Applied Microbiology and Biotechnology

, Volume 77, Issue 4, pp 763–769 | Cite as

Influence of culture conditions on glutathione production by Saccharomyces cerevisiae

  • Lucielen Oliveira Santos
  • Tatiane Araujo Gonzales
  • Beatriz Torsani Úbeda
  • Ranulfo Monte Alegre
Biotechnological Products and Process Engineering


A strategy of experimental design using a fractional factorial design (FFD) and a central composite rotatable design (CCRD) were carried out with the aim to obtain the best conditions of temperature (20–30°C), agitation rate (100–300 rpm), initial pH (5.0–7.0), inoculum concentration (5–15%), and glucose concentration (30–70 g/l) for glutathione (GSH) production in shake-flask culture by Saccharomyces cerevisiae ATCC 7754. By a FFD (25–2), the agitation rate, temperature, and pH were found to be significant factors for GSH production. In CCRD (22) was obtained a second-order model equation, and the percent of variation explained by the model was 95%. The results showed that the optimal culture conditions were agitation rate, 300 rpm; temperature, 20°C; initial pH, 5; glucose, 54 g/l; and inoculum concentration, 5%. The highest GSH concentration (154.5 mg/l) was obtained after 72 h of fermentation.


Glutathione Saccharomyces cerevisiae Culture optimization Experimental design 



The authors would like to thank the financial support from The National Council for Scientific and Technological Development (CNPq) of Brazil.


  1. Alfafara C, Miura K, Shimizu H, Shioya S, Suga K (1992) Cysteine addition strategy for maximum glutathione production in fed-batch of Saccharomyces cerevisiae. Appl Microbiol Biotechnol 37:141–146CrossRefGoogle Scholar
  2. Cha J, Park J, Jeon B, Lee Y, Cho Y (2004) Optimal fermentation conditions for enhanced glutathione production by Saccharomyces cerevisiae FF-8. J Microbiol 42:51–55Google Scholar
  3. Katapodis P, Christakopoulou V, Kekos D, Christakopoulos P (2007) Optimization of xylanase production by Chaetomium thermophilum in wheat straw using response surface methodology. Biochem Eng J 35:136–141CrossRefGoogle Scholar
  4. Li Y, Chen J, Mao Y, Lun S, Koo Y (1998) Effect of additives and fed-batch culture strategies on the production of glutathione by recombinant Escherichia coli. Process Biochem 33:709–714CrossRefGoogle Scholar
  5. Li Y, Wei G, Chen J (2004) Glutathione: a review on biotechnological production. Appl Microbiol Biotechnol 66:233–242CrossRefGoogle Scholar
  6. Li Y, Hugenholtz J, Sybesma W, Abee T, Molenaar D (2005) Using Lactococcus lactis for glutathione overproduction. Appl Microbiol Biotechnol 67:83–90CrossRefGoogle Scholar
  7. Liu C, Hwang C, Liao C (1999) Medium optimization for glutathione production by Saccharomyces cerevisiae. Process Biochem 34:17–23CrossRefGoogle Scholar
  8. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 53:711–760CrossRefGoogle Scholar
  9. Owens CWI, Belcher RV (1965) A colorimetric micro-method for the determination of glutathione. Biochem J 94:705–711Google Scholar
  10. Rollini M, Manzoni M (2006) Influence of different fermentation parameters on glutathione volumetric productivity by Saccharomyces cerevisiae. Process Biochem 41:1501–1505CrossRefGoogle Scholar
  11. Sakato K, Tanaka H (1992) Advanced control of glutathione fermentation process. Biotechnol Bioeng 40:904–912CrossRefGoogle Scholar
  12. Wei G, Li Y, Du G, Chen J (2003a) Effect of surfactants on extracellular accumulation of glutathione by Saccharomyces cerevisiae. Process Biochem 38:1133–1138CrossRefGoogle Scholar
  13. Wei G, Li Y, Du G, Chen J (2003b) Application of two-stage temperature control strategy for enhanced glutathione production in the batch fermentation by Candida utilis. Biotechnol Lett 25:887–890CrossRefGoogle Scholar
  14. Wen S, Zhang T, Tan T (2004) Utilization of amino acids to enhance glutathione production in Saccharomyces cerevisiae. Enzyme Microb Technol 35:501–507CrossRefGoogle Scholar
  15. Wen S, Zhang T, Tan T (2005) Optimization of the amino acid composition in glutathione fermentation. Process Biochem 40:3474–3479CrossRefGoogle Scholar
  16. Wu G, Fang Y, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492Google Scholar
  17. Zhang T, Wen S, Tan T (2007) Optimization of the medium for glutathione production in Saccharomyces cerevisiae. Process Biochem 42:454–458CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Lucielen Oliveira Santos
    • 1
  • Tatiane Araujo Gonzales
    • 1
  • Beatriz Torsani Úbeda
    • 1
  • Ranulfo Monte Alegre
    • 1
  1. 1.Department of Food Engineering, College of Food EngineeringUNICAMP (State University of Campinas)CampinasBrazil

Personalised recommendations