胆汁塩ヒドロラーゼ・アシルトランスフェラーゼの活性が胆汁酸の多様性を拡大する
Douglas V Guzior1,2, Maxwell Okros1, Madison Shivel1,3
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Nature
|February 7, 2024
まとめ
研究者らは,腸内細菌の胆汁塩ヒドローラゼ (BSH/T) 酵素が,アミノ酸を胆汁酸 (BA) に結合させ,微生物結合胆汁酸 (MCBA) を生成することを発見した. これらのMCBAは抗菌性を持ち 人間の腸内には豊富に存在します
科学分野:
- 微生物学
- 生物化学
- 腸内微生物群の研究
背景:
- 胆汁酸 (BAs) は,抗菌作用があるため,脂肪の吸収と腸内微生物群の調節に不可欠です.
- 腸内細菌はBAを代謝しますが,アミノ酸結合の特定の酵素とメカニズムはほとんど知られませんでした.
研究 の 目的:
- 腸内微生物群によるBAのアミノ酸結合の原因となる酵素を特定する.
- その結果生じる微生物結合胆酸 (MCBA) の性質と生物学的意義を記述する.
主な方法:
- 様々なアミノ酸とBAを用いたクロストリジウムパーフリンゲンBSH/Tを用いた酵素測定
- 三次構造マッピングと変異性によるBSH/T構造機能関係の分析.
- MCBAの抗菌性テスト
- マウスの体内での研究で,MCBAの肝内循環を追跡した.
- 人間の排泄物のサンプルにおけるMCBAの定量化と,減量手術の結果との相関.
主要な成果:
- 胆汁塩ヒドロラーゼ/トランスファーゼ (BSH/T) という酵素は,アミノ酸をBAに結合させ,多様なMCBAを生成する.
- BSH/Tはアミノ酸の選択性があり,pHは5. 3で最適化される.
- MCBAは抗菌性を持ち,活性度はアミノ酸の性と相関しています.
- MCBAはヒトの腸内において有意な濃度で存在し,減量手術によって影響を受けます.
結論:
- BSH/Tのアシルトランスフェラーゼ活動は,胆酸化学を著しく拡張する.
- MCBAは以前は過小評価されていた 胆汁酸の重要な成分で 微生物群と人間の健康に 潜在的影響を及ぼします
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