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Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli
Many microbes exhibit nutrient preferences, exemplified by the “hierarchical” consumption of certain carbon substrates. Here we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarch...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925339/ https://www.ncbi.nlm.nih.gov/pubmed/31819215 http://dx.doi.org/10.1038/s41564-019-0610-7 |
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author | Okano, Hiroyuki Hermsen, Rutger Kochanowski, Karl Hwa, Terence |
author_facet | Okano, Hiroyuki Hermsen, Rutger Kochanowski, Karl Hwa, Terence |
author_sort | Okano, Hiroyuki |
collection | PubMed |
description | Many microbes exhibit nutrient preferences, exemplified by the “hierarchical” consumption of certain carbon substrates. Here we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates. A detailed study of glycerol uptake finds that it is fully suppressed if the uptake flux of another glycolytic substrate exceeds a threshold, set to the influx obtained when grown on glycerol alone. Below this threshold, limited glycerol uptake is “supplemented” such that the total carbon uptake is maintained at the threshold. This behavior results from total-flux feedback mediated by cAMP-Crp signaling, but also requires inhibition by regulator fructose-1,6-bisphosphate, which senses the upper glycolytic flux and ensures that glycerol uptake defers to other glycolytic substrates but not to gluconeogenic ones. A quantitative model reproduces all observed utilization patterns including those of key mutants. The proposed mechanism relies on differential regulation of uptake enzymes and requires a specific operon organization. This organization is found conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microbes. |
format | Online Article Text |
id | pubmed-6925339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-69253392020-06-09 Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli Okano, Hiroyuki Hermsen, Rutger Kochanowski, Karl Hwa, Terence Nat Microbiol Article Many microbes exhibit nutrient preferences, exemplified by the “hierarchical” consumption of certain carbon substrates. Here we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates. A detailed study of glycerol uptake finds that it is fully suppressed if the uptake flux of another glycolytic substrate exceeds a threshold, set to the influx obtained when grown on glycerol alone. Below this threshold, limited glycerol uptake is “supplemented” such that the total carbon uptake is maintained at the threshold. This behavior results from total-flux feedback mediated by cAMP-Crp signaling, but also requires inhibition by regulator fructose-1,6-bisphosphate, which senses the upper glycolytic flux and ensures that glycerol uptake defers to other glycolytic substrates but not to gluconeogenic ones. A quantitative model reproduces all observed utilization patterns including those of key mutants. The proposed mechanism relies on differential regulation of uptake enzymes and requires a specific operon organization. This organization is found conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microbes. 2019-12-09 2020-01 /pmc/articles/PMC6925339/ /pubmed/31819215 http://dx.doi.org/10.1038/s41564-019-0610-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Okano, Hiroyuki Hermsen, Rutger Kochanowski, Karl Hwa, Terence Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title | Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title_full | Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title_fullStr | Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title_full_unstemmed | Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title_short | Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli |
title_sort | regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925339/ https://www.ncbi.nlm.nih.gov/pubmed/31819215 http://dx.doi.org/10.1038/s41564-019-0610-7 |
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