エナチオセレクティブ [2+2]サイクル添加剤のために設計された光酵素
Jonathan S Trimble1,2, Rebecca Crawshaw1,2, Florence J Hardy1,2
1Department of Chemistry, The University of Manchester, Manchester, UK.
Nature
|September 21, 2022
まとめ
研究者らは,トリプルエネルギー伝達 (EnT) 触媒の遺伝子コード拡張を用いた新しい光酵素を設計した. この突破は,穏やかな条件下で効率的でエナチオセレクティブ [2+2] サイクロアディションのための新しいタンパク質機能を可能にします.
科学分野:
- 生物触媒と合成化学
- タンパク質工学とバイオテクノロジー
背景:
- 遺伝子コードの拡張により,新しいタンパク質の機能のために非正規のアミノ酸を導入することができます.
- 三重エネルギー伝達 (EnT) 触媒は,現在バイオ触媒で利用できない強力な合成ツールです.
研究 の 目的:
- 三重エネルギー伝達 (EnT) 触媒を可能にする光酵素を開発する.
- タンパク質の構造を用いた 効率的でエナチオセレクティブな光触媒を設計する
主な方法:
- 遺伝コードの拡張を活用して,光敏感剤をデノボ・ディエルス・アルデラーゼ (DA_20_00) に導入した.
- 誘導的活性と選択性を高めるために光酵素を最適化するために,誘導的進化プラットフォームを使用した.
- 光酵素製品複合体のX線結晶構造を決定した.
主要な成果:
- EnT触媒による [2+2]サイクル添加のための光酵素 (EnT1.0) を生成した.
- 進化した変種 (EnT1.3) が開発され,99%のエナティオメール過剰 (e.e.) を達成した. 様々なサイクル添加物について
- >300回転,エアロビック安定性,環境温度での動作が実証され,小分子触媒の性能を上回る.
- 構造分析により,タンパク質の活性部位内での相乗効果が明らかになった.
結論:
- エンジニアリングされたタンパク質に基づく新世代のエナチオセレクティブ光触媒を作るための枠組みを確立した.
- タンパク質の活性部位における 興奮状態の化学反応の新たな可能性を 開いた.
- 合成変換に挑戦する光酵素の可能性を実証した.
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