Ir (Me) -PIXコファクターを含むサイトクロームP450によって触媒化された化学選択性C-H結合アミネーション
Paweł Dydio1,2, Hanna M Key1,2, Hiroki Hayashi1,2
1Department of Chemistry, University of California , Berkeley, California 94720, United States.
Journal of the American Chemical Society
|January 13, 2017
まとめ
イリジウム共因子で設計されたP450酵素は,C-H結合アミネーションで高収量と選択性を達成し,鉄ベースのシステムを上回ります. この画期的な発見により 複雑な分子の効率的な触媒合成が 可能になりました
科学分野:
- 生物触媒
- 有機金属化学
- 酵素工学
背景:
- サイトクロームP450酵素は,アビオロギー的なC-H結合アミネーションのために設計されています.
- 低化学選択性と基質の範囲は,現在のP450触媒化アミネーション反応を制限する.
- アジド基質をスルフォナミドに還元する競争は大きな課題です.
研究 の 目的:
- 化学選択性を向上させ,C-Hアミネーションのためのより広い基板範囲を持つP450酵素を設計する.
- イリジウムポルフィリン共因子のP450触媒化アミネーションでの使用を調査する.
- 改良された酵素変種を特定するための効率的な方法を開発する.
主な方法:
- イリジウムポルフィリン共因子 (Ir ((Me) -PIX) による熱性生物からのP450を設計する.
- サルフォニルアジドのエナンチオセレクティブC-H結合アミネーションを触媒化する.
- 細胞溶解物におけるIr (Me) - PIXを含むCYP119変異体を迅速に検知する.
主要な成果:
- アジド還元よりもC-Hアミネーションの高い化学選択性 (> 20: 1) が得られた.
- 生産量は最大98%で,売上高 (トン数) は約300です.
- 95: 5までエナチオセレクティブ性が示され,部位選択性が異なっています.
- 鉄ポルフィリンを含む酵素と比較して,より広い基板範囲.
結論:
- 含有P450sのIr (Me) -PIXは,ヘムベースの酵素と比較して,C-Hアミネーションの優れた性能を提供します.
- 細胞溶解物における急速なスクリーニングは,高度に活性な酵素変異体の発見を加速します.
- この研究は,C-Hアミネーション反応に挑戦する酵素を発見するためのプラットフォームを提供します.
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