利用固定化脂肪酶高效生物催化合成普瑞巴林手性中间体。
Efficient Biocatalytic Synthesis of Chiral Intermediate of Pregabalin Using Immobilized Lipase.
机构信息
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, China.
出版信息
Biomed Res Int. 2018 Nov 1;2018:6192059. doi: 10.1155/2018/6192059. eCollection 2018.
A mutant L206F/P207F/L259F of lipase (TTL) exhibited high hydrolytic activity towards 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) for synthesis of ()-2-carboxyethyl-3-cyano-5-methylhexanoic acid (-CCMA), a key chiral intermediate of pregabalin. However, low conversion at high CNDE concentration and unreusability of the free TTL mutant restricted its industrial applications. In this study, the TTL mutant was immobilized onto epoxy resin and its catalytic properties for kinetic resolution of CNDE were investigated. Under the optimized conditions, the immobilized lipase exhibited an increased catalytic efficiency even at a CNDE concentration of 3 M with 49.7% conversion and 95% . The conversion retained higher than 46.3% even after 10 times repeated use of the immobilized lipase in -heptane-water biphasic system. These results demonstrated great potential of the immobilized TTL mutant for industrial production of the chiral intermediate of pregabalin.
脂肪酶（TTL）的突变体 L206F/P207F/L259F 对 2-羧乙基-3-氰基-5-甲基己酸乙酯（CNDE）具有很高的水解活性，可用于合成（）-2-羧乙基-3-氰基-5-甲基己酸（-CCMA），这是普瑞巴林的关键手性中间体。然而，高浓度 CNDE 时转化率低和游离 TTL 突变体的不可重复使用限制了其工业应用。在本研究中，将 TTL 突变体固定在环氧树脂上，并研究了其对 CNDE 的动力学拆分的催化性能。在优化条件下，即使在 CNDE 浓度为 3 M 的情况下，固定化脂肪酶的催化效率也有所提高，转化率为 49.7%，ee 值为 95%。即使在 -庚烷-水两相体系中重复使用 10 次后，固定化脂肪酶的转化率仍保持在 46.3%以上。这些结果表明，固定化 TTL 突变体在普瑞巴林手性中间体的工业生产中具有很大的潜力。
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