Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing
Abstract Central carbon metabolism is highly conserved across microbial species, but can catalyze very different pathways depending on the organism and their ecological niche. Here, we study the dynamic reorganization of central metabolism after switches between the two major opposing pathway config...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-01-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202110704 |
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| _version_ | 1849331533790314496 |
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| author | Severin Josef Schink Dimitris Christodoulou Avik Mukherjee Edward Athaide Viktoria Brunner Tobias Fuhrer Gary Andrew Bradshaw Uwe Sauer Markus Basan |
| author_facet | Severin Josef Schink Dimitris Christodoulou Avik Mukherjee Edward Athaide Viktoria Brunner Tobias Fuhrer Gary Andrew Bradshaw Uwe Sauer Markus Basan |
| author_sort | Severin Josef Schink |
| collection | DOAJ |
| description | Abstract Central carbon metabolism is highly conserved across microbial species, but can catalyze very different pathways depending on the organism and their ecological niche. Here, we study the dynamic reorganization of central metabolism after switches between the two major opposing pathway configurations of central carbon metabolism, glycolysis, and gluconeogenesis in Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas putida. We combined growth dynamics and dynamic changes in intracellular metabolite levels with a coarse‐grained model that integrates fluxes, regulation, protein synthesis, and growth and uncovered fundamental limitations of the regulatory network: After nutrient shifts, metabolite concentrations collapse to their equilibrium, rendering the cell unable to sense which direction the flux is supposed to flow through the metabolic network. The cell can partially alleviate this by picking a preferred direction of regulation at the expense of increasing lag times in the opposite direction. Moreover, decreasing both lag times simultaneously comes at the cost of reduced growth rate or higher futile cycling between metabolic enzymes. These three trade‐offs can explain why microorganisms specialize for either glycolytic or gluconeogenic substrates and can help elucidate the complex growth patterns exhibited by different microbial species. |
| format | Article |
| id | doaj-art-3ca31f39b3384080b5d57cdc605149c9 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-3ca31f39b3384080b5d57cdc605149c92025-08-20T03:46:32ZengSpringer NatureMolecular Systems Biology1744-42922022-01-0118111410.15252/msb.202110704Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensingSeverin Josef Schink0Dimitris Christodoulou1Avik Mukherjee2Edward Athaide3Viktoria Brunner4Tobias Fuhrer5Gary Andrew Bradshaw6Uwe Sauer7Markus Basan8Systems Biology Department, Harvard Medical SchoolSystems Biology Department, Harvard Medical SchoolSystems Biology Department, Harvard Medical SchoolApplied Mathematics Department, Harvard CollegeInstitute of Molecular Systems Biology, ETH ZurichInstitute of Molecular Systems Biology, ETH ZurichLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical SchoolInstitute of Molecular Systems Biology, ETH ZurichSystems Biology Department, Harvard Medical SchoolAbstract Central carbon metabolism is highly conserved across microbial species, but can catalyze very different pathways depending on the organism and their ecological niche. Here, we study the dynamic reorganization of central metabolism after switches between the two major opposing pathway configurations of central carbon metabolism, glycolysis, and gluconeogenesis in Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas putida. We combined growth dynamics and dynamic changes in intracellular metabolite levels with a coarse‐grained model that integrates fluxes, regulation, protein synthesis, and growth and uncovered fundamental limitations of the regulatory network: After nutrient shifts, metabolite concentrations collapse to their equilibrium, rendering the cell unable to sense which direction the flux is supposed to flow through the metabolic network. The cell can partially alleviate this by picking a preferred direction of regulation at the expense of increasing lag times in the opposite direction. Moreover, decreasing both lag times simultaneously comes at the cost of reduced growth rate or higher futile cycling between metabolic enzymes. These three trade‐offs can explain why microorganisms specialize for either glycolytic or gluconeogenic substrates and can help elucidate the complex growth patterns exhibited by different microbial species.https://doi.org/10.15252/msb.202110704flux sensinglag timemetabolismspecializationtrade‐off |
| spellingShingle | Severin Josef Schink Dimitris Christodoulou Avik Mukherjee Edward Athaide Viktoria Brunner Tobias Fuhrer Gary Andrew Bradshaw Uwe Sauer Markus Basan Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing Molecular Systems Biology flux sensing lag time metabolism specialization trade‐off |
| title | Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| title_full | Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| title_fullStr | Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| title_full_unstemmed | Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| title_short | Glycolysis/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| title_sort | glycolysis gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing |
| topic | flux sensing lag time metabolism specialization trade‐off |
| url | https://doi.org/10.15252/msb.202110704 |
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