In silico identification of switching nodes in metabolic networks
Cells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (for In Silico Ide...
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2024-10-01
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| author | Mairet, Francis |
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| description | Cells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (for In Silico Identification of Switches) is proposed to locate these nodes in a metabolic network, based on the analysis of a set of flux vectors (obtained e.g. by parsimonious flux balance analysis with different inputs). A metabolite is considered as a switch if the fluxes at this point are redirected in a different way when conditions change. The soundness of ISIS is shown with four case studies, using both core and genome-scale metabolic networks of Escherichia coli, Saccharomyces cerevisiae and the diatom Phaeodactylum tricornutum. Through these examples, we show that ISIS can identify hot-spots where fluxes are reoriented. Additionally, switch metabolites are deeply involved in post-translational modification of proteins, showing their importance in cellular regulation. In P. tricornutum, we show that Erythrose 4-phosphate is an important switch metabolite for mixotrophy suggesting the importance of this metabolite in the non-oxidative pentose phosphate pathway to orchestrate the flux variations between glycolysis, the Calvin cycle and the oxidative pentose phosphate pathway when the trophic mode changes. Finally, a comparison between ISIS and reporter metabolites identified with transcriptomic data confirms the key role of metabolites such as L-glutamate or L-aspartate in the yeast response to nitrogen input variation. Overall, ISIS opens up new possibilities for studying cellular metabolism and regulation, as well as potentially for developing metabolic engineering. |
| format | Article |
| id | doaj-art-e85417b6af3b43a9ad5412f7dd4de395 |
| institution | Kabale University |
| issn | 2804-3871 |
| language | English |
| publishDate | 2024-10-01 |
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| spelling | doaj-art-e85417b6af3b43a9ad5412f7dd4de3952025-02-07T10:17:17ZengPeer Community InPeer Community Journal2804-38712024-10-01410.24072/pcjournal.48010.24072/pcjournal.480In silico identification of switching nodes in metabolic networks Mairet, Francis0https://orcid.org/0000-0002-3236-9772Ifremer, PHYTOX, Laboratoire PHYSALG, F-44000 Nantes, FranceCells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (for In Silico Identification of Switches) is proposed to locate these nodes in a metabolic network, based on the analysis of a set of flux vectors (obtained e.g. by parsimonious flux balance analysis with different inputs). A metabolite is considered as a switch if the fluxes at this point are redirected in a different way when conditions change. The soundness of ISIS is shown with four case studies, using both core and genome-scale metabolic networks of Escherichia coli, Saccharomyces cerevisiae and the diatom Phaeodactylum tricornutum. Through these examples, we show that ISIS can identify hot-spots where fluxes are reoriented. Additionally, switch metabolites are deeply involved in post-translational modification of proteins, showing their importance in cellular regulation. In P. tricornutum, we show that Erythrose 4-phosphate is an important switch metabolite for mixotrophy suggesting the importance of this metabolite in the non-oxidative pentose phosphate pathway to orchestrate the flux variations between glycolysis, the Calvin cycle and the oxidative pentose phosphate pathway when the trophic mode changes. Finally, a comparison between ISIS and reporter metabolites identified with transcriptomic data confirms the key role of metabolites such as L-glutamate or L-aspartate in the yeast response to nitrogen input variation. Overall, ISIS opens up new possibilities for studying cellular metabolism and regulation, as well as potentially for developing metabolic engineering.https://peercommunityjournal.org/articles/10.24072/pcjournal.480/Genome-scale metabolic model, Branching point, Reporter metabolites, Flux Balance Analysis |
| spellingShingle | Mairet, Francis In silico identification of switching nodes in metabolic networks Peer Community Journal Genome-scale metabolic model, Branching point, Reporter metabolites, Flux Balance Analysis |
| title | In silico identification of switching nodes in metabolic networks
|
| title_full | In silico identification of switching nodes in metabolic networks
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| title_fullStr | In silico identification of switching nodes in metabolic networks
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| title_full_unstemmed | In silico identification of switching nodes in metabolic networks
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| title_short | In silico identification of switching nodes in metabolic networks
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| title_sort | in silico identification of switching nodes in metabolic networks |
| topic | Genome-scale metabolic model, Branching point, Reporter metabolites, Flux Balance Analysis |
| url | https://peercommunityjournal.org/articles/10.24072/pcjournal.480/ |
| work_keys_str_mv | AT mairetfrancis insilicoidentificationofswitchingnodesinmetabolicnetworks |