由肠道微生物群表达的多种酶可以转化类型,并与改善超脂血症有关
Hui Xu1, Ru Feng1, Meng-Liang Ye1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, 100050, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|January 22, 2025
概括
这项研究揭示了肠道微生物如何使用多种酶代谢类菌素 (TYP),识别了诸如α-rhamnosidase和β-glucosidase之类的关键酶. 由此产生的代谢产物显示出显著的降脂效应,为自然的黄类代谢提供了洞察力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 微生物学 微生物学
- 生物化学 生物化学
背景情况:
- 肠道微生物群对类甲酸 (TYP) 的代谢及其降脂机制尚不清楚.
- 作为Typha angustifolia L.和Pushen囊的成分,TYP的生物利用率很低 (2.78%),但用于高脂血症.
研究的目的:
- 阐明TYP在肠道微生物群中的多酶介导的代谢途径.
- 为了确定参与TYP代谢的关键酶.
- 评估TYP代谢产物在降低脂质方面的药理活性.
主要方法:
- 在大肠杆菌中使用基因淘汰和过度表达技术来验证酶功能.
- 代谢物识别和分析.
- 分子对接模拟. 分子对接模拟.
- 在体内实验中评估抗高脂血症疗效.
主要成果:
- 过度表达的α-rhamnosidase (Rha) 将TYP转化为M1和M2,通过去除rhamnose.
- 绝杀β-葡萄糖酶 (Glu) 通过去除葡萄糖证实了TYP转化为M3.
- 分子对接揭示了M3通过黄减酶 (Flr) 和石墨烯异构酶 (Chi) 进一步代谢成M4,M5和M6.
- 结合M3和M5在体内显示出显著的抗高脂血症效应.
结论:
- 确定了一种新的多酶途径 (Rha/Glu→Flr→Chi),用于肠道微生物群中的TYP代谢.
- 这项研究首次全面了解了由多种酶介导的复杂的天然黄类代谢.
- 这些发现为研究类似的天然产品和开发新的超脂血症治疗方法提供了宝贵的见解.
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