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We report here the engineering of cytochrome P450<jats:sub>BM3<\/jats:sub> (CYP102A1) for the selective oxidation of VD<jats:sub>3<\/jats:sub> to 25\u2010hydroxyVD<jats:sub>3<\/jats:sub>. Long\u2010range effects of the substrate\u2010channel mutation Glu435Ile promoted binding of the VD<jats:sub>3<\/jats:sub> side chain close to the heme, enhancing VD<jats:sub>3<\/jats:sub> oxidation activity that reached 6.62\u2005g of 25\u2010hydroxyVD<jats:sub>3<\/jats:sub> isolated from a 1\u2010litre scale reaction (69.1\u2009% yield; space\u2010time\u2010yield 331\u2005mg\/L\/h).<\/jats:p>","DOI":"10.1002\/chem.202401487","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T11:09:44Z","timestamp":1720091384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Selective Oxidation of Vitamin D<sub>3<\/sub> Enhanced by Long\u2010Range Effects of a Substrate Channel Mutation in Cytochrome P450<sub>BM3<\/sub> (CYP102A1)"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5517-8555","authenticated-orcid":false,"given":"Wenyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Oxford Inorganic Chemistry Laboratory  South Parks Road Oxford OX1 3QR UK"},{"name":"Oxford Suzhou Centre for Advanced Research  Ruo Shui Road, Suzhou Industrial Park Jiangsu 215123 P.R. 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