Enzymatic Synthesis of Simvastatin

• Main Authors: Chuang , Shu-Ju, 莊淑如
• Other Authors: Shaw, Shy-Yu
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/19065351443355197051

碩士 === 國立成功大學 === 化學系 === 89 === Simvastatin is a high efficiency, low side effect HMG-CoA reductase inhibitor used in the treatment of high cholesterol. Unlike Lovastatin, simvastatin can not be synthesized by fermantation and it is synthesized by semi-synthesis method. It has been reported that simvastatin can be synthesized by enzymatic method, and a fungal enzyme was used to hydrolyze of Lovastatin sodium-salt to yield Triol acid salt. If this enzyme can be purified and transformed into Escherichia coli ,and it can potentially improve the production cost and purity of Simvastatin. We attempt to synthesize a novel substrate for screening enzyme. This novel substrate is p-NPMB（para-Nitrophenyl (2-methyl)-butyrate). The enzymatic activity against p-NPMB was tested on fungal pellet and supernatant at various temperature and pH. The enzymatic activity is monitored at UV absorbance 400 nm. The result has shown that the pellet has the best activity at 27-37℃、pH 8, and the supernatant has the best activity at 37℃、pH 8. The reaction time is approximately 5-10 minutes. This method has been proved to a rapid method to examine the lovastatin hydrolyzed enzyme activity from fungus.