メタゲノム採掘により,ポリテオナミドが翻訳後に改変されたリボソームペプチドであることを明らかにした
Michael F Freeman1, Cristian Gurgui, Maximilian J Helf
1Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Science (New York, N.Y.)
|September 18, 2012
まとめ
この研究は,海洋スポンジの毒素が細菌によってリボソームで合成され,リボソーム産物におけるl-アミノ酸のみのパラダイムに挑戦することを明らかにしています. これらの毒素は,強力な単分子イオンチャネルとして機能します.
科学分野:
- バイオケミストリーと分子生物学
- 自然製品化学 自然製品化学
- マリン・バイオロジー マリン・バイオロジー
背景:
- 支配的なパラダイムは,リボソームで合成されたペプチドとタンパク質は,独占的にl-アミノ酸を含んでいると述べています.
- 海洋スポンジ由来ポリテオナミドは,複雑な構造を持つ強力な天然産物毒素である.
- このような複雑な天然製品の生合成経路は,しばしば解明することが困難である.
研究 の 目的:
- 海洋スポンジ由来ポリテオナミドの生物合成起源を調査する.
- これらの毒素の翻訳後の改変に責任を負う酵素を特定し,特徴づけること.
- イオンチャネルとしてのポリテオナミドの機能的メカニズムを理解する.
主な方法:
- 海洋スポンジメタゲノムから生合成遺伝子の分離.
- 翻訳後の改変に関与する候補酵素を特定するためのバイオ情報分析.
- ラジカルS-アデノシルメチオニン酵素を含む候補酵素の機能的検証.
主要な成果:
- ポリテオナミドの生物合成遺伝子は,バクテリアの遺伝子構造を示しています.
- 広範なエピメリゼーションとメチレーションを含む48の翻訳後の改変のために6つの候補酵素が特定されました.
- ラジカルなS-アデノシルメチオニン酵素が,複数のアミノ酸の一方的エピメリゼーションを触媒として有効化されました.
結論:
- ポリテオナミドはリボソームで合成され,リボソーム製品におけるl-アミノ酸の独占的な使用に異議を唱える.
- エピメリゼーションとメチル化を含む複雑な翻訳後の改変は,毒素の機能にとって極めて重要です.
- これらの発見は,リボソーム系の既知の生物合成能力を拡張し,ペプチドバイオエンジニアリングの機会を提供します.
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