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However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo\u2010 and enantioselective biocatalytic approach for preparing a broad range of \u03b2\u2010branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution\u2010asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild\u2010type <jats:italic>Poc<\/jats:italic>IRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to &gt;99.9\u2009%\u2005<jats:italic>ee<\/jats:italic>, &gt;99\u2009:\u20091\u2005<jats:italic>dr<\/jats:italic>, and &gt;99\u2009% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74\u2009% yield, &gt;99.9\u2009%\u2005<jats:italic>ee<\/jats:italic>, and 98\u2009:\u20092\u2005<jats:italic>dr<\/jats:italic> at a challenging substrate loading of 110\u2005g\u2009L<jats:sup>\u22121<\/jats:sup>. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution\u2010asymmetric reductive amination reaction system.<\/jats:p>","DOI":"10.1002\/anie.202408686","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T03:29:20Z","timestamp":1723174160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["An Engineered Imine Reductase for Highly Diastereo\u2010 and Enantioselective Synthesis of \u03b2\u2010Branched Amines with Contiguous Stereocenters"],"prefix":"10.1002","volume":"63","author":[{"given":"Zhen\u2010Yu","family":"Zhu","sequence":"first","affiliation":[{"name":"Laboratory of Biocatalysis and Synthetic Biotechnology State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  130 Meilong Road 200237 Shanghai PR 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