An effective strategy for the co-production of S-adenosyl-L-methionine and glutathione by fed-batch fermentation

摘要

Both S-adenosyl-L-methionine (SAM) and glutathione (GSH) are intracellular molecules with important physiological activities and medical applications.The metabolic pathways of SAM and GSH in yeast cell are tightly connected,which leads us to develop a new strategy to produce them jointly.The aim of this work is to maximize the co-production of SAM and GSH simultaneously by high cell density culture of baker's yeast.A strategy of two-stage fed-batch culture was developed to optimize the production.The first exponential feeding stage was aimed to reduce the formation of ethanol and to increase the cell density.For this purpose,the initial medium composition was modified to fit the high cell-density cultivation of yeast.With the modified media,the final concentration of SAM,GSH and cells obtained in experiment were increased to 8.77,0.81 and 105 g/L,respectively.Meanwhile,the yields of SAM and GSH on glucose reached 0.039 and 0.0035 g/g,respectively,which were still relatively low due to the fermentative consumption of glucose.To enhance the yields,a constant feeding stage during the transformation phase was performed to satisfy the energy and precursor requirement for the synthesis of SAM and GSH with the absence of ethanol formation.Due to the elimination of ethanol production,the yields of SAM and GSH on glucose were enhanced up to 0.048 and 0.0038 g/g,respectively.