基于代谢通量分析的SAM和GSH联产溶氧控制策略

摘要

In order to improve the co-production of SAM and GSH under batch cultivation, the effect of dissolved oxygen (DO) level on fermentative co-production of S-adenosylmethionine (SAM) and glutathione (GSH) in a 5 L stirred fermentor with Candida utilis CCTCC M 209298 was investigated. The metabolic fluxes of intermediates and energy during batch fermentative co-production of SAM and GSH under different agitation rates were calculated by using metabolic flux analysis method. Based on the flux distribution of main intermediates, an optimum DO control strategy of a constant agitation rate of 350 r⋅min−1 maintained during the first 9 h of fermentation followed with a DO level not less than 30% after 9 h was proposed as an efficient approach for high co-production of SAM and GSH. Under this DO control mode, the product of 520.7 mg⋅L−1 for batch co-production of SAM and GSH with C.utilis CCTCC M 209298 was achieved. Furthermore, the reason for the improvement of the co-production of SAM and GSH under the proposed strategy was quantitatively interpreted by the fermentative kinetics, metabolic flux analysis and respiratory quotient, respectively.%　　为了提高S-腺苷甲硫氨酸(SAM)和谷胱甘肽(GSH)的联产量,考察了溶氧条件对Candida utilis CCTCC M 209298发酵联产SAM和GSH的影响.采用代谢通量分析方法对不同转速下SAM和GSH联产发酵过程中的物质和能量代谢进行分析,确定了较优的溶氧控制策略：前9 h的发酵恒定转速350 r⋅min−1,9 h后控制溶氧不低于30%.在此策略下,C. utilis CCTCC M 209298分批发酵生产SAM和GSH的联产量为520.7 mg⋅L−1.最后分别从发酵动力学、代谢通量分析以及呼吸商变化规律对该溶氧控制策略促进SAM和GSH联合高产的原因进行了定量解释.