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胆汁塩ヒドローラゼは,アミン結合胆汁酸の形成を触媒する

Bipin Rimal¹, Stephanie L Collins², Ceylan E Tanes³

¹Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA.

|February 7, 2024

まとめ

腸内細菌は,胆塩ヒドローラゼ (BSH) という酵素を用いて,バクテリア胆酸アミデット (BBA) と呼ばれる新しい化合物を生成する. これらのBBAは,重要な転写因子を活性化することによって宿主の代謝に影響を与えます.

科学分野:

微生物学
メタボリック・エンジニアリング
ホストと微生物の相互作用

背景:

胃腸バクテリアは,宿主の代謝に影響を与えるアミノ酸胆酸アミドを生成する.
これらのアミダートを生成する特定の細菌の遺伝子は未確認のままである.
胆酸代謝は宿主の生理学的プロセスに不可欠です.

研究の目的:

アミノ酸の胆酸アミド酸を生成するバクテリアの遺伝子を特定する.
アミダート形成における胆塩ヒドローラゼ (BSH) の新しい酵素活性を示す.
細菌の胆酸アミダート (BBAA) が宿主転写因子に及ぼす影響を調査する.

主な方法:

薬学的にBSHを抑制した.
エシェリキア・コライにおける bsh とその変異体の異質表現を用いた.
Bacteroides fragilisで bsh ノックアウトと補完研究を実施した.
BBAAの産生とバクテリアの植民を分析した.
細胞培養モデルにおける宿主転写因子のBBAA活性化試験

主要な成果:

胆汁塩ヒドロラーゼ (BSH) は,アミンを胆汁酸に結合させ,バクテリア胆汁酸アミド酸 (BBAAs) を形成するアミンN-アシルトランスフェラーゼである.
遺伝子と薬理学的アプローチを通じてBBAA生成におけるBSHの役割を実証した.
ヒトの乳児におけるBBAA産生とbsh発現する細菌のコロニー化との正の相関が観察された.
細胞培養において,pregnane X受容体およびアリル炭水化物受容体を含む宿主転写因子を活性化することを示した.

結論:

胆汁塩ヒドロラーゼ (BSH) は,胆汁酸代謝において,ヒドロラーゼとアミンN-アシルトランスフェラーゼの両方として作用する.
腸内細菌は,BSHの乱れた活動を通じて,胆酸代謝ネットワークに大きく貢献します.
細菌胆酸アミダート (BBAA) は,宿主信号伝達経路を調節できる新種の代謝産物である.

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