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Through the integration of enzyme screening and structure\u2010guided protein engineering, a double mutant of HheC (T134S\/W139M) was created for the enantioselective halogenation of spiro\u2010epoxyoxindoles, delivering chiral \u03b2\u2010haloalcohols in high yields (up to 50%) and optical purity (up to 98%\n                    <jats:italic>ee<\/jats:italic>\n                    ). Meanwhile, a nonenantioselective double mutant of HheG (I104F\/N196G) was identified for the efficient halogenation of racemic or enantiopure spiro\u2010epoxyoxindoles, affording the corresponding \u03b2\u2010haloalcohols in up to 98% yield. The biohalogenation systems were performed using copper halides as the halogenating reagent under whole\u2010cell catalysis and exhibit satisfactory substrate generality. When cell\u2010free extract was used as the biocatalyst, several other halide salts were also proved effective for the biohalogenation reaction. Remarkably, seawater served as a natural halogenating agent, enabling gram\u2010scale synthesis of chiral \u03b2\u2010haloalcohols. Representative downstream transformations of chiral \u03b2\u2010haloalcohols further showcased the synthetic utility of the enantioselective biohalogenation platform. Together, these findings not only expand the catalytic repertoire of halohydrin dehalogenases but also provide a viable biohalogenation strategy for the synthesis of chiral \u03b2\u2010haloalcohols from readily available epoxides.\n                  <\/jats:p>","DOI":"10.1002\/anie.6230875","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:41:26Z","timestamp":1787632886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enantioselective Biohalogenation of Spiro\u2010Epoxyoxindoles Enabled by Engineered Halohydrin Dehalogenases"],"prefix":"10.1002","volume":"65","author":[{"given":"Hai\u2010Xia","family":"Zhang","sequence":"first","affiliation":[{"name":"Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of 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