LAPSE:2023.24958
Published Article
LAPSE:2023.24958
Model Parameterization with Quantitative Proteomics: Case Study with Trehalose Metabolism in Saccharomyces cerevisiae
March 28, 2023
When Saccharomyces cerevisiae undergoes heat stress it stimulates several changes that are necessary for its survival, notably in carbon metabolism. Notable changes include increase in trehalose production and glycolytic flux. The increase in glycolytic flux has been postulated to be due to the regulatory effects in upper glycolysis, but this has not been confirmed. Additionally, trehalose is a useful industrial compound for its protective properties. A model of trehalose metabolism in S. cerevisiae was constructed using Convenient Modeller, a software that uses a combination of convenience kinetics and a genetic algorithm. The model was parameterized with quantitative omics under standard conditions and validated using data collected under heat stress conditions. The completed model was used to show that feedforward activation of pyruvate kinase by fructose 1,6-bisphosphate during heat stress contributes to the increase in metabolic flux. We were also able to demonstrate in silico that overexpression of enzymes involved in production and degradation of trehalose can lead to higher trehalose yield in the cell. By integrating quantitative proteomics with metabolic modelling, we were able to confirm that the flux increase in trehalose metabolic pathways during heat stress is due to regulatory effects and not purely changes in enzyme expression. The overexpression of enzymes involved in trehalose metabolism is a potential approach to be exploited for trehalose production without need for increasing temperature.
Keywords
Genetic Algorithm, heat stress, kinetic model, metabolic engineering, metabolic modelling, trehalose metabolism
Suggested Citation
Yap CF, Garcia-Albornoz M, Jarnuczak AF, Hubbard SJ, Schwartz JM. Model Parameterization with Quantitative Proteomics: Case Study with Trehalose Metabolism in Saccharomyces cerevisiae. (2023). LAPSE:2023.24958
Author Affiliations
Yap CF: Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK; Department of Mathematics, School of Natural Sciences, Faculty of Science and [ORCID]
Garcia-Albornoz M: Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London NW1 [ORCID]
Jarnuczak AF: Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMB [ORCID]
Hubbard SJ: Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Schwartz JM: Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK [ORCID]
Journal Name
Processes
Volume
9
Issue
1
First Page
pr9010139
Year
2021
Publication Date
2021-01-12
Published Version
ISSN
2227-9717
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PII: pr9010139, Publication Type: Journal Article
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LAPSE:2023.24958
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doi:10.3390/pr9010139
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Mar 28, 2023
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