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

Appl Microbiol Biotechnol. 2011 Feb;89(4):1029-37. doi: 10.1007/s00253-010-2946-z. Epub 2010 Oct 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine / metabolism
  • Dipeptides / metabolism
  • Gene Expression Profiling
  • Glutathione / metabolism*
  • Mutation*
  • Proteome / analysis
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / radiation effects
  • Saccharomyces cerevisiae Proteins / analysis
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Analysis, DNA
  • Ultraviolet Rays

Substances

  • Dipeptides
  • Proteome
  • Saccharomyces cerevisiae Proteins
  • Glutathione
  • Cysteine
  • gamma-glutamylcysteine