{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:40:34Z","timestamp":1792262434255,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U2106227"],"award-info":[{"award-number":["U2106227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82022066"],"award-info":[{"award-number":["82022066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,10,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>N\u2010oxides are ubiquitous functional groups in natural products, conferring critical biological properties such as enhanced solubility and modulated membrane permeability. However, the biosynthetic pathways for N\u2010oxide formation in complex prenylated indole alkaloids (PIAs), especially the penicimutamides, remain poorly understood. Here, we describe the discovery and biochemical characterization of new activities of FAD\u2010dependent monooxygenase (FMO) PldC, which sequentially catalyzes the indole 2,3\u2010epoxidation\u2010rearrangement of penicimutamide E, and the regioselective N13\u2010oxidation of penicimutamide D to produce penicimutamide D N\u2010oxide. Furthermore, conserved N\u2010oxide\u2010forming activity was confirmed as a new function with another two known FMOs of CtdE and PhqK involved in the biosynthesis of citrinadins and paraherquamides, respectively. These findings provide mechanistic insights into FMO function, revealing a remarkable catalytic plasticity whereby a single enzyme family drives dual oxidative pathways (C\u2010oxidation and N\u2010oxidation) to generate structurally diverse alkaloid metabolites. Collectively, our findings expand the catalytic landscape of FMOs, suggesting N\u2010oxide formation as a conserved functional trait across this enzyme family during fungal PIA biosynthesis. These results also shed new light on the evolutionary trajectories and catalytic design principles of FMOs in the assembly of complex natural products.<\/jats:p>","DOI":"10.1002\/anie.9391687","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:17:53Z","timestamp":1788949073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery and Characterization of Conserved N\u2010Oxide\u2010Forming Function of FAD\u2010Dependent Monooxygenases for Fungal Prenylated Indole Alkaloid Biosynthesis"],"prefix":"10.1002","volume":"65","author":[{"given":"Tiandong","family":"Hu","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Marine Biology, Shandong Province Key Laboratory of Marine Biodiversity and Bio\u2010resource Sustainable Utilization, Institute of Oceanology Chinese Academy of Sciences  Qingdao China"},{"name":"State Key Laboratory of Microbial Technology Shandong University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Marine Biology, Shandong Province Key Laboratory of Marine Biodiversity and Bio\u2010resource Sustainable Utilization, Institute of Oceanology Chinese Academy of Sciences  Qingdao China"},{"name":"University of Chinese Academy of Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-3071","authenticated-orcid":false,"given":"Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anran","family":"Fu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Marine Biology, Shandong 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University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zechao","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Marine Biology, Shandong Province Key Laboratory of Marine Biodiversity and Bio\u2010resource Sustainable Utilization, Institute of Oceanology Chinese Academy of Sciences  Qingdao China"},{"name":"University of Chinese Academy of Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-870X","authenticated-orcid":false,"given":"Shengying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Shandong University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9459-680X","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental 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