Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli
- 9 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Microbiology
- Vol. 5 (1), 206-215
- https://doi.org/10.1038/s41564-019-0610-7
Abstract
Many microorganisms 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, which is 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 behaviour results from total-flux feedback mediated by cAMP–Crp signalling but also requires inhibition by the 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 of the observed utilization patterns, including those of key mutants. The proposed mechanism relies on the differential regulation of uptake enzymes and requires a specific operon organization. This organization is found to be conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microorganisms.Keywords
Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (R01GM095903, R01GM095903)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VENI 680-47-419)
- U.S. Department of Health & Human Services | National Institutes of Health
This publication has 61 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Need‐based activation of ammonium uptake in Escherichia coliMolecular Systems Biology, 2012
- Functional and Metabolic Effects of Adaptive Glycerol Kinase (GLPK) Mutants in Escherichia coliJournal of Biological Chemistry, 2011
- Simultaneous consumption of pentose and hexose sugars: an optimal microbial phenotype for efficient fermentation of lignocellulosic biomassApplied Microbiology and Biotechnology, 2010
- Growth Rate-Dependent Global Effects on Gene Expression in BacteriaCell, 2009
- Bioconversion of lignocellulosic biomass: biochemical and molecular perspectivesJournal of Industrial Microbiology & Biotechnology, 2008
- Correlation between Growth Rates, EIIA Crr Phosphorylation, and Intracellular Cyclic AMP Levels in Escherichia coli K-12Journal of Bacteriology, 2007
- Bacterial gene regulation in diauxic and non-diauxic growthJournal of Theoretical Biology, 2007
- How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in BacteriaMicrobiology and Molecular Biology Reviews, 2006
- Reverse Genetics of Escherichia coli Glycerol Kinase Allosteric Regulation and Glucose Control of Glycerol Utilization In VivoJournal of Bacteriology, 2001