異常なエポキシイソニトリルを含む抗生物質アエロシアニジンとアミコミシンの生物合成
Ziyang Zheng1, Jon Clardy2, Hung-Wen Liu1,3
1Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
Journal of the American Chemical Society
|July 23, 2024
まとめ
アエロシアニジンとアミコミシン抗生物質の生物合成が解明され,イソニトリル中間産物への保存経路と明確な酸化変化が明らかにされました. この研究は,彼らのユニークなエポキシイソニトリル分子の形成を明らかにします.
科学分野:
- 自然製品の生物合成
- 有機化学
- 酵素学
背景:
- アエロシアニジンとアミコミシンは,希少なエポキシイソニトリル基を備えた複合抗生物質です.
- 合成は困難で 生体合成の経路は ほとんど知られていません
- 特定された遺伝子クラスターには,観察された酸化変化に対する期待される酵素が欠けている.
研究 の 目的:
- エアロシアニジンとアミコミシンの 生合成経路を完全に解明する.
- 独特のエポキシイソニトリル分子の形成を理解するために
- 主要な酸化過程の酵素を特定する.
主な方法:
- 遺伝子クラスターのバイオ情報分析
- 経路のステップを確認するための酵素分析
- 中間製品と最終製品の特徴
主要な成果:
- 双機能チオエステラゼとα-ケトグルタレット依存酵素を含む,イソニトリル中間産物への保存経路が特定されました.
- イソニトリル中間物質は,アシルキャリアタンパク質 (ACP) に負荷され,ポリケチド合成によって拡張されます.
- アエロシアニジンの生物合成には,エポキシデーションのためのクピンタンパク質 AecF が含まれており,アミコミシンは3つのP450酵素 (AmcB,AmcC,AmcQ) をエポキシデーションおよびケト形成に使用しています.
結論:
- この研究は,エアロシアニジンとアミコミシンの生合成経路を完全に解明しています.
- 保存された経路は, γ-ヒドロキシエポキシイソニトリル機能群の形成を説明する.
- 2つの抗生物質の間の最終的な構造的変化を決定するのは 独特の酵素機構です
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