Novel pH control strategy for glutathione overproduction in batch cultivation of Candida utilis

The effects of pH values on cell growth and glutathione (GSH) production were studied in batch cultivation of Candida utilis. According to the fact that lower pH value favors cells growth but retards GSH production and higher pH value promotes GSH production while inhibits cells growth, a pH-shift strategy, optimized via simulating Gauss function, was developed. By applying two-stage pH-shift strategy of controlling pH at 5.0 for first 7.5 h and switching to 6.0 afterwards, final GSH yield and productivity reached 279 and 12.7 mg/l/h after 22 h cultivation, increased by 30 and 42%, respectively, compared to constant pH 5.5 operation. Moreover, by feeding glucose instead of sulphuric acid (H2SO4) solution to control pH, maximal GSH yield of 315 mg/l was achieved, suggesting application of pH-shift strategy for GSH overproduction as being feasible.