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Herein, we report a stereodivergent, one\u2010pot dual\u2010enzyme cascade that successfully overcomes these limitations to access all four stereoisomers of 2\u2010aminocyclohexanol from 1,2\u2010cyclohexanedione. Central to this strategy is the development of a \u201crudder\u201d model\u2010guided protein engineering approach, which reshaped the active site of\n                    <jats:italic>Lactobacillus kefiri<\/jats:italic>\n                    alcohol dehydrogenase (\n                    <jats:italic>Lk<\/jats:italic>\n                    ADH). This rational design yielded two key mutants, A145Q\/G195L and I144Y\/G195N, which exhibit exquisite stereocomplementary control over the critical monoreduction step. When coupled with stereoselective amine transaminases, this cascade operates with exceptional efficiency, delivering the target amino alcohols with yields up to 99% and excellent optical purity (&gt;\u200999%\n                    <jats:italic>ee<\/jats:italic>\n                    and up to 99%\n                    <jats:italic>de<\/jats:italic>\n                    ). This methodology not only provides a robust platform for the high\u2010atom\u2010economy synthesis of high\u2010value chiral building blocks but also demonstrates the power of structure\u2010based enzyme redesign in solving complex synthetic problems.\n                  <\/jats:p>","DOI":"10.1002\/bit.70183","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:56:51Z","timestamp":1773035811000},"page":"1380-1392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Guided Engineering of Alcohol Dehydrogenase for the Stereodivergent Synthesis of Amino Alcohols via Desymmetrization of Cyclic Diketones"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6122-4461","authenticated-orcid":false,"given":"Cheng\u2010Long","family":"Xu","sequence":"first","affiliation":[{"name":"College of Biotechnology and Bioengineering Zhejiang University of 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