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Here, we report an asymmetric enzymatic hydrophosphorylation through oxygen activation using a repurposed flavin-dependent enzyme. Mechanistic studies revealed that reactive oxygen species are converted into productive phosphorus-centered radicals, followed by radical addition and enzymatic hydrogen atom transfer, achieving high enantioselectivity. The enzyme accommodates diverse phosphorus-hydrogen donors that pose challenges to chemical catalysis, enabling the biosynthesis of valuable phosphorus-containing scaffolds. This work expands the scope of biocatalysis to programmable carbon-phosphorus bond formation and establishes a paradigm for channeling oxygen reactivity in enzymes.<\/jats:p>","DOI":"10.1126\/science.aef3001","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:00:31Z","timestamp":1791482431000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Asymmetric enzymatic hydrophosphorylation through O\n                    <sub>2<\/sub>\n                    activation"],"prefix":"10.1126","volume":"394","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-8818","authenticated-orcid":true,"given":"Yi","family":"Zhou","sequence":"first","affiliation":[{"name":"DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, IL, USA."},{"name":"Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA."},{"name":"Carl R. 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