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

  • Bioenergy and Biofuels
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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.

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Acknowledgments

We wish to thank Stefan Bruder for his help in the wet-lab work of the gene expression analysis and Sami Holmström for his help in the analysis of cultivation samples. We thank Dr. Marilyn Wiebe for the valuable comments on the study. Heidi Turkia is thanked for measuring the minor acid concentrations. Additionally, Dr. Maurizio Bettiga from Chalmers University of Technology, Sweden, is thanked for curing VTT C-10880 for its uracil auxotrophy.

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  1. Paula Jouhten

    Present address: EMBL, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117, Heidelberg, Germany

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  1. VTT Technical Research Centre of Finland Ltd, P.O. Box 1000, 02044 VTT, Espoo, Finland

    Susanne Alff-Tuomala, Laura Salusjärvi, Dorothee Barth, Merja Oja, Merja Penttilä, Juha-Pekka Pitkänen, Laura Ruohonen & Paula Jouhten

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  5. Merja Penttilä
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  8. Paula Jouhten
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Corresponding author

Correspondence to Paula Jouhten.

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Research did not involve any human participants or animals.

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The authors declare that they have no conflict of interest.

Funding

The research has received funding from the European Commission, the Seventh Framework Programme (FP7/2007-2013) under the project NEMO (grant agreement no. 222699). PJ acknowledges funding from the Academy of Finland for a Postdoctoral research (grant 140380).

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Alff-Tuomala, S., Salusjärvi, L., Barth, D. et al. Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures. Appl Microbiol Biotechnol 100, 969–985 (2016). https://doi.org/10.1007/s00253-015-7038-7

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  • DOI: https://doi.org/10.1007/s00253-015-7038-7

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