腸内微生物群による胆酸脱酸化のための代謝経路
Masanori Funabashi1,2, Tyler L Grove3, Min Wang1
1Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
Nature
|June 20, 2020
まとめ
研究者らは,二次性胆酸であるデオキシコール酸 (DCA) とリトコール酸 (LCA) の完全な生物合成経路を明らかにした. この画期的な発見により 治療用途の重要な腸内代謝物の 微生物による製造が可能になりました
科学分野:
- 微生物学
- メタボリック・エンジニアリング
- 生物化学
背景:
- 腸内微生物群は,デオキシコール酸 (DCA) やリトコール酸 (LCA) などの二次胆酸を含む必須分子を産生します.
- DCAとLCAは,代謝と病気に影響を及ぼし,宿主の生理に著しく影響を与えますが,それらの生合成経路は不完全でした.
- 遺伝的ツールの欠如は 微生物の二次胆酸生成の調節を妨げました
研究 の 目的:
- DCAとLCAの生物合成経路を完全に解明する.
- 二次性胆酸合成に関与する酵素を特徴づける.
- DCAとLCAの異質生産のための微生物宿主を設計する.
主な方法:
- 酵素経路の無酸素 in vitro 再構成
- コリック酸をDCAに変換する6つの鍵となる酵素の特徴
- *Clostridium sporogenes*におけるDCA/LCA経路の異質表現
主要な成果:
- コーリック酸からDCAへの完全な8段階の経路が確立され,新しいA-Bリング改変戦略が含まれています.
- 6つの酵素のセットは,DCAの合成に必要で十分であると特定された.
- エンジニアリングされた *Clostridium sporogenes* はDCAとLCAを成功裏に生成し,異質経路の発現と制御を示した.
結論:
- この研究は,DCAとLCAのバイオシンセシスの完全な理解を提供します.
- この研究により 微生物による二次胆酸の生成を 工学的に可能にした.
- この発見は様々な疾患における 胆酸のプールの 治療的調節への道を開く.
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