Controlling glucose feeding rate, according to the change of ethanol concentration and respiratory quotient (RQ), has been studied in high-cell-density cultivation of Saccharomyces cerevisiae for glutathione (GSH). GSH yield and dry cell weight reached 1620 mg/L and 140 g/L, respectively, after 52 h of cultivation. In addition, optimized single shot addition of precursor amino acids (performed in both flask and fermentor experiments) at 32 h could result in the GSH yield reached 2020 mg/L after 38 It of cultivation. The yield and productivity of GSH increased 25% and 70%, respectively. Moreover, cultivation time was reduced to 38 h, compared with results without adding the precursor amino acids. (c) 2006 Elsevier Ltd. All rights reserved.