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普瑞巴林是治疗神经病理性疼痛、部分癫痫发作和焦虑症的重要药物。本文以外消旋异丁基丁二腈(IBSN)为底物,筛选获得了能够立体选择性合成普瑞巴林手性中间体(S)-3-氰基-5-甲基己酸的拟南芥腈水解酶NiT。考察了该腈水解酶催化IBSN水解的最适催化温度、pH、不同IBSN浓度及金属离子对酶催化反应的影响。结果表明,该酶的最适催化温度为30℃,最适pH为8.0,最适底物浓度为250mmol/L。在此条件下反应6h,(S)-3-氰基-5-甲基己酸的产率和光学纯度分别达到43%和95%。
Pregabalin is an important drug for the treatment of neuropathic pain, partial seizures and anxiety disorders. In this paper, racemic isobutylbutylnadinitrile (IBSN) as substrate, selected to be able to stereoselective synthesis of pregabalin chiral intermediate (S) -3-cyano-5-methylhexanoic acid Presenilin hydrolase NiT. The optimal catalytic temperature, pH, concentration of IBSN and the effect of metal ions on the enzymatic catalysis of IBSN hydrolysis catalyzed by nitrilase were investigated. The results showed that the optimum temperature for the enzyme was 30 ℃, the optimum pH was 8.0, and the optimum substrate concentration was 250mmol / L. Under the conditions of reaction 6h, the yield and optical purity of (S) -3-cyano-5-methylhexanoic acid reached 43% and 95%, respectively.