Background Glutathione is an important bioactive tripeptide and is widely used in the food, medicine, and cosmetics industries. The aim of this study was to provide an efficient method for producing GSH and to explore its synthesis mechanism. Saccharomyces cerevisiae strain HBSD-W08 was screened for GSH production, and its fermentation medium was optimized using single-factor experiments of the Plackett-Burman and central composite rotatable designs. This method was used to analyze the effects of the presence and concentration of various carbon sources, organic and inorganic nitrogen sources, metal ions, and precursor amino acids on GSH production and catalase, superoxide dismutase, and γ-glutamylcysteine synthetase activity. Results The three most significant factors affecting GSH production were peptone (optimal concentration [OC]: 2.50 g L− 1), KH2PO4 (OC: 0.13 g L− 1), and glutamic acid (OC: 0.10 g L− 1). GSH productivity of HBSD-W08 was obtained at 3.70 g L− 1 in the optimized medium. The activity of γ-GCS, which is a marker for oxidative stress, was found to be highly positively correlated with GSH production. Conclusions This finding revealed an underlying relationship between GSH synthesis and oxidative stress, providing useful information for developing effective GSH fermentation control strategies.

Background Glutathione (GSH) is an important bioactive tripeptide and is widely used in the food, medicine, and cosmetics industries. The aim of this study was to provide an efficient method for producing GSH and to explore its synthesis mechanism. Saccharomyces cerevisiae strain HBSD-W08 was screened for GSH production, and its fermentation medium was optimized using single-factor experiments of the Plackett-Burman and central composite rotatable designs. This method was used to analyze the effects of the presence and concentration of various carbon sources, organic and inorganic nitrogen sources, metal ions, and precursor amino acids on GSH production and catalase (CAT), superoxide dismutase (SOD), and γ-glutamylcysteine synthetase (γ-GCS) activity. Results The three most significant factors affecting GSH production were peptone (optimal concentration [OC]: 2.50 g L− 1), KH2PO4 (OC: 0.13 g L− 1), and glutamic acid (OC: 0.10 g L− 1). GSH productivity of HBSD-W08 was obtained at 3.70 g L− 1 in the optimized medium. The activity of γ-GCS, which is a marker for oxidative stress, was found to be highly positively correlated with GSH production. Conclusions This finding revealed an underlying relationship between GSH synthesis and oxidative stress, providing useful information for developing effective GSH fermentation control strategies.