酵素によるβ-チオエーテル結合形成の根本的なアプローチ
Alessio Caruso1, Leah B Bushin1, Kenzie A Clark1
1Department of Chemistry , Princeton University , Princeton , New Jersey 08544 , United States.
Journal of the American Chemical Society
|December 7, 2018
まとめ
研究者達は新しい酵素NxxcBを発見し ベータ-チオエーテル結合によって ユニークなペプチド構造を作り出しました この過激なS-アデノシルメチオニン (RaS) 酵素は,ペプチドの改変とマクロサイクリングのための自然の方法を拡張します.
科学分野:
- 生物化学
- 自然製品 化学
- 酵素学
背景:
- リボソームで合成されたペプチドと翻訳後のペプチド (RiPP) は,多様な自然産物である.
- 調整酵素は RiPP にユニークな化学機能を導入します.
- RiPP遺伝子群の異常なメタロ酵素は,新しい改変につながる可能性があります.
研究 の 目的:
- 特徴づけられていない過激なS-アデノシルメチオニン (RaS) 金属酵素を含む未調査のRiPP遺伝子クラスタを調査する.
- 新しいRaS酵素,NxxcBの触媒活性について説明する.
- 新しいペプチドマクロサイクリング戦略を特定し,RaS酵素スーパーファミリーのレパートリーを拡張する.
主な方法:
- RiPP遺伝子クラスタを特定するためのバイオ情報検索戦略
- RaS酵素の活性に関する生化学的調査
- 酵素特異性を決定する基質分析
主要な成果:
- 特定されたクオラムセンシング調節されたRiPP遺伝子クラスターと特徴づけられていないRaSメタロ酵素.
- NxxcBは,Cys-thiolをAsn残基のβ-炭素に結合することによって,分子内 β-チオエーテル結合を確立する.
- NxxcBは様々なアミノ酸を受け入れ,非活性化された位置で非自然なβ-チオエーテル結合を生成する.
結論:
- RaS酵素NxxcBによって触媒化された新しいβ-チオエーテル結合の形成を発見した.
- この発見は,既知のペプチドマクロサイクリング戦略を拡張します.
- RaS酵素スーパーファミリーの有意な触媒的汎用性を示しています.
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