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Amycolamicin: A Novel Broad-Spectrum Antibiotic Inhibiting Bacterial Topoisomerase

Authors

  • Dr. Ryuichi Sawa,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Yoshiaki Takahashi,

    1. Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, 3-34-17, Ida, Nakahara-ku, Kawasaki-shi, Kanagawa 211-0035 (Japan)
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  • Dr. Hideki Hashizume,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Kazushige Sasaki,

    1. Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, 3-34-17, Ida, Nakahara-ku, Kawasaki-shi, Kanagawa 211-0035 (Japan)
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  • Dr. Yoshimasa Ishizaki,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Maya Umekita,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Masaki Hatano,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Hikaru Abe,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Takumi Watanabe,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Naoko Kinoshita,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Yoshiko Homma,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Chigusa Hayashi,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Kunio Inoue,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Syunichi Ohba,

    1. Institute of Microbial Chemistry (BIKAKEN), Numazu, 18-24, Miyamoto, Numazu-shi, Shizuoka 410-0301 (Japan)
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  • Toru Masuda,

    1. Institute of Microbial Chemistry (BIKAKEN), Numazu, 18-24, Miyamoto, Numazu-shi, Shizuoka 410-0301 (Japan)
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  • Dr. Masayuki Arakawa,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Yoshihiko Kobayashi,

    1. Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, 3-34-17, Ida, Nakahara-ku, Kawasaki-shi, Kanagawa 211-0035 (Japan)
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  • Dr. Masa Hamada,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Masayuki Igarashi,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Hayamitsu Adachi,

    Corresponding author
    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
    • Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Yoshio Nishimura,

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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  • Dr. Yuzuru Akamatsu

    1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3441-7589
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Abstract

The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution of multidrug resistance in many pathogens. Our efforts to discover novel classes of antibiotics to combat these pathogens resulted in the discovery of amycolamicin (AMM). The absolute structure of AMM was determined by NMR spectroscopy, X-ray analysis, chemical degradation, and modification of its functional groups. AMM consists of trans-decalin, tetramic acid, two unusual sugars (amycolose and amykitanose), and dichloropyrrole carboxylic acid. The pyranose ring named as amykitanose undergoes anomerization in methanol. AMM is a potent and broad-spectrum antibiotic against Gram-positive pathogenic bacteria by inhibiting DNA gyrase and bacterial topoisomerase IV. The target of AMM has been proved to be the DNA gyrase B subunit and its binding mode to DNA gyrase is different from those of novobiocin and coumermycin, the known DNA gyrase inhibitors.

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