Study On The Production Technology Of D-p-Hydroxyphenylglycine By The Method Of Combination Of Chemistry Synthesis And Enzyme

D-p-hydroxyphenylglycine (D-p-HPG) is one kind of important intermediate for the preparation of semisynthetic antibiotics, such as semisynthetic amoxicillin,ceforperazone and cefoprozil. In China, the satisfaction of need on D-p-HPG depends on importation. So it is necessary to study the production processes of D-p-HPG to find a new production method that is economical and high-efficient.The choice and breeding of fungus is key factor in production of D-p-HPG by enzyme method. In this paper, the Pseudomonas striata L2388 which can produce D-hydantoinase(D-Hase) and D-N-carbamylase(D-Case) was chosen . These two kinds of enzyme can directly transform D-p-hydroxyphenylhydantoin (D-p-HPH) to D-p-HPG. By experiments, the fermentation conditions of fungus were optimized and the optimal temperature and pH were determined. The enzymatic reaction conditions were also optimized by experiments and the optimal reaction temperature and pH were also determined. Through optimization, the yield rate of enzymatic reaction can reach to 99% that is no lower than the Japan production technology. The mechanism of enzymatic reaction was found by analyzing the transformation processes.The abstraction processes of D-p-HPG were studied. By combination of enzyme catalysis and chemistry synthesis method, the separation of product from mother liquor was successfully achieved. In order to get product with high quality, the second-time resin and mixed-beds exchange techniques were used, and the traditional 1×7 resin were given up. Trough this method, the quality of product is better than product imported in some ways.The new technology was successfully industrialization in Shijiazhuang Zhongtian Chemical Industry Co Ltd. Trough test in industrial manufacture, it was found that the quality of product is as good as those imported or better. The production cost of the new method is lower than simple chemistry synthesis method and enzyme catalysis method. The yield rate of this method(calculated from D-p-HPH) can reach to 89% which is higher than 86% reported in literatures. From August 2000 to March 2002, the new-increased tax and profit is 3297,0000 RMBs and the value of exported product reach to 584,0000$s. ...