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Chiral\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2011fluoroamines are favored structural motifs in pharmaceuticals and agrochemicals, and the precise stereochemical configurations of the C\u2500F and C\u2500N stereogenic centers directly influence bioactivity. Despite the high value of chiral\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2011fluoroamines, existing synthetic approaches lack the capacity to deliver all possible stereoisomers in a single operation. Here we report the stereodivergent engineering of an imine reductase (IRED) into a set of stereocomplementary variants that enable programmable access to all four stereoisomers of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010fluoroamines via dynamic kinetic reductive amination (DKRA) of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2011fluoro\u2011ketones with amines. Leveraging the focused rational iterative site\u2010specific mutagenesis (FRISM) strategy, we precisely reprogrammed the enzyme active site by optimizing steric, electronic, and hydrogen\u2010bonding interactions with the key fluorinated imine intermediate. By generating and screening less than 100 variants, this engineering strategy yielded four stereoselective IRED variants, each selectively catalyzing the formation of a single stereoisomer of chiral\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010fluoroamines with exceptional stereoselectivity (up to &gt;20:1\n                    <jats:italic>dr<\/jats:italic>\n                    and 99%\n                    <jats:italic>ee<\/jats:italic>\n                    ) across a broad substrate scope. Kinetic studies and molecular dynamics simulations further elucidated the source of divergent stereoselectivity. This work accelerates the development of stereodivergent enzyme families for complex chiral synthesis.\n                  <\/jats:p>","DOI":"10.1002\/anie.1344095","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:57:31Z","timestamp":1788512251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accessing all Four Stereoisomers of\n                    <i>\u03b2<\/i>\n                    \u2010Fluoroamines by Engineered Imine Reductase\u2010Mediated Dynamic Kinetic Reductive Amination"],"prefix":"10.1002","volume":"65","author":[{"given":"Kongchen","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Chemistry Zhejiang University  Hangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Hangzhou P.R. 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