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Their biosynthetic pathway involves two crucial non\u2010heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3\u2010alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.<\/jats:p>","DOI":"10.1002\/anie.202401324","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T03:04:13Z","timestamp":1710817453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Non\u2010Heme Iron Enzymes Catalyze Heterobicyclic and Spirocyclic Isoquinolone Core Formation in Piperazine Alkaloid Biosynthesis"],"prefix":"10.1002","volume":"63","author":[{"given":"Mai\u2010Truc","family":"Pham","sequence":"first","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Department of Chemistry National Tsing Hua University  Hsinchu 300 Taiwan R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica  Taipei 115 Taiwan R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u2010Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica  Taipei 115 Taiwan R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Huang","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica  Taipei 115 Taiwan R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-314X","authenticated-orcid":false,"given":"Hsiao\u2010Ching","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 115 Taiwan R.O.C."},{"name":"Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica  Taipei 115 Taiwan R.O.C."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"e_1_2_3_1_1","unstructured":"\u00a0"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/13895575113139990073"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.07.026"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(07)70175-4"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(91)90184-N"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NP00070A"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.32.786"},{"key":"e_1_2_3_8_1","unstructured":"\u00a0"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4NP00073K"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr200398y"},{"key":"e_1_2_3_11_1","unstructured":"\u00a0"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c12352"},{"key":"e_1_2_3_13_2","unstructured":"H.\u2005T. 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