{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:23:59Z","timestamp":1790882639239,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["GM035906"],"award-info":[{"award-number":["GM035906"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["F-1511"],"award-info":[{"award-number":["F-1511"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2016,3,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    C3\u2032\u2010deoxygenation of aminoglycosides results in their decreased susceptibility to phosphorylation thereby increasing their efficacy as antibiotics. However, the biosynthetic mechanism of C3\u2032\u2010deoxygenation is unknown. To address this issue, aprD4 and aprD3 genes from the apramycin gene cluster in Streptomyces tenebrarius were expressed in E.\u2005coli and the resulting gene products were characterized in\u2005vitro. AprD4 is shown to be a radical S\u2010adenosylmethionine (SAM) enzyme, catalyzing homolysis of SAM to 5\u2032\u2010deoxyadenosine (5\u2032\u2010dAdo) in the presence of paromamine. [4\u2032\u2010\n                    <jats:sup>2<\/jats:sup>\n                    H]\u2010Paromamine was prepared and used to show that its C4\u2032\u2010H is transferred to 5\u2032\u2010dAdo by AprD4, during which the substrate is dehydrated to a product consistent with 4\u2032\u2010oxolividamine. In contrast, paromamine is reduced to a deoxy product when incubated with AprD4\/AprD3\/NADPH. These results show that AprD4 is the first radical SAM diol\u2010dehydratase and, along with AprD3, is responsible for 3\u2032\u2010deoxygenation in aminoglycoside biosynthesis.\n                  <\/jats:p>","DOI":"10.1002\/anie.201510635","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T05:36:30Z","timestamp":1455600990000},"page":"3724-3728","source":"Crossref","is-referenced-by-count":38,"title":["C3\u2032\u2010Deoxygenation of Paromamine Catalyzed by a Radical\n                    <i>S<\/i>\n                    \u2010Adenosylmethionine Enzyme: Characterization of the Enzyme AprD4 and Its Reductase Partner AprD3"],"prefix":"10.1002","volume":"55","author":[{"given":"Hak Joong","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Medicinal Chemistry College of Pharmacy and Department of Chemistry University of Texas at Austin  Austin TX 78712 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"LeVieux","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry College of Pharmacy and Department of Chemistry University of Texas at Austin  Austin TX 78712 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Cheng","family":"Yeh","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry College of Pharmacy and Department of Chemistry University of Texas at Austin  Austin TX 78712 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8953-4794","authenticated-orcid":false,"given":"Hung\u2010wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry College of Pharmacy and Department of Chemistry University of Texas at Austin  Austin TX 78712 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0301088"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/327389a0"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb3005116"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00874a003"},{"key":"e_1_2_2_5_1","first-page":"314","volume":"7","author":"Stark W. 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