Amycolamicin: A Novel Broad‐Spectrum Antibiotic Inhibiting Bacterial Topoisomerase |
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| Authors: | Dr. Ryuichi Sawa Dr. Yoshiaki Takahashi Dr. Hideki Hashizume Dr. Kazushige Sasaki Dr. Yoshimasa Ishizaki Maya Umekita Dr. Masaki Hatano Hikaru Abe Dr. Takumi Watanabe Naoko Kinoshita Yoshiko Homma Chigusa Hayashi Kunio Inoue Syunichi Ohba Toru Masuda Dr. Masayuki Arakawa Dr. Yoshihiko Kobayashi Dr. Masa Hamada Dr. Masayuki Igarashi Dr. Hayamitsu Adachi Dr. Yoshio Nishimura Dr. Yuzuru Akamatsu |
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| Affiliation: | 1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3‐14‐23, Kamiosaki, Shinagawa‐ku, Tokyo 141‐0021 (Japan), Fax: (+81)?3‐3441‐7589;2. Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, 3‐34‐17, Ida, Nakahara‐ku, Kawasaki‐shi, Kanagawa 211‐0035 (Japan);3. Institute of Microbial Chemistry (BIKAKEN), Numazu, 18‐24, Miyamoto, Numazu‐shi, Shizuoka 410‐0301 (Japan) |
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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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| Keywords: | antibiotics DNA replication natural products structure elucidation |
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