{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T16:20:13Z","timestamp":1694622013097},"reference-count":30,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2000,4,1]],"date-time":"2000-04-01T00:00:00Z","timestamp":954547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The secondary metabolite 6-demethylchlortetracycline (6-DCT), which is produced by\n            <jats:italic>Streptomyces aureofaciens<\/jats:italic>\n            , is used as a precursor of semisynthetic tetracyclines. Strains that produce 6-DCT also produce a melanin-like pigment (MP). The correlation between MP production and 6-DCT production was investigated by using\n            <jats:italic>S. aureofaciens<\/jats:italic>\n            NRRL 3203. Production of both MP and 6-DCT was repressed by phosphate or ammonium ions, suggesting that syntheses of these compounds are controlled by the same regulators. Ten chlortetracycline-producing recombinants were derived from 6-DCT-producing mutant NRRL 3203 by gene replacement. All of the recombinants produced chlortetracycline but not MP, indicating that MP production is the results of a defect in the 6-methylation step and suggesting that the polyketide nonaketideamide is a common intermediate leading to MP as well as 6-DCT. To further examine the possibility that MP might be synthesized via the 6-DCT-biosynthetic pathway, mutants defective in 6-DCT biosynthesis were derived from a 6-DCT producer. Some of these mutants were able to produce MP, while others, including mutants with mutations in the gene encoding anhydrotetracycline oxygenase, an enzyme catalyzing the penultimate step in the pathway, produced neither 6-DCT nor MP. Production of 6-DCT and production of MP were restored simultaneously by integrative transformation with the corresponding 6-DCT-biosynthetic genes, indicating that some of 6-DCT-biosynthetic enzymes are indispensable for MP production. These findings suggest that a defect in the 6-methylation step results in redirection of carbon flux from a certain intermediate in the 6-DCT-biosynthetic pathway to a shunt pathway and results in MP production.\n          <\/jats:p>","DOI":"10.1128\/aem.66.4.1400-1404.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:30Z","timestamp":1027763730000},"page":"1400-1404","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Mechanism of the Incidental Production of a Melanin-Like Pigment during 6-Demethylchlortetracycline Production in\n            <i>Streptomyces aureofaciens<\/i>"],"prefix":"10.1128","volume":"66","author":[{"given":"Tetsuo","family":"Nakano","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Miyake","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Ikeda","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Mizukami","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Katsumata","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01388144"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"B\u011bhal\nV.\nHunter\nI. S.\nTetracyclines\nGenetics and biochemistry of antibiotics production.\nVining\nL. C.\nStuttard\nC.\n1995\n359\n384\nButterworth-Heinemann\nNewton Mass","DOI":"10.1016\/B978-0-7506-9095-9.50022-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.30.945"},{"key":"e_1_3_2_5_2","first-page":"215","article-title":"Regulation of biosynthesis of secondary metabolites. IX. The biosynthetic activity of blocked mutants of Streptomyces aureofaciens.","volume":"14","author":"Blumauerov\u00e1 M.","year":"1969","unstructured":"Blumauerov\u00e1 M. Mracek M. Vandr\u00e1\u010dkov\u00e1 J. Podojil M. Ho\u0161\u0165\u00e1lek Z. Van\u011bk Z. Regulation of biosynthesis of secondary metabolites. IX. The biosynthetic activity of blocked mutants of Streptomyces aureofaciens. Folia Microbiol. 14 1969 215 225","journal-title":"Folia Microbiol."},{"key":"e_1_3_2_6_2","unstructured":"Bu\u2032lock\nJ. D.\nThe biosynthesis of natural products.\n1965\nMcGraw-Hill Publishing Co. 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M.\nSchrempf\nH.\nGenetic manipulation of Streptomyces: a laboratory mannual.\n1985\nThe John Innes Foundation\nNorwich England"},{"key":"e_1_3_2_15_2","unstructured":"Ho\u0161\u0165\u00e1lek\nZ.\nBlumauerov\u00e1\nM.\nVan\u011bk\nZ.\nTetracycline antibiotics\nEconomic microbiology.\nRose\nA. H.\n1979\n293\n354\nAcademic Press\nLondon United Kingdom"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.35.1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-139-10-2525"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(00)93594-5"},{"key":"e_1_3_2_19_2","first-page":"2451","article-title":"Streptomycetes and related genera","volume":"4","author":"Locci L.","year":"1989","unstructured":"Locci L. Streptomycetes and related genera Bergey's manual of systematic bacteriology Williams S. T. Sharpe M. E. Holt J. G. 4 1989 2451 2508 Williams & Wilkins London, United Kingdom","journal-title":"Bergey's manual of systematic bacteriology"},{"key":"e_1_3_2_20_2","unstructured":"Maniatis\nT.\nFritsch\nE. F.\nSambrook\nJ.\nMolecular cloning: a laboratory manual\n2nd ed.\n1989\nCold Spring Harbor Laboratory\nCold Spring Harbor N.Y"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","unstructured":"McCormick\nJ. R. D.\nBiosynthesis of the tetracyclines\nBiogenesis of antibiotic substances.\nVan\u011bk\nZ.\nHo\u0161\u0165\u00e1lek\nZ.\n1965\n73\n91\nThe Czechoslovak Academy of Science\nPraque Czechoslovakia","DOI":"10.1016\/B978-0-12-395524-1.50012-6"},{"key":"e_1_3_2_22_2","unstructured":"McCormick J. R. D. April 1971. 6-Demethylchlortetracyclines and method for preparing the same. U.S. patent 3 616 239."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01503a066"},{"key":"e_1_3_2_24_2","unstructured":"Omura\nS.\nTanaka\nY.\nBiochemistry regulation and genetics of macrolide production\nMacrolide antibiotics.\nOmura\nS.\n1984\n199\n229\nAcademic Press\nNew York N.Y"},{"key":"e_1_3_2_25_2","first-page":"329","article-title":"Biochemical and genetic characterization of Streptomyces rimosus mutants impaired in oxytetracycline biosynthesis.","volume":"124","author":"Rhodes P. M.","year":"1981","unstructured":"Rhodes P. M. Winskill N. Friend E. J. Warren M. Biochemical and genetic characterization of Streptomyces rimosus mutants impaired in oxytetracycline biosynthesis. J. Gen. Microbiol. 124 1981 329 338","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_2_26_2","unstructured":"Ryan M. J. J. A. Lotvin N. Strathy and S. E. Fantini. December 1996. Cloning of the biosynthetic pathway for chlortetracycline and tetracycline formation and cosmids useful therein. U.S. patent 5 589 385."},{"key":"e_1_3_2_27_2","unstructured":"Tomita K. July 1996. Japanese patent."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02884211"},{"key":"e_1_3_2_29_2","unstructured":"Virgilio A. and C. Hengeller. December 1962. Process for the manufacturer of 6-demethylchlortetracycline. U.S. patent 3 070 514."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01573a090"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(85)90120-9"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.66.4.1400-1404.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.66.4.1400-1404.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T09:39:16Z","timestamp":1645609156000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AEM.66.4.1400-1404.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,4]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,4]]}},"alternative-id":["10.1128\/AEM.66.4.1400-1404.2000"],"URL":"https:\/\/doi.org\/10.1128\/aem.66.4.1400-1404.2000","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,4]]},"assertion":[{"value":"1999-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-01-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}