Abstract: The effect of different pH conditions on the biosynthesis of S-adenosylmethionine (SAM) and glutathione (GSH) by Candida utilis under high cell density culture was investigated. Moderate acid stress (pH 3.5) was found to be beneficial for SAM and GSH biosynthesis and consequently the high-yield co-production of SAM and GSH by the yeast cells. By measuring the key enzymes activities, energy supply, and the intracellular redox environment, moderate acid stress was shown to be able to increase the activities of SAM synthase, γ-glutamylcysteine synthase, hexokinase, ATP synthase and catalase, and elevate the intracellular levels and regeneration abilities of NADH and ATP, thereby ensuring sufficient substance and energy supply for the over-production of SAM and GSH. Results obtained in this study present adequate evidence to reveal the physiological mechanism of moderate acid stress in improving SAM and GSH biosynthesis, which may provide a feasible idea for the over-production of other similar small molecular bioactive compounds.

Key words: Candida utilis, S-adenosylmethionine, glutathione, co-production, acid stress