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A computational toolbox to investigate the metabolic potential and resource allocation in fission yeast

View ORCID ProfilePranas Grigaitis, Douwe A. J. Grundel, Eunice van Pelt-Kleinjan, Mirushe Isaku, Guixiang Xie, Sebastian Mendoza Farias, View ORCID ProfileBas Teusink, View ORCID ProfileJohan H. van Heerden
doi: https://doi.org/10.1101/2022.05.04.490403
Pranas Grigaitis
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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  • ORCID record for Pranas Grigaitis
  • For correspondence: p.grigaitis@vu.nl j.van.heerden@vu.nl
Douwe A. J. Grundel
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
2Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747AG Groningen, the Netherlands
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Eunice van Pelt-Kleinjan
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
3TiFN, P.O. Box 557, 6700AN Wageningen, the Netherlands
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Mirushe Isaku
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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Guixiang Xie
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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Sebastian Mendoza Farias
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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Bas Teusink
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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Johan H. van Heerden
1Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, the Netherlands
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  • ORCID record for Johan H. van Heerden
  • For correspondence: p.grigaitis@vu.nl j.van.heerden@vu.nl
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Abstract

The fission yeast Schizosaccharomyces pombe is a popular eukaryal model organism for cell division and cell cycle studies. With this extensive knowledge of its cell and molecular biology, S. pombe also holds promise for use in metabolism research and industrial applications. However, unlike the baker’s yeast Saccharomyces cerevisiae, a major workhorse in these areas, cell physiology and metabolism of S. pombe remain less explored. One way to advance understanding of organism-specific metabolism is construction of computational models and their use for hypothesis testing. To this end, we leverage existing knowledge of S. cerevisiae to generate a manually-curated high-quality reconstruction of S. pombe’s metabolic network, including a proteome-constrained version of the model. Using these models, we gain insights into the energy demands for growth, as well as ribosome kinetics in S. pombe. Furthermore, we predict proteome composition and identify growth-limiting constraints that determine optimal metabolic strategies under different glucose availability regimes, and reproduce experimentally determined metabolic profiles. Notably, we find similarities in metabolic and proteome predictions of S. pombe with S. cerevisiae, which indicate that similar cellular resource constraints operate to dictate metabolic organization. With these use cases, we show, on the one hand, how these models provide an efficient means to transfer metabolic knowledge from a well-studied to a lesser-studied organism, and on the other, how they can successfully be used to explore the metabolic behaviour and the role of resource allocation in driving different strategies in fission yeast.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 04, 2022.
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A computational toolbox to investigate the metabolic potential and resource allocation in fission yeast
Pranas Grigaitis, Douwe A. J. Grundel, Eunice van Pelt-Kleinjan, Mirushe Isaku, Guixiang Xie, Sebastian Mendoza Farias, Bas Teusink, Johan H. van Heerden
bioRxiv 2022.05.04.490403; doi: https://doi.org/10.1101/2022.05.04.490403
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A computational toolbox to investigate the metabolic potential and resource allocation in fission yeast
Pranas Grigaitis, Douwe A. J. Grundel, Eunice van Pelt-Kleinjan, Mirushe Isaku, Guixiang Xie, Sebastian Mendoza Farias, Bas Teusink, Johan H. van Heerden
bioRxiv 2022.05.04.490403; doi: https://doi.org/10.1101/2022.05.04.490403

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