Amycolamicin: A Novel Broad-Spectrum Antibiotic Inhibiting Bacterial Topoisomerase.

Chemistry. 2012 Nov 5. doi: 10.1002/chem.201202645. [Epub ahead of print]

Amycolamicin: A Novel Broad-Spectrum Antibiotic Inhibiting Bacterial Topoisomerase.

Sawa RTakahashi YHashizume HSasaki KIshizaki YUmekita MHatano MAbe HWatanabe TKinoshita NHomma YHayashi CInoue KOhba S,Masuda TArakawa MKobayashi YHamada MIgarashi MAdachi HNishimura YAkamatsu Y.

Source

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

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.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:

 23129443

[PubMed – as supplied by publisher]

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