モルフォジェネティック・ランチペプチド SapTにおける予期せぬメチランチオニンの立体化学
Raymond Sarksian1, Julian D Hegemann2, Max A Simon3
1Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61822, United States.
Journal of the American Chemical Society
|March 30, 2022
まとめ
研究者らは,リボソームで合成され,翻訳後に改変されたペプチドのクラスであるランチペプチド内のメチランチオニン (MeLan) 残基に新しいステレオ化学を発見した. この発見はランチペプチドの構造と生物活性に関する理解を広げています
科学分野:
- 生物化学
- 分子生物学
- 微生物学
背景:
- ランチペプチドは,ランチオニン (Lan) またはメチランチオニン (MeLan) のクロスリンクを含むリボソーム合成および翻訳後の改変ペプチド (RiPP) である.
- ランチペプチドの生物活性には, (Me) ラン残基のステレオ化学が不可欠である.
- 以前に特徴づけられたランチペプチドは,そのMeLan残基で2S,3Sまたは2R,3Rのステレオ化学を示している.
研究 の 目的:
- エシェリキア・コライのクラスIランチペプチドSapTの生物合成経路を再構成する.
- 異質的に生成された SapT の MeLan 残基のステレオ化学を特徴づける.
- 他のランチペプチドにおける新しい MeLan ステレオ化学の潜在的流行と起源を調査する.
主な方法:
- E. coliにおけるSapT生物合成経路の異質表現
- 立体化学分析のための化学基準の合成
- ランチペプチド生物合成酵素のバイオ情報分析
- サイト・ディレクテッド・ミュータジェネシス 反応メカニズムを検知する
主要な成果:
- E. coliでSapT生物合成経路を成功裏に再構成した.
- SapTで2S,3Rステレオ化学 (d-allo-l-MeLan) で3つのMeLan残基を特定した.これはランチペプチドにとって新しい発見である.
- 生物情報分析とStreptomyces coelicolorにおける実験的検証は,他のランチペプチドにおけるd-allo-l-MeLanの存在を確認した.
- このユニークなステレオ化学の起源を説明するメカニズムを提案し,証拠を提供した.
結論:
- SapTにおけるd-allo-l-MeLanの発見は,ランチペプチドの既知のステレオ化学的多様性を拡大する.
- 生物情報学的および実験的なデータは,このステレオ化学がSapTに特異的ではないことを示し,他のランチペプチドに存在することがあります.
- この研究は,MeLanの形成とランチペプチドの生物合成を制御する酵素機構の洞察を提供します.
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