Amycolamicin: A Novel Broad-Spectrum Antibiotic Inhibiting Bacterial Topoisomerase

作者：Sawa Ryuichi; Takahashi Yoshiaki; Hashizume Hideki; Sasaki Kazushige; Ishizaki Yoshimasa; Umekita Maya; Hatano Masaki; Abe Hikaru; Watanabe Takumi; Kinoshita Naoko; Homma Yoshiko; Hayashi Chigusa; Inoue Kunio; Ohba Syunichi; Masuda Toru; Arakawa Masayuki; Kobayashi Yoshihiko; Hamada Masa; Igarashi Masayuki; Adachi Hayamitsu^*; Nishimura Yoshio; Akamatsu Yuzuru

来源：Chemistry - A European Journal, 2012, 18(49): 15772-15781.

DOI：10.1002/chem.201202645

• antibiotics
• DNA replication
• natural products
• structure elucidation

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.

• 出版日期2012-12