バシルス・アミロリケファシエンスのトロイの木馬ペプチド・カルボキシメチル・シチジン抗生物質
Marina Serebryakova1,2, Darya Tsibulskaya1, Olga Mokina1,3
1Institute of Gene Biology, Russian Academy of Science , 34/5 Vavilov str., 119334 Moscow, Russia.
Journal of the American Chemical Society
|December 10, 2016
まとめ
研究者らはバチルス・アミロリケファシエンスの 新型マイクロシンC型抗生物質を発見しました この新しい化合物はアスパルチル-tRNA合成酵素を標的とし,バクテリアの耐性を防ぐためにカルボキシメチル化が特徴です.
科学分野:
- 微生物学
- 生物化学
- 分子生物学
背景:
- マイクロシンCはトロイの木馬のペプチドアデニラート抗生物質です
- 細胞内処理後にアスパルチル- tRNA合成酵素を抑制する.
- ペプチド前駆体のアデニル化は,MccB THIF型NAD/FADアデニルトランスフェラーゼによって触媒化される.
研究 の 目的:
- バシルス・アミロリケファシエンスの新型マイクロシンC型化合物の特徴
- 合成に伴う酵素的変化を調査する.
- 生物学的活性と抵抗を克服する可能性を評価する.
主な方法:
- バチルス・アミロリケファシエンスを用いたインビトロおよび細胞検査
- MccBとMccSの活性を調べるための酵素測定法
- マイクロシン構造と機能の分析
主要な成果:
- バチルス・アミロリケファシエンス (Bacillus amyloliquefaciens MccB) は,前駆体ペプチドに末端サイチジン一酸化物を結合する.
- サイトシン分子は,MccBとMccSによって媒介されるカルボキシメチル化によってさらに変化する.
- これらの改変されたマイクロシンC型化合物はアスパルチル- tRNA合成酶に対して活性であり,一般的な耐性メカニズムに抵抗します.
結論:
- 末端のサイトシン改変を有する新種のマイクロシンC型抗生物質が特定されました.
- 細胞酸のカルボキシメチル化は,生物学的活動を強化し,耐性を防止する重要な変化です.
- これらの発見は,新しい抗生物質の開発のためのペプチド改変の既知のレパートリーを拡張します.
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