Huisgenaseの活性を持つバイオ分子を発見: (3 + 2) サイクル添加剤のバイオカタリストとして設計された繰り返しタンパク質
Iván Rivilla1, Mikel Odriozola-Gimeno1, Antonio Aires2
1Department of Organic Chemistry I, Centro de Innovación en Química Avanzada (ORFEO-CINQA) , Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) and Donostia International Physics Center (DIPC) , P° Manuel Lardizabal 3 , E-20018 Donostia/San Sebastián , Spain.
Journal of the American Chemical Society
|December 13, 2019
まとめ
ハイスゲネーゼと呼ばれる人工タンパク質は 不自然な1,3-二極反応を触媒化し,新しいニトロプロリンエステルを作ります. これらのタンパク質は反応の結果を正確に制御し,生物触媒の新たな境界を示しています.
科学分野:
- 生物触媒とタンパク質工学
- 有機合成と反応機構
- コンピュータ化学
背景:
- 酵素は通常 特定の自然反応を触媒します
- 1,3-二極循環加減は基本的な有機反応である.
- タンパク質に新しい触媒作用を 設計することは大きな課題です
研究 の 目的:
- イミンと二極性分子間の1,3-二極反応を触媒する新しいタンパク質の設計と特徴付け.
- 合成タンパク質の触媒メカニズムと 立体化学制御を調査する
- 生物触媒を用いて非自然なニトロプロリンエステルの形成を調査する.
主な方法:
- タンパク質の設計と再現タンパク質の構築
- 反応のモニタリングと構造分析のための核磁気共振 (NMR) スペクトロスコーピー.
- サイト・ディレクテッド・ミュータジェネシスで 触媒の残留を検出する.
- 機械学的洞察のための量子力学/分子力学 (QM/MM) の計算.
主要な成果:
- 設計された重複タンパク質は溶液中の1,3二極サイクロアディション反応を成功裏に触媒化した.
- 酸性アミノ酸と塩基性アミノ酸の両方が主要な触媒成分として特定されました.
- タンパク質の柔軟性とライシンとグルタミン酸残留物の正確な配置は,ダイアステレオコントロールに影響を与えました.
- エンジニアリングされたタンパク質は異常なダイアステロエーマーサイクロードダクトを生み出し,ニトロプロリンエステルを形成した.
結論:
- 設計されたタンパク質は,1,3-二極サイクロアディションのような自然界にない反応を触媒として設計することができる.
- 触媒活性とステレオ選択性は,特定のアミノ酸残留物とタンパク質構造によって制御されます.
- この研究は,非自然な化合物を合成するための新しい生物触媒 ("Huisgenases") を確立しています.
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