Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures

Research output: Contribution to journalArticle

Researchers

  • Susanne Alff-Tuomala
  • Laura Salusjärvi
  • Dorothee Barth
  • Merja Oja
  • Merja Penttilä

  • Juha-Pekka Pitkänen
  • Laura Ruohonen
  • Paula Jouhten

Research units

  • VTT Technical Research Centre of Finland

Abstract

Xylose is present with glucose in lignocellulosic streams available for valorisation to biochemicals. Saccharomyces cerevisiae has excellent characteristics as a host for the bioconversion, except that it strongly prefers glucose to xylose, and the co-consumption remains a challenge. Further, since xylose is not a natural substrate of S. cerevisiae, the regulatory response it induces in an engineered strain cannot be expected to have evolved for its utilisation. Xylose-induced effects on metabolism and gene expression during anaerobic growth of an engineered strain of S. cerevisiae on medium containing both glucose and xylose medium were quantified. The gene expression of S. cerevisiae with an XR-XDH pathway for xylose utilisation was analysed throughout the cultivation: at early cultivation times when mainly glucose was metabolised, at times when xylose was co-consumed in the presence of low glucose concentrations, and when glucose had been depleted and only xylose was being consumed. Cultivations on glucose as a sole carbon source were used as a control. Genome-scale dynamic flux balance analysis models were simulated to analyse the metabolic dynamics of S. cerevisiae. The simulations quantitatively estimated xylose-dependent flux dynamics and challenged the utilisation of the metabolic network. A relative increase in xylose utilisation was predicted to induce the bi-directionality of glycolytic flux and a redox challenge even at low glucose concentrations. Remarkably, xylose was observed to specifically delay the glucose-dependent repression of particular genes in mixed glucose-xylose cultures compared to glucose cultures. The delay occurred at a cultivation time when the metabolic flux activities were similar in the both cultures.

Details

Original languageEnglish
Pages (from-to)969-985
Number of pages17
JournalApplied Microbiology and Biotechnology
Volume100
Issue number2
Publication statusPublished - Jan 2016
MoE publication typeA1 Journal article-refereed

    Research areas

  • Metabolic modelling, Saccharomyces cerevisiae, Xylose, Gene expression, Anaerobic, PENTOSE-PHOSPHATE PATHWAY, FLUX BALANCE ANALYSIS, TRANSCRIPTIONAL REGULATION, ETHANOL-PRODUCTION, PICHIA-STIPITIS, XYLITOL-DEHYDROGENASE, SYSTEMS BIOLOGY, FUNCTIONAL EXPRESSION, ESCHERICHIA-COLI, OXIDATIVE STRESS

ID: 9225230