{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:29Z","timestamp":1791331229466,"version":"4.3.1"},"reference-count":68,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2804300"],"award-info":[{"award-number":["2022YFC2804300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273826"],"award-info":[{"award-number":["82273826"]}],"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":["82574298"],"award-info":[{"award-number":["82574298"]}],"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":[[2026,7,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aziridine\u2010containing natural products are prized for their potent bioactivities, yet their scarcity and poorly understood biosynthesis have limited systematic exploration. Here, we address this by integrating genome mining with a\n                    <jats:sup>1<\/jats:sup>\n                    H\u2013\n                    <jats:sup>13<\/jats:sup>\n                    C coupled HSQC metabolomic approach that exploits the distinctive NMR signatures of aziridines, enabling their direct detection from complex extracts. This strategy unveiled the desertolides, the first macrolides incorporating a rare terminal 2\u2010methyl\u2010aziridine\u20102\u2010carboxylate moiety. Genetic and isotopic studies identified a dedicated biosynthetic subcluster (\n                    <jats:italic>desA<\/jats:italic>\n                    \u2013\n                    <jats:italic>desN<\/jats:italic>\n                    ) that assembles and installs this unit from glutamate, and heterologous expression confirmed the self\u2010sufficiency of this subcluster. Direct MS evidence reveals the aziridine moiety covalently bound to the active\u2010site Cys113 of DesN, establishing this KAS III homolog as the first dedicated aziridine\u2010transferase and a promising tool for polyketide engineering. Bioinformatic analysis uncovered over 50 biosynthetic gene clusters, suggesting that this aziridine\u2010associated biosynthetic logic may be more widespread than currently appreciated. This work establishes a tractable platform for the targeted discovery and engineered biosynthesis of aziridine\u2010containing natural products, opening this underexplored pharmacophore to systematic interrogation.\n                  <\/jats:p>","DOI":"10.1002\/anie.8862620","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:55:03Z","timestamp":1779699303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling Aziridine\u2010Containing Natural Products by Genomic and Spectroscopic Approaches"],"prefix":"10.1002","volume":"65","author":[{"given":"Ronghui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiting","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiudi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Research Center for Marine Drugs Renji Hospital School of Medicine, State Key Laboratory of Microbial Metabolism Shanghai Jiao Tong University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2709-4297","authenticated-orcid":false,"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences) Qilu University of Technology (Shandong Academy of Sciences)  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixin","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-1123","authenticated-orcid":false,"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongnan Hospital of Wuhan University TaiKang Center for Life and Medical Sciences School of Pharmaceutical Sciences Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-209650-1.50006-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1385272825666210728100022"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003717\u20107"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2023.04.010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202303069"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.8b01022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3OB00424D"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.05.013"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.11554\/antibioticsa.9.4_141"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.11554\/antibioticsa.9.4_147"},{"key":"e_1_2_8_12_1","first-page":"228","article-title":"Isolation of New Fractions of Antitumor Mitomycins","volume":"8","author":"Wakaki S.","year":"1958","journal-title":"Antibiotics and Chemotherapy"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001813\u2010199910000\u201000005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.589"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.594"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00247a043"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.607"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.600"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.39.1527"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.29.1001"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2181"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.46.1772"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.48.1148"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.48.217"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja001859j"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201004646"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja1101085"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202104644"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c08116"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c12664"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c07243"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja907307h"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201020018\u20108"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20102852(68)90030\u20101"},{"key":"e_1_2_8_35_1","first-page":"649","article-title":"Bonding in Functionalized Aziridines: Nitrogen\u201015 and Carbon\u201013 Studies","volume":"53","author":"Tarburton P.","year":"1980","journal-title":"Croatica Chemica Acta"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00957072"},{"key":"e_1_2_8_37_1","unstructured":"Deposition Numbers2453402(for6) and 2453403 (for7) Contain the Supplementary Crystallographic Data for this Paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378\u20101119(00)00171\u20102"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26310\u20100"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2003.12.010"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b00384"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.746"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.5c00835"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200800714"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.6b01043"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00551"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9MD00162J"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969\u20102126(00)00094\u20100"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010019\u20100400\u20109"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201001344\u20103"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010025\u201001878\u20104"},{"key":"e_1_2_8_52_1","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J.","year":"2001"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc10e03s19"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/md17120698"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf334"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0203s00"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.synbio.2019.02.004"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00985\u201013"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad359"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202007777"},{"key":"e_1_2_8_62_1","unstructured":"Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard\u2014ninth edition (M07\u2010A9). Clinical and Laboratory Standards Institute Wayne PA 2012 10\u201319."},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20101119(92)90627\u20102"},{"key":"e_1_2_8_64_1","first-page":"1","article-title":"Construction of Streptomyces Lividans SBT5 as an Efficient Heterologous Expression Host","volume":"33","author":"Bai T.","year":"2014","journal-title":"J Huazhong Agric Univ"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/417141a"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010017\u20108642\u20105"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u201097"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010008\u20101793\u20107"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200800008"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.8862620","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.8862620","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.8862620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:15:41Z","timestamp":1784542541000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.8862620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":68,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,7,20]]}},"alternative-id":["10.1002\/anie.8862620"],"URL":"https:\/\/doi.org\/10.1002\/anie.8862620","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"2025-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e8862620"}}