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Although we have successfully elucidated the biosynthetic pathway of\n                    <jats:bold>1<\/jats:bold>\n                    , the mechanism underlying the formation of the characteristic imidazolidin\u20104\u2010one remains unclear. In this study, we demonstrate that the cytochrome P450 monooxygenase CyaI catalyzes an oxidation reaction through a zwitterionic intermediate and facilitates a subsequent unusual C\u2192N acetyl migration, which triggers a spontaneous intramolecular cyclization to forge the imidazolidin\u20104\u2010one ring during\n                    <jats:bold>1<\/jats:bold>\n                    biosynthesis. In addition, CyaI is identified as a bifunctional enzyme that also catalyzes\n                    <jats:italic>N<\/jats:italic>\n                    \u2010demethylation. High\u2010resolution crystallography and mutagenesis studies determine Thr245 as a crucial catalytic residue that modulates the balance between imidazolidine\u20104\u2010one synthesis and demethylation. This work not only expands the catalytic repertoire of P450 enzymes but also opens the way for the development of multifunctional biocatalysts in the synthesis of complex natural products.\n                  <\/jats:p>","DOI":"10.1002\/anie.7360177","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:12:03Z","timestamp":1787631123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cytochrome P450 Enzyme\u2010Catalyzed Acetyl Migration in Cyanogramide Biosynthesis"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-8898","authenticated-orcid":false,"given":"Yiguang","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, Laboratory of Tropical Marine Bio\u2010resources and Ecology, South China Sea Institute of Oceanology Chinese Academy of 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