Cargando…

Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities

Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae....

Descripción completa

Detalles Bibliográficos
Autores principales: Lao-Martil, David, Verhagen, Koen J. A., Schmitz, Joep P. J., Teusink, Bas, Wahl, S. Aljoscha, van Riel, Natal A. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779790/
https://www.ncbi.nlm.nih.gov/pubmed/35050196
http://dx.doi.org/10.3390/metabo12010074
_version_ 1784637663830081536
author Lao-Martil, David
Verhagen, Koen J. A.
Schmitz, Joep P. J.
Teusink, Bas
Wahl, S. Aljoscha
van Riel, Natal A. W.
author_facet Lao-Martil, David
Verhagen, Koen J. A.
Schmitz, Joep P. J.
Teusink, Bas
Wahl, S. Aljoscha
van Riel, Natal A. W.
author_sort Lao-Martil, David
collection PubMed
description Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented. This review systematically evaluates the literature to describe the current advances, limitations, and opportunities. Different kinetic models have unraveled key kinetic glycolytic mechanisms. Nevertheless, some uncertainties regarding model topology and parameter values still limit the application to specific cases. Progressive improvements in experimental measurement technologies as well as advances in computational tools create new opportunities to further extend the model scale. Notably, models need to be made more complex to consider the multiple layers of glycolytic regulation and external physiological variables regulating the bioprocess, opening new possibilities for extrapolation and validation. Finally, the onset of new data representative of individual cells will cause these models to evolve from depicting an average cell in an industrial fermenter, to characterizing the heterogeneity of the population, opening new and unseen possibilities for industrial fermentation improvement.
format Online
Article
Text
id pubmed-8779790
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87797902022-01-22 Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities Lao-Martil, David Verhagen, Koen J. A. Schmitz, Joep P. J. Teusink, Bas Wahl, S. Aljoscha van Riel, Natal A. W. Metabolites Review Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented. This review systematically evaluates the literature to describe the current advances, limitations, and opportunities. Different kinetic models have unraveled key kinetic glycolytic mechanisms. Nevertheless, some uncertainties regarding model topology and parameter values still limit the application to specific cases. Progressive improvements in experimental measurement technologies as well as advances in computational tools create new opportunities to further extend the model scale. Notably, models need to be made more complex to consider the multiple layers of glycolytic regulation and external physiological variables regulating the bioprocess, opening new possibilities for extrapolation and validation. Finally, the onset of new data representative of individual cells will cause these models to evolve from depicting an average cell in an industrial fermenter, to characterizing the heterogeneity of the population, opening new and unseen possibilities for industrial fermentation improvement. MDPI 2022-01-13 /pmc/articles/PMC8779790/ /pubmed/35050196 http://dx.doi.org/10.3390/metabo12010074 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lao-Martil, David
Verhagen, Koen J. A.
Schmitz, Joep P. J.
Teusink, Bas
Wahl, S. Aljoscha
van Riel, Natal A. W.
Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title_full Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title_fullStr Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title_full_unstemmed Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title_short Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
title_sort kinetic modeling of saccharomyces cerevisiae central carbon metabolism: achievements, limitations, and opportunities
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779790/
https://www.ncbi.nlm.nih.gov/pubmed/35050196
http://dx.doi.org/10.3390/metabo12010074
work_keys_str_mv AT laomartildavid kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities
AT verhagenkoenja kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities
AT schmitzjoeppj kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities
AT teusinkbas kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities
AT wahlsaljoscha kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities
AT vanrielnatalaw kineticmodelingofsaccharomycescerevisiaecentralcarbonmetabolismachievementslimitationsandopportunities