2. Academic Validation
  3. Waldiomycin, a novel WalK-histidine kinase inhibitor from Streptomyces sp. MK844-mF10

Waldiomycin, a novel WalK-histidine kinase inhibitor from Streptomyces sp. MK844-mF10

  • J Antibiot (Tokyo). 2013 Aug;66(8):459-64. doi: 10.1038/ja.2013.33.
Masayuki Igarashi 1,  Takafumi Watanabe,  Tomohiro Hashida,  Maya Umekita,  Masaki Hatano,  Yohei Yanagida,  Hirokazu Kino,  Tomoyuki Kimura,  Naoko Kinoshita,  Kunio Inoue,  Ryuichi Sawa,  Yoshio Nishimura,  Ryutaro Utsumi,  Akio Nomoto
Affiliations

Affiliation

  • 1 Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. igarashim@bikaken.or.jp
PMID: 23632918 DOI: 10.1038/ja.2013.33
Abstract

WalK, a histidine kinase, and WalR, a response regulator, make up a two-component signal transduction system that is indispensable for the cell-wall metabolism of low GC Gram-positive bacteria. WalK inhibitors are likely to show bactericidal effects against methicillin-resistant Staphylococcus aureus . We discovered a new WalK inhibitor, designated waldiomycin, by screening metabolites from actinomycetes. Waldiomycin belongs to the family of angucycline Antibiotics and is structurally related to dioxamycin. Waldiomycin inhibits WalK from S. aureus and Bacillus subtilis at IC50s 8.8 and 10.2 μM, respectively, and shows Antibacterial activity with MICs ranging from 4 to 8 μg ml(-1) against methicillin-resistant S. aureus and B. subtilis.

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