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Striking repetitive DNA sequences belonging to the clustered regularly interspaced short palindromic repeats family were found in the AUD and may play a role in its amplification. Strain 12-6 contains a mixture of different chromosomes with varying numbers of AUDs, sometimes exceeding 36 copies and producing an amplified region &gt;5.7 Mb. The level of Km production depended on the copy number of the Km biosynthetic gene cluster, suggesting that DNA amplification occurred during strain improvement as a consequence of selection for increased Km resistance. Amplification of DNA segments including entire antibiotic biosynthetic gene clusters might be a common mechanism leading to increased antibiotic production in industrial strains.\n          <\/jats:p>","DOI":"10.1073\/pnas.0603251103","type":"journal-article","created":{"date-parts":[[2006,6,10]],"date-time":"2006-06-10T00:48:51Z","timestamp":1149900531000},"page":"9661-9666","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["Amplification of the entire kanamycin biosynthetic gene cluster during empirical strain improvement of\n            <i>Streptomyces kanamyceticus<\/i>"],"prefix":"10.1073","volume":"103","author":[{"given":"Koji","family":"Yanai","sequence":"first","affiliation":[{"name":"*Department of Molecular Microbiology, John Innes Centre, Colney, Norwich NR4 7UH, United Kingdom; and"},{"name":"Microbiological Resources and Technology Laboratories, Meiji Seika Kaisha Ltd., 788 Kayama, Odawara-shi, Kanagawa 2500852, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Microbiological Resources and Technology Laboratories, Meiji Seika Kaisha Ltd., 788 Kayama, Odawara-shi, Kanagawa 2500852, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mervyn","family":"Bibb","sequence":"additional","affiliation":[{"name":"*Department of Molecular Microbiology, John Innes Centre, Colney, Norwich NR4 7UH, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2006,6,20]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"181","volume":"10","author":"Umezawa H.","year":"1957","unstructured":"H. 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