Salt-induced osmotic stress for glutathione overproduction in Candida utilis

The effect of NaCl-induced osmotic stress on glutathione (GSH) production was investigated in Candida utilis. Based on the fact that NaCl stress can enhance GSH production but inhibit cells growth simultaneously, the novel strategies of multiple osmotic stresses with different NaCl additions (0.2 mol/l at 4 h, 0.4 mol/l at 8 h, and 0.6 mol/l at 12 and 16 h) were developed for GSH overproduction. After 30 h cultivation, GSH yield reached 238 mg/l and intracellular GSH content was 2.34%, increased by 66.4% and 70.7% respectively compared to the control. Further applying the strategies to 7 l fermentor, GSH yield of 356 mg/l was achieved at 30 h, which was 65.6% higher than the control. Moreover, NaCl stress led to an increase in intracellular cysteine content and activities of γ-glutamylcysteine synthetase, GSH synthetase and GSH reductase, explaining the mechanism involved in inducing cellular GSH accumulation.