Abstract: The potential mechanism for glutathione oversynthesis in the Saccharomyces cerevisiae mutant Y518 was researched using transcriptome analysis combined with physiological and biochemical characteristics. The results indicated that the rate-limiting enzyme of glutathione synthesis, antioxidant enzymes activities and the expression levels of their encoding genes, and the contents of hydrogen peroxide and nicotinamide adenine dinucleotide phosphate (NADPH) were significantly increased in the mutant whereas pyruvatekinase activity, the contents of pyruvate, citrate and succinate were markedly decreased. Besides, the expression levels of genes involved in the citrate cycle were significantly down-regulated while those involved in the pentose phosphate pathway were significantly up-regulated. Therefore, under endogenous oxidative stress, the mutant might strengthen the synthesis of glutathione by adjusting the activities of rate-limiting enzymes of glutathione synthesis to defend against oxidative stress together with the antioxidant enzymes. Meanwhile, weakened pyruvatekinase activity decreased pyruvate generation, which led to declined citrate cycle flux and increased NADPH production by the pentose phosphate pathway and consequently provided appropriate reducing power for glutathione biosynthesis.

Key words: glutathione, oxidative stress, Saccharomyces cerevisiae, NADPH