自然産物生物合成におけるSAM依存の酵素触媒による環状反応
Masao Ohashi1,2, Fang Liu3, Yang Hai1
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Nature
|September 14, 2017
まとめ
新しく発見されたLepI酵素は,S-アデノシル-l-メチオニン (SAM) を使用して複雑な回転反応を触媒化する. この酵素は自然産物のステレオ選択的合成を促進し,生物合成における新しい酵素経路を明らかにします.
科学分野:
- 生物化学
- 有機化学
- 自然製品合成
背景:
- 環循環反応は,高い選択性を持つ炭素-炭素結合を生み出すための強力なツールです.
- 周回反応の酵素触媒は稀で,以前は3つの例しか知られていなかった.
- 複雑な自然産物には しばしば これらの反応を用いて作られた構造があります
研究 の 目的:
- 自然産物の生合成に関与する新しい酵素を特定し,特徴づけること.
- 酵素触媒による循環反応のメカニズムを解明する.
- S-アデノシル-l-メチオニン (SAM) の酵素触媒における役割を調査する.
主な方法:
- 精製されたLepI酵素を用いた酵素分析
- 触媒活性のインビトロ特性
- 反応経路をモデル化するための計算研究 (例えば,密度関数理論).
- 菌類の天然産物レポリン構造の分析
主要な成果:
- S- アデノシル- 1 - メチオニン (SAM) 依存酵素であるLepIが特定されました.
- LepIはステレオ選択的脱水を催し,その後3つの環状変換:分子内ディエルス-アルダー,ヘテロ-ディエルス-アルダー,およびレトロ-クライゼン再編成を行います.
- これらの反応は,真菌の天然産物レポリンのディヒドロピラン核を形成する.
- LepIはSAMをコファクターとして利用し,生物合成経路の分岐を調節する.
結論:
- LepIは,複数の複雑な回転反応を触媒にできる新しい酵素を表しています.
- この発見は,酵素の周回変換の既知のレパートリーを拡張します.
- SAMは酵素触媒に多岐にわたる役割を果たし,未知の他の経路にも潜在的に作用する.
- この研究は,レポリンとキノコの天然産物の生物合成に関する洞察を提供します.
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