Identification of Novel Bacterial Members of the Imine Reductase Enzyme Family that Perform Reductive Amination
Identification of Novel Bacterial Members of the Imine Reductase Enzyme Family that Perform Reductive Amination
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DOI：
10.1002/cctc.201701408
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发表时间：
2018-02-07
期刊：
影响因子：
4.5
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
France, Scott P.;Howard, Roger M.;Turner, Nicholas J.
羰基化合物的还原胺化反应是快速构建手性和非手性胺框架的最有效方法之一。亚胺还原酶（IRED）生物催化剂是通过nadph介导的亚胺还原来合成胺的多用途酶家族。还原氨基酶（RedAms）是ired的一个亚家族，最近被证明可以催化亚胺的形成和亚胺的还原。在此，多种新型酶库被表达并筛选为无细胞裂解物，因为它们具有促进还原胺化的能力，从而扩展了用于这种转化的已知生物催化剂组合，并确定了更多具有潜在工业应用价值的酶。检测了一系列酮类和胺类，并确定了能够接受苄胺、吡咯烷、氨和苯胺的酶。低至2.5的胺当量可提供高达100 - 99%的转化率，对于手性产品，高达100 - 98%的转化率可以实现。制备级反应以低胺当量（1.5或2.0）的甲胺、烯丙胺和吡咯烷进行，转化率高达99%，收率达到76%。
Reductive amination of carbonyl compounds constitutes one of the most efficient ways to rapidly construct chiral and achiral amine frameworks. Imine reductase (IRED) biocatalysts represent a versatile family of enzymes for amine synthesis through NADPH-mediated imine reduction. The reductive aminases (RedAms) are a subfamily of IREDs that were recently shown to catalyze imine formation as well as imine reduction. Herein, a diverse library of novel enzymes were expressed and screened as cell-free lysates for their ability to facilitate reductive amination to expand the known suite of biocatalysts for this transformation and to identify more enzymes with potential industrial applications. A range of ketones and amines were examined, and enzymes were identified that were capable of accepting benzylamine, pyrrolidine, ammonia, and aniline. Amine equivalents as low as 2.5 were employed to afford up to >99% conversion, and for chiral products, up to >98%ee could be achieved. Preparative-scale reactions were conducted with low amine equivalents (1.5 or 2.0) of methylamine, allylamine, and pyrrolidine, achieving up to >99% conversion and 76% yield.