Global coordination of metabolic pathways in Escherichia coli by active and passive regulation
Abstract Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanis...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-04-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202010064 |
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| author | Karl Kochanowski Hiroyuki Okano Vadim Patsalo James Williamson Uwe Sauer Terence Hwa |
| author_facet | Karl Kochanowski Hiroyuki Okano Vadim Patsalo James Williamson Uwe Sauer Terence Hwa |
| author_sort | Karl Kochanowski |
| collection | DOAJ |
| description | Abstract Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli. Integrating protein, metabolite, and flux changes in genetically implemented catabolic or anabolic limitations, we show that combined global and local mechanisms coordinate the response to metabolic limitations. To allocate proteomic resources between catabolism and anabolism, E. coli uses a simple global gene regulatory program. Surprisingly, this program is largely implemented by a single transcription factor, Crp, which directly activates the expression of catabolic enzymes and indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, metabolic fluxes are not controlled by this regulatory program alone; instead, fluxes are adjusted mostly through passive changes in the local metabolite concentrations. These mechanisms constitute a simple but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring robust coordination of individual metabolic reactions. |
| format | Article |
| id | doaj-art-9d87f7ba792142a3a79dabdc70a48189 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-9d87f7ba792142a3a79dabdc70a481892025-08-20T03:46:32ZengSpringer NatureMolecular Systems Biology1744-42922021-04-0117411410.15252/msb.202010064Global coordination of metabolic pathways in Escherichia coli by active and passive regulationKarl Kochanowski0Hiroyuki Okano1Vadim Patsalo2James Williamson3Uwe Sauer4Terence Hwa5Institute of Molecular Systems Biology, ETH ZurichDepartment of Physics, University of California at San DiegoDepartment of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research InstituteInstitute of Molecular Systems Biology, ETH ZurichDepartment of Physics, University of California at San DiegoAbstract Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli. Integrating protein, metabolite, and flux changes in genetically implemented catabolic or anabolic limitations, we show that combined global and local mechanisms coordinate the response to metabolic limitations. To allocate proteomic resources between catabolism and anabolism, E. coli uses a simple global gene regulatory program. Surprisingly, this program is largely implemented by a single transcription factor, Crp, which directly activates the expression of catabolic enzymes and indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, metabolic fluxes are not controlled by this regulatory program alone; instead, fluxes are adjusted mostly through passive changes in the local metabolite concentrations. These mechanisms constitute a simple but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring robust coordination of individual metabolic reactions.https://doi.org/10.15252/msb.20201006413C flux analysisCrpmetabolomicsproteomicsregulation analysis |
| spellingShingle | Karl Kochanowski Hiroyuki Okano Vadim Patsalo James Williamson Uwe Sauer Terence Hwa Global coordination of metabolic pathways in Escherichia coli by active and passive regulation Molecular Systems Biology 13C flux analysis Crp metabolomics proteomics regulation analysis |
| title | Global coordination of metabolic pathways in Escherichia coli by active and passive regulation |
| title_full | Global coordination of metabolic pathways in Escherichia coli by active and passive regulation |
| title_fullStr | Global coordination of metabolic pathways in Escherichia coli by active and passive regulation |
| title_full_unstemmed | Global coordination of metabolic pathways in Escherichia coli by active and passive regulation |
| title_short | Global coordination of metabolic pathways in Escherichia coli by active and passive regulation |
| title_sort | global coordination of metabolic pathways in escherichia coli by active and passive regulation |
| topic | 13C flux analysis Crp metabolomics proteomics regulation analysis |
| url | https://doi.org/10.15252/msb.202010064 |
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