クリソフェンチンA-Hは,細菌細胞分裂タンパク質FtsZを阻害する抗菌ビスディアリルブテンマクロサイクルである
Alberto Plaza1, Jessica L Keffer, Giuseppe Bifulco
1Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0820, USA.
Journal of the American Chemical Society
|June 12, 2010
まとめ
海洋藻からクリソフェンチンA-H,新しいマクロサイクリック抗生物質が生成されました. クリソフェンチンAは,細菌の細胞分裂の重要な成分であるFtsZタンパク質をターゲットにすることで,耐性菌を強力に抑制します.
科学分野:
- 海洋自然産物 化学 化学
- 微生物学 微生物学とは
- 構造生物学 構造生物学とは
背景:
- 抗生物質耐性の増大する脅威は,新しい抗菌剤の発見を必要としています.
- 海洋生物,特に藻類は,潜在的生物活性を持つ構造的にユニークな天然製品の豊富な供給源です.
研究 の 目的:
- 海洋キリソフィット藻 (Chrysophaeum taylori) から新しい抗菌化合物を分離し,特徴づけること.
- これらの新しい化合物の構造と作用メカニズムの解明.
主な方法:
- 2D NMRと質量スペクトロメトリを用いた分離と構造解明.
- 臨床的に重要なグラム陽性細菌に対する抗生物質感受性試験.
- 酵素阻害アッセイ,伝送電子顕微鏡,飽和伝送差 (STD) NMR,およびFtsZ阻害を調査するための分子ドッキング.
主要な成果:
- 8つの新しいマクロサイクリックな天然産物であるクライソファエンチンA-Hを分離し,特徴づけました.
- クリソフェンチンAは,メチチリン耐性である黄金球菌 (Staphylococcus aureus) とバンコマイシン耐性であるエンテロコッカス・フェシウム (Enterococcus faecium) に対して強力な活性を示した.
- クリソフェンチンAは,GTPaseの活性と,細菌の細胞骨格タンパク質FtsZのプロトフィラメント形成を抑制し,GTP部位に競争的に結合することが判明しました.
結論:
- クリソファエンチンA-Hは,重要な抗菌能力を持つ海洋天然製品の新しい構造クラスを表しています.
- FtsZ阻害を含むクリソフェンチンAの作用機構は,耐性菌株に対する抗生物質を開発するための有望な新しい道を提供します.
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