Waldiomycin, a novel WalK-histidine kinase inhibitor from Streptomyces sp MK844-mF10
Waldiomycin, a novel WalK-histidine kinase inhibitor from Streptomyces sp MK844-mF10
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DOI：
10.1038/ja.2013.33
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发表时间：
2013-08-01
影响因子：
3.3
通讯作者：
Nomoto, Akio
中科院分区：
文献类型：
--
作者：
Igarashi, Masayuki;Watanabe, Takafumi;Nomoto, Akio
WalK是一种组氨酸激酶，WalR是一种反应调节剂，它们组成了一个双组分信号转导系统，对于低GC革兰氏阳性菌的细胞壁代谢是必不可少的。WalK抑制剂可能对耐甲氧西林金黄色葡萄球菌显示出杀菌作用。我们通过筛选放线菌代谢产物发现了一种新的WalK抑制剂，命名为沃尔多霉素。瓦多霉素属于安卡环素抗生素家族，结构上与二氧霉素相关。Waldiomycin抑制S.金黄色葡萄球菌和枯草芽孢杆菌的IC（50）分别为8.8和10.2 μ M，对耐甲氧西林的S. aureus和B. B.枯草杆菌。
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 IC(50)s 8.8 and 10.2 mu M, respectively, and shows antibacterial activity with MICs ranging from 4 to 8 mu g ml(-1) against methicillin-resistant S. aureus and B. subtilis.