RRC ID 35436
Author Sawa R, Takahashi Y, Hashizume H, Sasaki K, Ishizaki Y, Umekita M, Hatano M, Abe H, Watanabe T, Kinoshita N, Homma Y, Hayashi C, Inoue K, Ohba S, Masuda T, Arakawa M, Kobayashi Y, Hamada M, Igarashi M, Adachi H, Nishimura Y, Akamatsu Y.
Title Amycolamicin: a novel broad-spectrum antibiotic inhibiting bacterial topoisomerase.
Journal Chemistry
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.
Volume 18(49)
Pages 15772-81
Published 2012-12-3
DOI 10.1002/chem.201202645
PMID 23129443
MeSH Anti-Bacterial Agents / chemistry* Anti-Bacterial Agents / pharmacology* Bacteria / drug effects DNA Topoisomerase IV / antagonists & inhibitors* DNA Topoisomerase IV / chemistry* Glucosides / chemistry* Glucosides / pharmacology* Magnetic Resonance Spectroscopy Microbial Sensitivity Tests Pyrroles / chemistry* Pyrroles / pharmacology* Topoisomerase II Inhibitors*
IF 4.857
Times Cited 19
Prokaryotes E. coli ME8846(CAG12184)