| S-Adenosyl-L-Methionine (SAM) is an important in-vivo metabolic intermediate and is involved in several tens kinds of metabolic reactions. Since it was placed on the European market in late 1970's, the more and more pharmacology of SAM had been defined. The indications of SAM have been widely expanded, which include anti-inflammatory and analgesic, anti-depression, prevention and treatment of liver disease. The latter two have contributed a lot to the improvement of the prevention and treatment of depression and hepatopathy in China currently. Although SAM has been applied to clinical for several decades, the production process of it still base on fermentation of the yeast heretofore. Owing to the progress of enzyme engineering technology, it is possible for us to synthesize SAM in large scale by enzymatic reaction nowadays. As enzymatic reaction is high efficient and strong selectivity, it can get over many shortages of the traditional process, such as overlong operational cycle, low concentration of the target material in fermentation broth, high possibility of racemization of the product and big challenge of environmental protection, so that achieving a new production process with high efficiency and low cost.This research is a pilot plant testing on the basis of experience of bench scale experiment. It mainly focuses on the following points.①Optimization of the fermentation of Escherichia Coli.②Extraction and purification of the enzyme.③Scale up and optimize enzymatic reaction.④Concentrating large-scale refined solution by nano-filtration.⑤Lyophilization of the concentrated solution.In this research, the volumes of fermentation and enzymatic reaction have reached 1500L, the maximal volume of concentration is 1000L, and 20.1kg drug substance is obtained. The drug substance, with correct salification, has high content of not less than 98%, low impurity content of not more than 0.2% and wonderful (S,S)-isomers'percentage of not less than 75%.
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