{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:51:00Z","timestamp":1792047060417,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22508358"],"award-info":[{"award-number":["22508358"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Imine reductases (IREDs) represent a highly promising class of biocatalysts for the asymmetric synthesis of chiral amines bearing two stereogenic centers. Herein, we report an IRED\u2010catalyzed asymmetric reductive amination strategy that converts racemic ketones into \u03b3\u2010piperidinamines with contiguous stereocenters and operates through a pathway consistent with a dynamic kinetic resolution\u2010asymmetric reductive amination (DKR\u2010ARA). The wild\u2010type\n                    <jats:italic>Ac<\/jats:italic>\n                    IRED afforded the 1\u2010benzyl\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010cyclopropyl\u20103\u2010methylpiperidin\u20104\u2010amine (\n                    <jats:bold>1a<\/jats:bold>\n                    ) in 60.8% conversion, but with only 78.5% enantiomeric excess (\n                    <jats:italic>ee<\/jats:italic>\n                    <jats:sub>cis<\/jats:sub>\n                    ) for (3\n                    <jats:italic>S<\/jats:italic>\n                    ,4\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1a<\/jats:bold>\n                    and 23.5%\n                    <jats:italic>ee<\/jats:italic>\n                    <jats:sub>trans<\/jats:sub>\n                    for (3\n                    <jats:italic>R<\/jats:italic>\n                    ,4\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1a<\/jats:bold>\n                    , giving an 84:16 diastereomeric ratio (\n                    <jats:italic>dr<\/jats:italic>\n                    ). To enhance stereoselectivity, we employed a \u201ctrans\u2010drop, enantio\u2010catch\u201d strategy to reshape the pocket architecture of\n                    <jats:italic>Ac<\/jats:italic>\n                    IRED. The resulting variant Mut\u20105 afforded 99.9%\n                    <jats:italic>ee<\/jats:italic>\n                    <jats:sub>cis<\/jats:sub>\n                    for (3\n                    <jats:italic>S<\/jats:italic>\n                    ,4\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1a<\/jats:bold>\n                    and &gt;\u200999:1\n                    <jats:italic>dr<\/jats:italic>\n                    , along with a 19\u2010fold increase in specific activity and a 24.7\u00b0C elevation in . Remarkably, at a cumulative substrate loading of 700\u2009mM (142.3\u2009g\u00b7L\n                    <jats:sup>\u20131<\/jats:sup>\n                    ), Mut\u20105 furnished (3\n                    <jats:italic>S<\/jats:italic>\n                    ,4\n                    <jats:italic>R<\/jats:italic>\n                    )\n                    <jats:bold>\u22121a<\/jats:bold>\n                    with 95% conversion, a space\u2010time yield (STY) of 208.7\u2009g\u00b7L\n                    <jats:sup>\u20131<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u20131<\/jats:sup>\n                    . This strategy not only provided highly efficient imine reductases but also established a robust platform for the atom\u2010economical synthesis of \u03b3\u2010piperidinamine building blocks bearing two stereogenic centers.\n                  <\/jats:p>","DOI":"10.1002\/bit.70416","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:43:47Z","timestamp":1792046627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Highly Diastereo\u2010 and Enantioselective Imine Reductases Engineered for \u03b3\u2010Piperidinamines Bearing Contiguous Stereocenters"],"prefix":"10.1002","author":[{"given":"Min\u2010Min","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou China"},{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs Deqing China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment (Zhejiang University of Technology) of Ministry of Education Deqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Neng","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs Deqing China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment (Zhejiang University of Technology) of Ministry of Education Deqing China"},{"name":"College of Pharmaceutical Sciences, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs Deqing China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment (Zhejiang University of Technology) of Ministry of Education Deqing China"},{"name":"College of Pharmaceutical Sciences, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-7314","authenticated-orcid":false,"given":"Zhe","family":"Dou","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs Deqing China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment (Zhejiang University of Technology) of Ministry of Education Deqing China"},{"name":"College of Pharmaceutical Sciences, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-0882","authenticated-orcid":false,"given":"Ya\u2010Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs Deqing China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment (Zhejiang University of Technology) of Ministry of Education Deqing China"},{"name":"College of Pharmaceutical Sciences, Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2782"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.0c00029"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c11354"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.4c00783"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bbb\/zbaf181"},{"key":"e_1_2_10_9_1","unstructured":"Godfrey A. 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