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Metabolic changes underlying the higher accumulation of glutathione in Saccharomyces cerevisiae mutants

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Abstract

Molecular mechanisms leading to glutathione (GSH) over-accumulation in a Saccharomyces cerevisiae strain produced by UV irradiation-induced random mutagenesis were studied. The mutant accumulated GSH but also cysteine and γ-glutamylcysteine in concentrations that were several fold higher than in its wild-type parent strain under all studied cultivation conditions (chemostat, fed-batch, and turbidostat). Transcript analyses along with shotgun proteome quantification indicated a difference in the expression of a number of genes and proteins, the most pronounced of which were several fold higher expression of CYS3, but also that of GSH1 and its transcriptional activator YAP1. This together with the higher intracellular cysteine concentration is most likely the primary factor underlying GSH over-accumulation in the mutant. Comparative sequencing of GSH1 and the fed-batch experiments with continuous cysteine addition demonstrated that the feedback inhibition of Gsh1p by GSH was still operational in the mutant.

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Acknowledgments

The financial support for this research was provided by the Enterprise Estonia project EU22704, Estonian Ministry of Education and Research grant SF0140090s08, and by Estonian Science Foundation grant G7323. We would like to thank Dr. Chris Powell for critical revision of the manuscript.

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Authors and Affiliations

  1. Competence Centre of Food and Fermentation Technologies, Akadeemia tee 15b, 12618, Tallinn, Estonia

    Ildar Nisamedtinov, Kaspar Kevvai, Kerti Orumets, Liisa Arike & Inga Sarand

  2. Department of Food Processing, Tallinn University of Technology, Tallinn, Estonia

    Ildar Nisamedtinov, Kerti Orumets, Liisa Arike, Inga Sarand & Toomas Paalme

  3. Department of Biosciences, University of Helsinki, Helsinki, Finland

    Matti Korhola

  4. Lallemand, Inc., Montréal, Canada

    Ildar Nisamedtinov

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  1. Ildar Nisamedtinov
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  2. Kaspar Kevvai
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  3. Kerti Orumets
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  4. Liisa Arike
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  7. Toomas Paalme
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Correspondence to Ildar Nisamedtinov.

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Nisamedtinov, I., Kevvai, K., Orumets, K. et al. Metabolic changes underlying the higher accumulation of glutathione in Saccharomyces cerevisiae mutants. Appl Microbiol Biotechnol 89, 1029–1037 (2011). https://doi.org/10.1007/s00253-010-2946-z

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  • DOI: https://doi.org/10.1007/s00253-010-2946-z

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