Applied Microbiology and Biotechnology

, Volume 96, Issue 4, pp 1021–1027 | Cite as

Extracellular glutathione fermentation using engineered Saccharomyces cerevisiae expressing a novel glutathione exporter

  • Kentaro Kiriyama
  • Kiyotaka Y. Hara
  • Akihiko Kondo
Applied microbial and cell physiology


A novel extracellular glutathione fermentation method using engineered Saccharomyces cerevisiae was developed by following three steps. First, a platform host strain lacking the glutathione degradation protein and glutathione uptake protein was constructed. This strain improved the extracellular glutathione productivity by up to 3.2-fold compared to the parental strain. Second, the ATP-dependent permease Adp1 was identified as a novel glutathione export ABC protein (Gxa1) in S. cerevisiae based on the homology of the protein sequence with that of the known human glutathione export ABC protein (ABCG2). Overexpression of this GXA1 gene improved the extracellular glutathione production by up to 2.3-fold compared to the platform host strain. Finally, combinatorial overexpression of the GXA1 gene and the genes involved in glutathione synthesis in the platform host strain increased the extracellular glutathione production by up to 17.1-fold compared to the parental strain. Overall, the metabolic engineering of the glutathione synthesis, degradation, and transport increased the total (extracellular + intracellular) glutathione production. The extracellular glutathione fermentation method developed in this study has the potential to overcome the limitations of the present intracellular glutathione fermentation process in yeast.


Extracellular glutathione production Glutathione transport Yeast ABC protein Cell factory 


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Kentaro Kiriyama
    • 1
  • Kiyotaka Y. Hara
    • 2
  • Akihiko Kondo
    • 1
  1. 1.Department of Chemical Science and Engineering, Graduate School of EngineeringKobe UniversityNada-kuJapan
  2. 2.Organization of Advanced Science and TechnologyKobe UniversityNada-kuJapan

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