Dynamic flux balance analysis of the metabolism of Saccharomyces cerevisiae during the shift from fully respirative or respirofermentative metabolic states to anaerobiosis

Paula Jouhten*, Marilyn Wiebe, Merja Penttila

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Dynamic flux balance analysis was utilized to simulate the metabolic behaviour of initially fully respirative and respirofermentative steady-state cultures of Saccharomyces cerevisiae during sudden oxygen depletion. The hybrid model for the dynamic flux balance analysis included a stoichiometric genome-scale metabolic model as a static part and dynamic equations for the uptake of glucose and the cessation of respirative metabolism. The yeast consensus genome-scale metabolic model [Herrgard MJ et al. (2008) Nat Biotechnol 26, 1155-1160; Dobson PD et al. (2010) BMC Syst Biol 4, 145] was refined with respect to oxygen-dependent energy metabolism and further modified to reflect S. cerevisiae anabolism in the absence of oxygen. Dynamic flux balance analysis captured well the essential features of the dynamic metabolic behaviour of S. cerevisiae during adaptation to anaerobiosis. Modelling and simulation enabled the identification of short time-scale flux distribution dynamics under the transition to anaerobic metabolism, during which the specific growth rate was reduced, as well as longer time-scale process dynamics when the specific growth rate recovered. Expression of the metabolic genes was set into the context of the identified dynamics. Metabolic gene expression responses associated with the specific growth rate and with the cessation of respirative metabolism were distinguished.

Original languageEnglish
Pages (from-to)3338-3354
Number of pages17
JournalFEBS Journal
Volume279
Issue number18
DOIs
Publication statusPublished - Sept 2012
MoE publication typeA1 Journal article-refereed

Keywords

  • dynamic flux balance analysis
  • metabolism
  • modelling
  • oxygen
  • Saccharomyces cerevisiae
  • ESCHERICHIA-COLI
  • ETHANOL-PRODUCTION
  • STEADY-STATE
  • GROWTH-RATE
  • TRANSCRIPTIONAL RESPONSE
  • CELLULAR-METABOLISM
  • CHEMOSTAT CULTURES
  • ELECTRON-TRANSFER
  • SYSTEMS BIOLOGY
  • GENE-EXPRESSION

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