtilis</jats:italic> 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.</jats:p> |
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| spelling | Chubukov, Victor Uhr, Markus Le Chat, Ludovic Kleijn, Roelco J Jules, Matthieu Link, Hannes Aymerich, Stephane Stelling, Jörg Sauer, Uwe 1744-4292 1744-4292 Springer Science and Business Media LLC Applied Mathematics Computational Theory and Mathematics General Agricultural and Biological Sciences General Immunology and Microbiology General Biochemistry, Genetics and Molecular Biology Information Systems http://dx.doi.org/10.1038/msb.2013.66 <jats:p>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 <jats:italic>Bacillus subtilis</jats:italic> 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.</jats:p> Transcriptional regulation is insufficient to explain substrate‐induced flux changes in <i>Bacillus subtilis</i> Molecular Systems Biology |
| spellingShingle | Chubukov, Victor, Uhr, Markus, Le Chat, Ludovic, Kleijn, Roelco J, Jules, Matthieu, Link, Hannes, Aymerich, Stephane, Stelling, Jörg, Sauer, Uwe, Molecular Systems Biology, Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis, Applied Mathematics, Computational Theory and Mathematics, General Agricultural and Biological Sciences, General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Information Systems |
| 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 <i>bacillus subtilis</i> |
| title_unstemmed | Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis |
| topic | Applied Mathematics, Computational Theory and Mathematics, General Agricultural and Biological Sciences, General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Information Systems |
| url | http://dx.doi.org/10.1038/msb.2013.66 |