分岐アルコキシ群のバイオシンセシス:コバラミン依存のラジカルSAM酵素によるイテラティブメチル群アルキレーション

Yuanyou Wang¹, Bastien Schnell², Sascha Baumann²

¹Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.

Journal of the American Chemical Society

|January 3, 2017

まとめ

研究者らは新しい酵素CysSを再構成し,単純なメチル基からt-ブチル基を含む複雑な分岐アルコキシ基を形成する能力を示した. この発見により,天然産物の生物合成と抗菌剤の開発の理解が進んでいます.

科学分野:

生物化学
自然製品の生物合成
酵素学

背景:

枝分かれしたアルコキシ群は,天然製品のt-ブチル群のように,生物合成経路が十分に理解されていない.
サイストバクタミドは,サイストバクター種から作られた新しい抗菌剤で,SAMメチルトランスフェラーゼであるCysSによって形成される可能性があるイソプロピル群を含んでいる.

研究の目的:

CysSの触媒活性を in vitroで調査する.
分岐アルコキシ群の形成,特にt-ブチル群のメカニズムを解明する.

主な方法:

p-アミノベンゾ酸チオエステル基板を使用してCysS触媒反応を再構成する.
酵素の基質特異性と産物形成を決定する生化学的測定法.

主要な成果:

CysSは,メチル基をエチル基とイソプロピル基に変換して,連続メチル化を触媒化する.
驚くべきことに,CysSはメチルグループの前駆体からセックブチルおよびtブチル群も生成する.
これは,t-ブチル群を形成するコバラミン依存の SAM 酵素の最初の in vitro 実証である.

結論:

CysSは,多様な枝分かれアルコキシ群を合成できる多用途酵素です.
この研究は,複雑な天然製品モチーフの生物合成に関する機械的洞察を提供します.
発見はSAM酵素の活動を理解し,設計するための新しい道を開きます.

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