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  • Li, Gang,1991Chalmers tekniska högskola,Chalmers University of Technology (author)

Bayesian genome scale modelling identifies thermal determinants of yeast metabolism

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-01-08
  • Springer Science and Business Media LLC,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:research.chalmers.se:439d91c5-f270-4244-af05-9a7acf862b9a
  • https://doi.org/10.1038/s41467-020-20338-2DOI
  • https://research.chalmers.se/publication/521980URI
  • https://gup.ub.gu.se/publication/304006URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • The molecular basis of how temperature affects cell metabolism has been a long-standing question in biology, where the main obstacles are the lack of high-quality data and methods to associate temperature effects on the function of individual proteins as well as to combine them at a systems level. Here we develop and apply a Bayesian modeling approach to resolve the temperature effects in genome scale metabolic models (GEM). The approach minimizes uncertainties in enzymatic thermal parameters and greatly improves the predictive strength of the GEMs. The resulting temperature constrained yeast GEM uncovers enzymes that limit growth at superoptimal temperatures, and squalene epoxidase (ERG1) is predicted to be the most rate limiting. By replacing this single key enzyme with an ortholog from a thermotolerant yeast strain, we obtain a thermotolerant strain that outgrows the wild type, demonstrating the critical role of sterol metabolism in yeast thermosensitivity. Therefore, apart from identifying thermal determinants of cell metabolism and enabling the design of thermotolerant strains, our Bayesian GEM approach facilitates modelling of complex biological systems in the absence of high-quality data and therefore shows promise for becoming a standard tool for genome scale modeling.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Hu, Yating,1991Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)yating (author)
  • Zrimec, Jan,1981Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)zrimec (author)
  • Luo, Hao,1992Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)lhao (author)
  • Wang, Hao,1975Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine(Swepub:gu)xwangh (author)
  • Zelezniak, Aleksej,1984Science for Life Laboratory (SciLifeLab),Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)alezel (author)
  • Ji, Boyang,1983Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)bojand (author)
  • Nielsen, Jens B,1962Danmarks Tekniske Universitet,Technical University of Denmark,BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (author)
  • Chalmers tekniska högskolaWallenberg Centre for Molecular and Translational Medicine (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Science and Business Media LLC12:12041-17232041-1723

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