バイオカタリティック・ステレオセレクティブ・オキシデーション (2-アリリンドール)
Sarah E Champagne1,2, Chang-Hwa Chiang1,2, Philipp M Gemmel1
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of the American Chemical Society
|January 18, 2024
まとめ
研究者は,フラビン依存モノオキシゲナーゼ (FDMOs) を使用した非対称な生物触媒酸化方法を開発し,3-ヒドロキシインドレーニンを合成した. 新しい酵素であるシャンペーズは ステレオ選択的にこれらの価値ある化合物を 高いエナティオメール過剰で生成しました
科学分野:
- 生物触媒
- 有機化学
- 酵素学
背景:
- 3-ヒドロキシインドレーニンは,天然製品や医薬品における重要な構造モチーフです.
- 3-ヒドロキシインドレニンの伝統的な化学合成は,過酸化や複雑な製品混合などの課題に直面しています.
- 酵素反応は,合成の障害を克服し,エンアンチオ濃縮された製品を生成するために高い選択性を提供します.
研究 の 目的:
- 3-ヒドロキシインドレーニンの合成のための効率的な非対称生物触媒酸化方法を開発する.
- ステレオ選択的インドル酸化を行うことができる新しい酵素を特定し,特徴づけること.
- 価値ある化学基板へのアクセスにおいて,工学によるフラビン依存モノオキシゲナーゼ (FDMOs) の応用を探求する.
主な方法:
- 祖先の配列空間,配列類似ネットワーク,およびディープラーニングを使用して開発されたフラビン依存モノオキシゲネーゼ (FDMOs) のキュレーションされたライブラリ.
- FDMOライブラリをスクリーニングして,2-アリリンドール基板の非対称性酸化を調べる.
- 特定された酵素の基板範囲とステレオ選択性の特徴付け.
- 反応条件の効率化とエナティオメール比率 (er)
主要な成果:
- *Coccidioides immitis* の Champase と呼ばれる,これまで特徴づけられていないFDMOが特定されました.
- Champaseは,様々な置換された2 - アリリンドールから3 - ヒドロキシインドレーニンへの酸化において高いステレオ選択性を示した.
- 酵素は中等から優れた収量と 95: 5 erまでのエナチオメール比率を達成しました.
- この研究は,インドル基板の範囲にわたる酵素の乱交性を示した.
結論:
- エンジニアリングされたFDMOs,特にChampaseを使用した非対称な生物触媒酸化は,エナチオ濃縮3ヒドロキシインドレニンのための効果的な経路を提供します.
- シャンパースは,有価な医薬品のステレオ選択合成のための新しい生物触媒です.
- このアプローチは伝統的な化学合成の限界を克服し,よりグリーンで選択的な代替案を提供します.
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