A feed-forward loop guarantees robust behavior in Escherichia coli carbohydrate uptake
Open accessAbstract
Motivation: In Escherichia coli, the phosphoenolpyruvate: carbohydrate phosphotransferase system acts like a sensory element which is able to measure the flux through glycolysis. Since the output of the sensor, the phosphorylated form of protein EIIA, is connected to the activity of the global transcription factor Crp, the kinetic and structural properties of the system are important for the understanding of the overall cellular behavior. Results: A family of mathematical models is presented, varying with respect to their degree of complexity (number of reactions that are taken into account, number of parameters) that show a structurally and quantitatively robust behavior. The models describe a set of experimental data that relates the output of the sensor to the specific growth rate. A central element that is responsible for the structural robustness is a feed-forward loop in the glycolysis, namely the activation of the pyruvate kinase reaction by a metabolite of the upper part of the glycolysis. The robustness is shown for variations of the measured data as well as for variations of the parameters. Availability: MATLAB files for model simulations are available on http://www.mpi-magdeburg.mpg.de/people/kre/robust/ A short description of the files provided on this site can be found in the Supporting information. Contact: kremling@mpi-magdeburg.mpg.de
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Existing constraint-based models with Boolean regulatory architecture assume a rigid, positive correlation between metabolic flux and metabolite levels, neglecting that this correlation can also be negative and nuanced.
“Specifically, these models assume a rigid, positive correlation between metabolic flux and metabolite levels (neglecting the fact that this correlation can also be negative, see Kremling et al (2008), and nuanced, see below).”
From Bacterial adaptation through distributed sensing of metabolic fluxes (2010) · cites this paper as Kremling et al (2008)
The fast switch is formed by PEP and FBP mutually activating each other's consuming enzymes (Fdp, PykF, Ppc) through feed-forward loops, a motif that enables a high level of the upstream metabolite to lower the level of the downstream metabolite.
“The fast switch is formed by PEP and FBP mutually activating each other's consuming enzymes (Fdp, PykF, Ppc) through feed-forward loops, a motif that enables a high level of the upstream metabolite to lower the level of the downstream metabolite (Kremling et al, 2008).”
From Bacterial adaptation through distributed sensing of metabolic fluxes (2010) · cites this paper as Kremling et al, 2008
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Bacterial adaptation through distributed sensing of metabolic fluxes
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- Authors
- Kremling, A., Bettenbrock, K., & Gilles, E. D.
- Affiliations
- Max Planck Institute for Dynamics of Complex Technical Systems (DE)
- Corresponding author
- Kremling, A.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-10
- Volume
- 24
- Issue
- 5
- Pages
- 704-710
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- OpenAlex
- W2146206624
- Cited by
- 45
- References
- 20
- Citations by year
- 2025: 1 · 2024: 2 · 2021: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 9
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- feed-forward loop, structural robustness, Escherichia coli, carbohydrate absorption, phosphoenolpyruvate:carbohydrate phosphotransferase system, glycolysis, mathematical modeling, parameter sensitivity, specific growth rate
- MeSH terms
- Escherichia coli, Kinetics, Models, Theoretical, Carbohydrate Metabolism
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