Enzymatic Resolution of Methyl DL-β-Acetylthioisobutyrate

• Main Authors: Yu-Ren Chen, 陳裕仁
• Other Authors: Shyh-Yu Shaw
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/29650448082037864073

碩士 === 國立成功大學 === 化學系 === 87 === Although certain hydrolytic enzymes such as lipase, esterase, and protease have been used to stereoselectively hydrolyze racemic compounds, they have not been extensively used in pharmaceutical industry. One of the major reasons is that the availability, quantity, and stability of such enzymes do not meet the requirements of pharmaceutical industry. Recent advance in genetic engineering has allowed us to clone genes encoding for trace amount of enzymes from various microorganisms and to express them in large quantities and the advance in protein engineering have allow us to improve the stability and substrate specificity of enzymes. These advances should make enzymes more available and suitable for being used in pharmaceutical industry. In this paper, we reported a stereoselective esterase cloned from Pseudomonas putida, expressed in E.coli, and used for optical resolution of methyl DL-β-acetylthioisobutyrate ( MATI ) to get D-β-acetylthioisobutyric acid（DAT）. DAT is a precursor of an antihypertensive drug ---Captopril. The D form is about 100 times more active than the L form, therefore it is important to resolve DAT with high optical purify. The stereoselective esterase possesses high stability toward temperature and pH changes, and can be produced in large quantities which allows this enzyme to be used in pharmaceutical industry.