Abstract:

The effect of pH on glutathione production was investigated in batch culture of Candida utilis SZU 07-01 in this study, pH3.5 and pH1.5 were determined as mild acid stress and severe acid stress conditions, respectively, based on analyzing and comparing the process parameters. Optimal time of 6 h and 2 h for mild acid stress of pH3. 5 and severe acid stress of pH1. 5 were then chosen for glutathione overproduction, respectively, during continuous culture of C.utilis SZU 07-01 in a chemostat.  Furthermore, C.utilis SZU 07-01 was cultured under batch culture with glucose feeding and acid stress, it was found that mild acid stress for 6 h was more advantageous to glutathione overproduction than severe acid stress for 2 h and no acid stress. In the end, the mechanisms of glutathione overproduction by mild acid stress were quantitatively interpreted by comparison of parameters obtained from batch fermentation kinetics, intracellular cofactors as NADH and ATP, together with the distribution of flux on key metabolites within glutathione biosynthesis.

摘要：

以产朊假丝酵母Candida utilis SZU 07-01产谷胱甘肽（GSH）为研究对象，分析比较了恒定pH和不控制pH条件下GSH的分批发酵过程，确定pH3.5和pH1.5分别为弱酸胁迫和强酸胁迫条件。通过对C.utilis SZU 07-01恒化培养过程进行分析，选择合适的酸胁迫时间分别为弱酸胁迫6 h和强酸胁迫2 h。采用分批补料培养方式，比较了不同酸胁迫条件下的GSH生物合成情况，发现长时间弱酸胁迫比短时间强酸胁迫和不胁迫更有利于GSH的过量合成。最后，分别从分批发酵动力学、胞内辅因子（NADH、ATP）以及各关键代谢物的代谢通量变化规律等角度对弱酸胁迫促进GSH过量合成的机理进行了定量分析。