Cited by 147Microbial Metabolic Engineering and BioproductionGene Regulatory Network AnalysisFungal and yeast genetics research

A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes

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Smallbone, Kieran, Messiha, Hanan L., Carroll, Kathleen M., Winder, Catherine L., Malys, Naglis, Dunn, Warwick B., Murabito, Ettore, Swainston, Neil +17 more·2013·FEBS Letters

Abstract

We present an experimental and computational pipeline for the generation of kinetic models of metabolism, and demonstrate its application to glycolysis in Saccharomyces cerevisiae . Starting from an approximate mathematical model, we employ a “cycle of knowledge” strategy, identifying the steps with most control over flux. Kinetic parameters of the individual isoenzymes within these steps are measured experimentally under a standardised set of conditions. Experimental strategies are applied to establish a set of in vivo concentrations for isoenzymes and metabolites. The data are integrated into a mathematical model that is used to predict a new set of metabolite concentrations and reevaluate the control properties of the system. This bottom‐up modelling study reveals that control over the metabolic network most directly involved in yeast glycolysis is more widely distributed than previously thought.

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  1. [25]van Hoek P. de Hulster E. van Dijken J.P. Pronk J.T. Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast Biotechnol. Bioeng. 68 2000 517 523 10797237
  2. [74]Lebioda L. Stec B. Mechanism of enolase: the crystal structure of enolase-Mg2+-2-phosphoglycerate/phosphoenolpyrvate complex resolution Biochemistry 30 1991 2817 2822 2007120

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Authors
Smallbone, K., Messiha, H. L., Carroll, K. M., Winder, C. L., Malys, N., Dunn, W. B., Murabito, E., Swainston, N., Dada, J. O., Khan, F., Pir, P., Simeonidis, E., Spasić, I., Wishart, J., Weichart, D., Hayes, N. W., Jameson, D., Broomhead, D. S., Oliver, S. G., Gaskell, S. J., McCarthy, J. E. G., Paton, N. W., Westerhoff, H. V., Kell, D. B., & Mendes, P.
Affiliations
  • University of Manchester (GB)
  • Manchester Academic Health Science Centre (GB)
  • Babraham Institute (GB)
  • University of Luxembourg (LU)
  • University of Exeter (GB)
  • University of Cambridge (GB)
  • Queen Mary University of London (GB)
Corresponding author
Mendes, Pedro
Venue
FEBS Letters
Publisher
Wiley
Published
2013-07-03
Volume
587
Issue
17
Pages
2832-2841
ISSN
  • 0014-5793 (ISSN-L)
  • 1873-3468
OpenAlex
W2149741353
Cited by
147
References
88
Citations by year
2026: 10 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 18 · 2021: 12 · 2020: 11 · 2019: 9 · 2018: 11 · 2017: 21 · 2016: 8 · 2015: 16 · 2014: 11 · 2013: 2
FWCI
5.52
Type
journal article
Language
en
Open access
Locations
  • FEBS Letters (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • MIMS EPrints (University of Southampton) (acceptedVersion)
  • Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
  • Research Explorer (The University of Manchester) (submittedVersion, cc-by-nc-nd)
  • KTUePubl (Repository of Kaunas University of Technology) (submittedVersion, other-oa)
  • UvA-DARE (University of Amsterdam) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
  • VU Research Portal (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • BBSRC (BB/J019259/1)
  • EPSRC (BB/C008219/1)
  • The Manchester Centre for Integrative Systems Biology (MCISB)
  • EU FP7 (KBBE) (289434)
  • BioPreDyn
  • NIH (R01 GM080219)
  • Manchester Centre for Integrative Systems Biology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
yeast glycolysis, Saccharomyces cerevisiae, enzyme kinetic parameters, isozymes, flux control, bottom-up modeling
MeSH terms
Computer Simulation, Glycolysis, Isoenzymes, Kinetics, Models, Biological, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Systems Biology, Metabolic Networks and Pathways

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