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Here we demonstrate that Baker's yeast, a widely used whole\u2010cell biocatalyst, retains catalytic activity and high stereoselectivity under ball\u2010milling conditions. This enables a highly stereoselective whole\u2010cell mechano\u2010biocatalytic reduction of \u03b1\u2010keto esters and aryl\u2013alkyl ketones, affording chiral alcohols with enantiomeric excesses up to &gt;99% under solvent\u2010minimized conditions. Both lyophilized and fresh yeast operate effectively, delivering E\u2010factors substantially lower than those obtained under conventional aqueous conditions (&gt;1000 in solution vs. 104\u201376 under mechano\u2010biocatalytic conditions). The process is scalable, as demonstrated by translation to a twin\u2010screw extrusion protocol, and significantly reduces waste compared with traditional whole\u2010cell reductions. These results establish whole\u2010cell mechanochemical biocatalysis as a practical and sustainable platform for asymmetric synthesis.<\/jats:p>","DOI":"10.1002\/cssc.70736","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:18:07Z","timestamp":1779337087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechano\u2010Biocatalytic Stereoselective Reduction of Ketones With Baker's Yeast Under Solvent\u2010Minimized Conditions"],"prefix":"10.1002","volume":"19","author":[{"given":"Alessandro","family":"Coco","sequence":"first","affiliation":[{"name":"Department of Chemistry Manufacturing Futures Lab University College London  London UK"},{"name":"Department of Drug and Health Sciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxue","family":"He","sequence":"additional","affiliation":[{"name":"Department of Chemistry 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Since the ketone substrate1aand product alcohol (R)\u20102aexhibit different absorptivity at 254 nm HPLC analysis can underestimate the conversions. Therefore crude reaction mixtures were analysed by1H NMR to obtain more accurate values which were nevertheless consistent with the trends observed by HPLC."},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/B815174A"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CE00778J"},{"key":"e_1_2_8_72_1","first-page":"1","article-title":"Baker's Yeast Catalyzed Asymmetric Reduction of Prochiral Ketones in Different Reaction Mediums","volume":"6","author":"Wolfson A.","year":"2013","journal-title":"Organic Communications"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68435-2"}],"container-title":["ChemSusChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cssc.70736","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cssc.70736","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cssc.70736","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:49:42Z","timestamp":1779882582000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cssc.70736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":72,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,5,27]]}},"alternative-id":["10.1002\/cssc.70736"],"URL":"https:\/\/doi.org\/10.1002\/cssc.70736","archive":["Portico"],"relation":{},"ISSN":["1864-5631","1864-564X"],"issn-type":[{"value":"1864-5631","type":"print"},{"value":"1864-564X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"2026-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70736"}}