title: Amycolamicin: a novel broad-spectrum antibiotic inhibiting bacterial topoisomerase.
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.
authors.affiliation: Institute of Microbial Chemistry, BIKAKEN, Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Hashizume
authors.forename: Kazushige
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ishizaki
authors.forename: Maya
authors.initials: M
authors.lastname: Umekita
authors.forename: Masaki
authors.initials: M
authors.lastname: Hatano
authors.forename: Hikaru
authors.initials: H
authors.lastname: Abe
authors.forename: Takumi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinoshita
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Homma
authors.forename: Chigusa
authors.initials: C
authors.lastname: Hayashi
authors.forename: Kunio
authors.initials: K
authors.lastname: Inoue
authors.forename: Syunichi
authors.initials: S
authors.lastname: Ohba
authors.forename: Toru
authors.initials: T
authors.lastname: Masuda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Arakawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masa
authors.initials: M
authors.lastname: Hamada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Hayamitsu
authors.initials: H
authors.lastname: Adachi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Akamatsu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D005960:Glucosides; D011758:Pyrroles; D059005:Topoisomerase II Inhibitors; C548730:amycolamicin; D027101:DNA Topoisomerase IV