人工シフ塩基形成酵素によって触媒化された速 Knoevenagel 凝縮
Xavier Garrabou1, Basile I M Wicky1, Donald Hilvert1
1Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
Journal of the American Chemical Society
|May 20, 2016
まとめ
エンジニアリングされた酵素は 新しい反応を起こすことができます 設計された酵素であるRA95.5-8は,ノイヴェナゲルの凝縮を効率的に触媒化するために最適化され,従来の化学的触媒に比べて有意な触媒的優位性を示した.
科学分野:
- 生物触媒と酵素工学
- 合成化学
- コンピュータ生物学
背景:
- 酵素は触媒性を持ち,自然基質を超えた反応を触媒化することができます.
- コンピュータによる設計と 導かれた進化は,望ましい機能を持つ新しい酵素を生み出すための強力なツールです.
研究 の 目的:
- 計算で設計されたレトロアルドラーゼRA95.5-8のKnoevenagel凝縮活動を調査する.
- RA95.5-8の誘導効率を誘導進化によってKnoevenagel凝縮を高めるため
主な方法:
- RA95.5-8の水性ポケット内の反応性ライシン残留物を利用してKnoevenagel凝縮を加速した.
- 酵素の活性と触媒の効率を最適化するために 誘導進化を用いた.
- 酵素の触媒性能を評価し,アミン触媒と比較した.
主要な成果:
- 人工レトロアルドラーゼRA95. 5-8は,Knoevenagelの散乱凝縮活性を示した.
- 誘導的な進化により, 5 × 10 ^ 11 M ^ 1 の触媒能力を持つ最適化された酵素の変種が得られました.
- 進化した酵素は,単純な一次性アミンと二次性アミンに比べて10^8倍以上の触媒優位性を示した.
結論:
- 計算で設計された酵素は 価値ある化学的乱交の源となる.
- 誘導進化は 合成的に有用な反応のために 生物触媒を調整する効果的な戦略です
- 新しい酵素の進化は新しい生物触媒を作るための有望な経路を提供します.
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