Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference.
Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference.
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静电相互作用决定胆汁盐水解酶底物偏好。
DOI：
10.1101/2023.09.25.559308
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Chang,PamelaV
中科院分区：
文献类型：
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作者：
Malarney,KienP;Chang,PamelaV
人类肠道由数万亿微生物定殖，包括肠道微生物群，其产生不同的小分子代谢物并修饰宿主代谢物，例如调节宿主生理学的胆汁酸。胆汁酸在肝脏中生物合成，与甘氨酸或牛磺酸缀合并分泌到肠中，在肠中肠道微生物胆汁盐水解酶（BSH）使氨基酸解缀合以产生非缀合胆汁酸，其充当次级胆汁酸代谢物的前体。其中包括最近发现的一类微生物缀合的胆汁酸（MCBA），其中替代氨基酸缀合到胆汁酸上。为了阐明MCBA的代谢潜力，我们进行了详细的动力学研究，以研究BSH对宿主结合胆汁酸和MCBA的偏好。我们确定了一个BSH，具有积极的协同作用，唯一的MCBA含有芳香族侧链。进一步的分子建模和系统发育分析表明，BSH对芳香族MCBA的偏好是由于底物特异性阳离子-π相互作用，预计在人类肠道微生物BSH中广泛存在。
The human intestines are colonized by trillions of microbes, comprising the gut microbiota, which produce diverse small molecule metabolites and modify host metabolites, such as bile acids, that regulate host physiology. Biosynthesized in the liver, bile acids are conjugated with glycine or taurine and secreted into the intestines, where gut microbial bile salt hydrolases (BSHs) deconjugate the amino acid to produce unconjugated bile acids that serve as precursors for secondary bile acid metabolites. Among these include a recently discovered class of microbially conjugated bile acids (MCBAs), wherein alternative amino acids are conjugated onto bile acids. To elucidate the metabolic potential of MCBAs, we performed detailed kinetic studies to investigate the preference of BSHs for host-conjugated bile acids and MCBAs. We identified a BSH that exhibits positive cooperativity uniquely for MCBAs containing an aromatic side chain. Further molecular modeling and phylogenetic analyses indicated that the BSH preference for aromatic MCBAs is due to a substrate-specific cation–π interaction and is predicted to be widespread among human gut microbial BSHs.