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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Amplification of the entire kanamycin biosynthetic gene cluster during empirical strain improvement of Streptomyces kanamyceticus
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Amplification of the entire kanamycin biosynthetic gene cluster during empirical strain improvement of Streptomyces kanamyceticus

机译：卡纳链霉菌经验菌株改良过程中整个卡那霉素生物合成基因簇的扩增

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摘要

Streptomyces kanamyceticus 12-6 is a derivative of the wild-type strain developed for industrial kanamycin (Km) production. Southern analysis and DNA sequencing revealed amplification of a large genomic segment including the entire Km biosynthetic gene cluster in the chromosome of strain 12-6. At 145 kb, the amplifiable unit of DNA (AUD) is the largest AUD reported in Streptomyces. 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 > 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.
机译：卡那链霉菌12-6是为工业卡那霉素（Km）生产而开发的野生型菌株的衍生物。 Southern分析和DNA测序揭示了一个大的基因组片段的扩增，包括菌株12-6的染色体中的整个Km生物合成基因簇。 DNA（AUD）的可扩增单位为145 kb，是链霉菌中报道的最大AUD。在AUD中发现了属于簇状规则间隔的短回文重复序列家族的惊人重复DNA序列，并可能在其扩增中发挥作用。菌株12-6包含具有不同数量AUD的不同染色体的混合物，有时超过36个拷贝，并产生一个大于5.7 Mb的扩增区域。 Km产生的水平取决于Km生物合成基因簇的拷贝数，这表明由于选择增加Km抗性而在菌株改良期间发生了DNA扩增。包括整个抗生素生物合成基因簇在内的DNA片段的扩增可能是导致工业菌株抗生素生产增加的常见机制。

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