title: Transcriptome of Saccharomyces cerevisiae during production of D-xylonate.
abstract: BACKGROUND
  Production of D-xylonate by the yeast S. cerevisiae provides an example of bioprocess development for sustainable production of value-added chemicals from cheap raw materials or side streams. Production of D-xylonate may lead to considerable intracellular accumulation of D-xylonate and to loss of viability during the production process. In order to understand the physiological responses associated with D-xylonate production, we performed transcriptome analyses during D-xylonate production by a robust recombinant strain of S. cerevisiae which produces up to 50 g/L D-xylonate.
  
  
  RESULTS
  Comparison of the transcriptomes of the D-xylonate producing and the control strain showed considerably higher expression of the genes controlled by the cell wall integrity (CWI) pathway and of some genes previously identified as up-regulated in response to other organic acids in the D-xylonate producing strain. Increased phosphorylation of Slt2 kinase in the D-xylonate producing strain also indicated that D-xylonate production caused stress to the cell wall. Surprisingly, genes encoding proteins involved in translation, ribosome structure and RNA metabolism, processes which are commonly down-regulated under conditions causing cellular stress, were up-regulated during D-xylonate production, compared to the control. The overall transcriptional responses were, therefore, very dissimilar to those previously reported as being associated with stress, including stress induced by organic acid treatment or production. Quantitative PCR analyses of selected genes supported the observations made in the transcriptomic analysis. In addition, consumption of ethanol was slower and the level of trehalose was lower in the D-xylonate producing strain, compared to the control.
  
  
  CONCLUSIONS
  The production of organic acids has a major impact on the physiology of yeast cells, but the transcriptional responses to presence or production of different acids differs considerably, being much more diverse than responses to other stresses. D-Xylonate production apparently imposed considerable stress on the cell wall. Transcriptional data also indicated that activation of the PKA pathway occurred during D-xylonate production, leaving cells unable to adapt normally to stationary phase. This, together with intracellular acidification, probably contributes to cell death.
authors.affiliation: VTT Technical Research Centre of Finland, P,O, Box 1000, Espoo FI-02044 VTT, Finland. dominik.mojzita@vtt.fi.
authors.forename: Dominik
authors.initials: D
authors.lastname: Mojzita
authors.forename: Merja
authors.initials: M
authors.lastname: Oja
authors.forename: Eija
authors.initials: E
authors.lastname: Rintala
authors.forename: Marilyn
authors.initials: M
authors.lastname: Wiebe
authors.forename: Merja
authors.initials: M
authors.lastname: Penttilä
authors.forename: Laura
authors.initials: L
authors.lastname: Ruohonen
mesh_terms: D002473:Cell Wall / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013312:Stress, Physiological; D013400:Sugar Acids / Q000378:metabolism*; D014994:Xylose / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013400:Sugar Acids; C092647:lyxonic acid; D014994:Xylose; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae