Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
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樱桃中的羟基腈裂解酶同工酶：鉴定、表征和合成应用
DOI：
10.1002/adsc.201601332
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发表时间：
2017
影响因子：
5.4
通讯作者：
Yu Hui-Lei
中科院分区：
文献类型：
--
作者：
Zheng Yu-Cong;Xu Jian-He;Wang Hui;Lin Guo-Qiang;Hong Ran;Yu Hui-Lei
源自 Badamu（李）的生物催化剂已用于催化 (R)-4-甲硫基扁桃腈（甲砜霉素和氟苯尼考的关键组成部分）的不对称合成。在这里，来自巴达木的四种羟基腈裂解酶（HNL）同工酶被克隆并在毕赤酵母中异源表达。全面探讨了这些同工酶的生化性质和催化性能，以评估它们在不对称合成中的效率和选择性。其中，PcHNL5在不对称氢氰化反应中具有出色的活性和对映选择性。在优化的温和双相反应条件下，17种前手性芳香醛被转化为有价值的手性氰醇，具有良好的收率（高达94％）和优异的光学纯度（高达>99.9％ee），这为多种手性氨基醇、降血糖药、血管紧张素转换酶（ACE）抑制剂和β-受体阻滞剂提供了方便的途径。因此，这项工作强调了在一组同工酶中发现最有效的生物催化剂以将非天然底物转化为增值产品的重要性。
Biocatalysts originating from Badamu (Prunus communis) have been applied to catalyze the asymmetric synthesis of (R)-4-methylsulfanylmandelonitrile, a key building block of thiamphenicol and florfenicol. Here, four hydroxynitrile lyase (HNL) isozymes from Badamu were cloned and heterologously expressed in Pichia pastoris. The biochemical properties and catalytic performances of these isozymes were comprehensively explored to evaluate their efficiency and selectivity in asymmetric synthesis. Among then, PcHNL5 was identified with outstanding activity and enantioselectivity in asymmetric hydrocyanation. Under the optimized mild biphasic reaction conditions, seventeen prochiral aromatic aldehydes were converted to valuable chiral cyanohydrins with good yields (up to 94%) and excellent optical purities (up to >99.9% ee), which provide a facile access to numerous chiral amino alcohols, hypoglycemic agents, angiotension converting enzyme (ACE) inhibitors and β-blockers. This work therefore underlines the importance of discovering the most potent biocatalyst among a group of isozymes for converting unnatural substrates into value-added products.