非ヘム二鉄酵素CmlIによる6電子アリル-N-酸化のためのメカニズム
Anna J Komor, Brent S Rivard, Ruixi Fan1
1Department of Chemistry, Carnegie Mellon University , Pittsburgh, Pennsylvania 15213, United States.
Journal of the American Chemical Society
|May 21, 2016
まとめ
クロラムフェニコル (CAM) 生合成は,CmlIによって触媒化された多段階の酸化を含みます. 提案された触媒循環は,CAM生成のための最終的な6電子酸化を達成するために,酵素が酸素と中間物質をどのように使用するかを説明する.
科学分野:
- 生物化学
- 酵素学
- 有機化学
背景:
- クロラムフェニコル (CAM) バイオシンセシスは,アリルアミン前駆体 (NH2-CAM) を6電子酸化してアリルニトログループに結成する.
- この反応は,O2との反応で過酸化中産物 (P) を形成する非ヘム二鉄酸化酸素酵素CmlIによって触媒化される.
研究 の 目的:
- CAM生物合成における6電子酸化のメカニズムを解明する.
- CmlIペロキソ中間物質 (P) の役割を決定し,他の潜在的な酸化物質または中間物質を特定する.
主な方法:
- マススペクトロメトリーは,異なる酸素同位体条件下での反応産物を分析するために使用された ((18) O2 と (16) O2).
- NH2-CAMとその中間物質のCmlI触媒による酸化を研究するために,単一のターンオーバー反応を行った.
主要な成果:
- 質量スペクトロメトリーは,CAMナイトロ群の両方の酸素原子がO2から発生することを確認しました.
- 特定の条件下でCAMに18Oと16Oの両方の存在は,過酸化中産物 (P) の再構成を示した.
- 中間物質であるNH (OH) -CAMは,CmlIの差異性クラスタの再構成に起因する還元剤として特定された.
結論:
- NH2-CAMがNH ((OH)) -CAMに酸化され,その後CmlIが再減少し,Pリフォームが可能になる触媒サイクルが提案されています.
- 改造されたPはNH ((OH)) -CAMをNO-CAMに酸化し,その後CAMに酸化し,第2のO2原子を組み込む.
- 完全な6電子酸化は活性部位内で発生し,外因的な電子が2つしか必要とされません.
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