ピロロイミノキノン生物合成中の予期せぬ変異
Josseline Ramos Figueroa1, Lingyang Zhu1, Wilfred A van der Donk1
1Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|May 8, 2024
まとめ
ピロロイミノキノンの生物合成は,これまで考えられていたよりも複雑です. この研究では,アミノ群がglycine,asparagine,およびleucineからtRNA依存の経路で組み込まれ,以前の提案された経路に挑戦しています.
科学分野:
- 自然製品の生物合成
- 酵素学
- 分子 進化
背景:
- ピロロイミノキノンはトリプトファンから派生した生物学的活性のある天然製品です.
- 生物合成の経路は ほとんど知られていません
- 以前の研究では,トリプトファンの結合によってアンモサミド合成を開始するPEptide Aminoacyl- tRNA Ligase (PEARL) が確認された.
研究 の 目的:
- ピロロイミノキノンの複雑な生物合成経路を解明する.
- これらの化合物に組み込まれたアミノ群の源を特定する.
- 経路における重要な酵素の 進化的起源を調査する
主な方法:
- 2つの遺伝子クラスターから4つの追加の酵素の分析.
- tRNA依存のアミノ群の組み込みを調査する.
- FAD依存のグリシン酸化酵素 (Amm14) とキノン還元酵素の生化学的特徴.
主要な成果:
- 以前提案されたアンモサミドの生合成経路は誤っていることが判明しました.
- ピロロイミノキノンのアミノ群は,tRNA依存メカニズムで組み込まれたグリシン,アスパラジン,およびルシンの由来である.
- Amm14とキノン還元酵素は,それぞれグリシン,ルシン,アスパラジンから窒素を組み込むのに不可欠です.
結論:
- ピロロイミノキノンへの自然経路は 予想以上に複雑です
- 複数のアミノ酸源とtRNA依存メカニズムがそれらの生物合成に関与しています.
- PEARL と関連する酵素は,おそらく ATP-GRASP タンパク質ファミリーから進化した.
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