ABC Transporter Genes, kasKLM, Responsible for Self-resistance of a Kasugamycin Producer Strain

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We previously reported that a 7.6-kb DNA fragment from <i>Streptomyces kasugaensis</i> M338-M1, a kasugamycin (KSM) producer, included KSM acetyltransferase gene (<i>kac</i><sup>338</sup>) and some other genes possibly involved in KSM biosynthesis. As an extension of that study, a 10-kb <i>Sac</i>I-<i>Kpn</i>I DNA fragment, located 5-15-kb upstream of <i>kac</i><sup>338</sup>, was cloned and a 4.2-kb <i>Sac</i>I-<i>Eco</i>RI fragment therefrom was sequenced, revealing one incomplete (designated ORF J) and three complete open reading frames (designated <i>kasK</i>, <i>kasL</i> and <i>kasM</i>). The coding frames of <i>kasK</i>, <i>L</i> and <i>M</i> overlap one another with terminator/initiator ATGA sequence. RT-PCR analysis of a DNA region including <i>kasKLM</i> indicated the presence of one transcript that is long enough to span the three genes. The <i>kasK</i> gene potentially encodes an ATP-binding protein of the ATP-binding cassette (ABC) transporter superfamily. Homology search for the deduced KasK protein shows similarity to other ABC transporters involved in self-resistance of a mithramycin and possibly doxorubicin producer strain. The <i>kasL</i> and <i>kasM</i> genes encode different integral membrane proteins, both having six putative transmembrane helices. An expression plasmid for <i>kasKLM</i> (pTV-KLM) was constructed and these genes were expressed in <i>E. coli</i> JM109, which had been sensitive to KSM. The transformant acquired resistance to KSM, suggesting that KasK, L and M proteins as a set in <i>S. kasugaensis</i> M338-M1 pump out KSM to protect the producer from its toxic metabolite.

収録刊行物

  • Journal of antibiotics

    Journal of antibiotics 53(4), 373-384, 2000-04-25

    公益財団法人 日本感染症医薬品協会

参考文献:  33件中 1-33件 を表示

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各種コード

  • NII論文ID(NAID)
    10008466657
  • NII書誌ID(NCID)
    AA0069330X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00218820
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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