High-Cell-Density Fermentation For S-Adenosyl-L-Methionine Production

S-adenosyl-L-methionine(SAM) is an important small molecule in all living organisms, and has great pharmaceutical effect on liver disease and psychopathy. Although China has a great many patients with the diseases, it has not been industrialized in China. Based on previous studies, high-cell-density fermentation technique was successfully applied to SAM production.The accumulation of SAM by several Saccharomyces cerevisiaes was compared. And the Saccharomyces cerevisiae Q5has the highest yield of SAM which could reach561mg·L-1. The growth curve of Q5strain was investigated. And the optimum temperature and pH of the growth and biosynthesis were also investigated.The pre-L-methionine was one of the key factors of SAM production. The effects that feeding strategies and the amount of precursor L-methionine had on the production of SAM were investigated. In our work, it was found that total amount of L-methionine added should be no less than0.7g per10grams of dry cell weight. Five different feeding strategies had been investigated in our experiment, and such comparison indicated that favorable results could be achieved as the biomass reached the status of high cell density (120g·L-1). Maximum yield of4.98g·L-1and over130g·L-1of biomass was gained.The influences of relevant12amino acids on SAM production were investigated. The results showed that L-cystine, L-cysteine, L-lysine, L-histidine, L-methionine could enhance the yield of SAM. Three different feeding strategies were studied in our experiments. And their amounts were1g·L-1,1g·L-1,1.5g·L-1,1g·L-1,1g·L-1respectively according to the orthogonal matrix method. Experiment on5L fermenter revealed that the accumulation of SAM could reach5.53g·L-1, and128g·L-1of biomass could be obtained.The effects of metal ions on SAM production were studied. Though five different metal ions comparison, it was found that Cu2+and Ca2+had positive effects of biomass and SAM production. And the results showed their optimum amounts were150ppm and100ppm respectively.