Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.

寻找更快更简单的方法来筛选蛋白质序列空间以识别用于不对称合成的新生物催化剂仍然是酶发现中的挑战和限速步骤。用于合成手性胺的生物催化策略越来越有吸引力，包括酶促不对称还原胺化，它为许多这些高价值化合物提供了有效途径。在这里，我们报告了超过 300 种新亚胺还原酶的发现，以及可用于筛选的大量（384 种酶）和序列多样化的亚胺还原酶组的生产。我们还报告了一种简便的高通量屏幕的开发，以询问他们的活动。通过这种方法，我们确定了能够接受结构要求苛刻的酮和胺的亚胺还原酶生物催化剂，通过动态动力学拆分过程获得N取代的 β-氨基酯衍生物，具有出色的收率和立体化学纯度。