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The key transformation during its biosynthetic pathway is a yet enigmatic skeletal reorganization from a 6\/5\/6 tetrahydro\u2010\u03b2\u2010carboline ring system to the 6\/6\/5 pyrroloquinoline scaffold, which is characteristic of camptothecin\u2010related alkaloids. Here, we show that this scaffold transition can be efficiently catalyzed by flavin cofactors such as flavin mononucleotide in a photooxidative process. As part of this complex transformation, we verified the existence of a previously postulated macrocyclic ketolactam intermediate. Based on the mild conditions\u2014oxygen, light, and flavins\u2014we show that this conversion can also take place in leaves of\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    , a plant which does not normally produce camptothecin or related alkaloids. Our optimized biomimetic photochemical reaction conditions enable a short, mild, and efficient semi\u2010synthesis of the alkaloids (3\n                    <jats:italic>S<\/jats:italic>\n                    )\u2010pumiloside, (3\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010pumiloside, and vincosamide ketolactam, also known as turpiniside, without any protecting groups. Thus, our work improves our understanding of this key skeletal reorganization step forming the camptothecin scaffold in nature and provides streamlined photocatalytic access to camptothecin\u2010related alkaloids.\n                  <\/jats:p>","DOI":"10.1002\/anie.4569029","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:07:58Z","timestamp":1782961678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation of the Camptothecin Scaffold by a Flavin\u2010Catalyzed Photooxidative Skeletal Reorganization"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1686-7330","authenticated-orcid":false,"given":"Shenyu","family":"Liu","sequence":"first","affiliation":[{"name":"Centre of Biomolecular Drug Research Leibniz University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Centre of Biomolecular Drug Research Leibniz University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2923-0701","authenticated-orcid":false,"given":"Benedikt","family":"Seligmann","sequence":"additional","affiliation":[{"name":"Centre of Biomolecular Drug Research Leibniz University Hannover  Hannover Germany"},{"name":"Institute of Botany Leibniz University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Hung","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Chemistry Irving K. Barber Faculty of Science University of British Columbia  Kelowna British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-3664","authenticated-orcid":false,"given":"Tuan\u2010Anh Minh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Irving K. Barber Faculty of Science University of British Columbia  Kelowna British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu\u2010Thuy T.","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Irving K. Barber Faculty of Science University of British Columbia  Kelowna British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Franke","sequence":"additional","affiliation":[{"name":"Centre of Biomolecular Drug Research Leibniz University Hannover  Hannover Germany"},{"name":"Institute of Botany Leibniz University Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00506a037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/np010042g"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2020.461036"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(01)80563\u20103"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104020(01)88369\u20101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(97)00858\u20107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.16.00193"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915\u2010021\u201001051\u2010y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jipb.13594"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.3c00222"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107980"},{"key":"e_1_2_10_13_1","first-page":"1710","article-title":"Photochemical Degradation of the Strictosamide\u2020","volume":"35","author":"Wenjun L. 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