リボソームを標的とする二機能性窒素結合二次代謝物質
Emilianne M Limbrick1, Michael Graf2, Dagmara K Derewacz1
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
Journal of the American Chemical Society
|July 26, 2020
まとめ
研究者らはマイクロモノスポラ・カルボナセアから 新種の抗生物質エヴェルニノミシンNとOを発見しました これらの化合物はエヴェルニノミシンとロサミシンの結合物であり,複数のリボソーム結合部位を標的として抗生物質耐性を抑制する可能性がある.
科学分野:
- 微生物学
- 自然製品化学
- 分子生物学
背景:
- 微生物は複数の抗生物質を 生成できるが,結合した作用は稀である.
- エヴァルニノミシンの産物であるMicromonospora carbonaceaには未発見の生物活性代謝物質が含まれている.
- 抗生物質耐性は 新しい治療戦略を必要とします
研究 の 目的:
- マイクロモノスポラ・カーボナセアの酸化酵素をコードする遺伝子を調査する.
- 生物によって生成される新しい抗生物質化合物を特徴付ける.
- これらの新しい結合体の作用機構と可能性を探求する.
主な方法:
- 酸化酵素をコードする遺伝子の遺伝的機能分析
- 新種の抗生物質 (エヴァルニノミシンN,O,P) の分離と構造の解明
- リボソーム結合試験,リガンド移位と化学防護試験を含む.
- 耐性変異プロフィールの分析
主要な成果:
- エヴェルニノミシンNとOの発見,ニトロンの部分で結合したエヴェルニノミシンとロサミシン.
- 非酵素凝縮によって形成された前駆体としてエヴェルニノミシンPの識別.
- エヴァルニノミシンPはマクロリドとオルソソミシンの両方のリボソーム部位に結合する.
- オートゴーナル結合部位を狙って 抵抗性の変異を克服する
結論:
- オートゴーナルな抗生物質製薬剤を組み合わせる戦略の実証
- 抗生物質の有意な共性変異に対する耐性が示された.
- ダブルサイトターゲティングによる抗生物質耐性対策の新たなアプローチを提案した.
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