{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:12:37Z","timestamp":1761765157170,"version":"build-2065373602"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T00:00:00Z","timestamp":1243296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2009,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Ancillary oxygenase<\/jats:bold>: OxyE is identified as a likely ancillary C\u20104 hydroxylase used during oxytetracycline biosynthesis in <jats:italic>Streptomyces rimosus.<\/jats:italic> The synergistic actions of oxygenases OxyE and OxyL ensure complete oxidative tailoring and prevent irreversible shunt modifications of the biosynthetic intermediate.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/gif\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/mcontent.gif\"><jats:alt-text>magnified image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p><jats:italic>The double hydroxylation of 6\u2010pretetramid to 4\u2010keto\u2010anhydrotetracycline is a key tailoring reaction during the biosynthesis of the broad\u2010spectrum antibiotic tetracyclines. It has been shown previously by heterologous reconstitution that OxyL is a dioxygenase and is the only enzyme required to catalyze the insertion of oxygen atoms at the C\u201012a and C\u20104 positions. We report here that OxyE, a flavin adenine dinucleotide (FAD)\u2010dependent hydroxylase homologue, is an ancillary mono\u2010oxygenase for OxyL during oxytetracycline biosynthesis in<\/jats:italic> Streptomyces rimosus<jats:italic>. By using both gene disruption and heterologous reconstitution approaches, we demonstrated that OxyE plays a nonessential, but important role in oxytetracycline biosynthesis by serving as a more efficient C\u20104 hydroxylase. In addition, we demonstrated that partially oxidized biosynthetic intermediates can undergo various glycosylation modifications in<\/jats:italic> S. rimosus<jats:italic>. Our results indicate that the synergistic actions of OxyE and OxyL in the double hydroxylation step prevent accumulation of shunt products during oxytetracycline biosynthesis in<\/jats:italic> S. rimosus<jats:italic>.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cbic.200900122","type":"journal-article","created":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T14:32:13Z","timestamp":1243348333000},"page":"1544-1550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identification of OxyE as an Ancillary Oxygenase during Tetracycline Biosynthesis"],"prefix":"10.1002","volume":"10","author":[{"given":"Peng","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jixun","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,6,9]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/29.3.245"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00216-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.8.1829"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja800951e"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109755"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/a900566h"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90144-9"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"32829","DOI":"10.1016\/S0021-9258(17)46583-5","volume":"274","author":"Thamchaipenet A.","year":"1999","journal-title":"J. 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