Enantiodivergent C-H Oxyfunctionalization Reactionsのための計算により設計されたペロキシゲナーズのレパートリー
Patricia Gomez de Santos1,2, Ivan Mateljak2, Manh Dat Hoang1,3
1Department of Biocatalysis, Institute of Catalysis, ICP-CSIC, C/ Marie Curie 2, 28049 Madrid, Spain.
Journal of the American Chemical Society
|January 23, 2023
まとめ
科学者は,強化されたC-Hオキシ機能化のためのFuncLibアルゴリズムを使用して新しい真菌ペロキシゲナスを設計しました. これらの生物触媒は,バイオテクノロジーの応用において,安定性,活性,および前例のない抗分岐性を示しています.
科学分野:
- 生物触媒
- タンパク質工学
- 合成化学
背景:
- 現代の合成化学には 生物触媒が不可欠です
- 菌類のペロキシゲネーゼはC-Hオキシ機能化の可能性を秘めているが,最適化が必要である.
研究 の 目的:
- 活性,安定,およびenantiodivergentの真菌ペロキシゲナーゼの多様なライブラリを設計し,生成する.
- C−Hオキシ機能化反応の触媒効率と選択性を改善する.
主な方法:
- 系統遺伝学とロゼッタ計算を組み込んだFuncLibアルゴリズムの適用.
- 触媒核に4〜5の変異がある24のペロキシゲナーゼの設計.
- イーストの機能表現とモデル化合物との比較
主要な成果:
- いくつかの合成ペロキシゲナーゼは,様々な温度とpHレベルにおいて高い活性と安定性を示した.
- 変異した地域選択性 (アルキルから芳香性水酸化) を有する前例のないエナチダイバージェンスを観察した.
- 触媒の効率は10倍まで上昇し,総周回数は親酵素と比較して15倍向上しました.
結論:
- FuncLibアルゴリズムは,自然界に存在しない,高度に機能するエナチオセレクティブペロキシゲナーゼを成功裏に生成した.
- 機能的差異は有益なエピスタシスとヘムチャネルの再編成による.
- これらのエンジニアリングされた酵素は,多様なバイオテクノロジーの応用のための大きな可能性を秘めています.
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