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Herein, engineered Lactobacillus kefir Alcohol Dehydrogenase (LkADH) whole-cell catalysts enable aqueous asymmetric reduction of cyclohexylidene ketones toward S-configured axially chiral alcohols. The L153K variant gave 94% conversion and 98:2 er for 2a; diverse aryl\/heteroaryl substrates afforded products with high conversions and up to 99:1 er. The whole-cell strategy avoids enzyme purification and the addition of a separate purified GDH cofactor-recycling enzyme, facilitating practical synthesis verified by scale-up and downstream derivatization. This work develops a biocatalytic route and broadens the synthetic scope of LkADH reduction for uncommon axially chiral alcohols.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c03265","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:01:36Z","timestamp":1788800496000},"page":"11613-11619","source":"Crossref","is-referenced-by-count":0,"title":["Whole-Cell LkADH-Catalyzed Asymmetric Reduction Enables\nDirect Access to Cyclohexylidene Axially Chiral Alcohols"],"prefix":"10.1021","volume":"28","author":[{"given":"Wanxu","family":"Gao","sequence":"first","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, P. R. China, 130023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjia","family":"Yu","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, P. R. China, 130023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, P. R. China, 130023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxi","family":"Li","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, P. R. China, 130023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-0613","authenticated-orcid":true,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, P. R. China, 130023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Hospital of Jilin University , ,","place":["Changchun, P. R. 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