不同类型的肠道细菌依赖于的酶产生urolithins
Minwoo Bae1, Xueyang Dong1, Julian Avila-Pacheco2
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
概括
研究人员确定了关键的细菌酶,可以将基酸 (EA) 转化为抗衰老化合物urolithin A. 这一发现将肠道微生物组功能与减少炎症联系起来,特别是在炎症性肠病 (IBD) 中.
科学领域:
- 微生物组研究 微生物组研究
- 酶学 是一种酶学.
- 代谢学 代谢学 代谢学
背景情况:
- 乌罗立A是一种抗衰老和抗炎代谢物,通过复杂的肠道细菌代谢从酸 (EA) 衍生出来.
- 负责EA转化为urolithin A的特定细菌酶在很大程度上仍未确定,这阻碍了对其健康影响的理解.
- 醇脱氧化步骤至关重要,但在化学上具有挑战性,导致多种类型的乌洛生物活性.
研究的目的:
- 为了确定负责基酸 (EA) 的脱化产生乌罗素A的细菌酶.
- 研究这些酶在脱化过程中使用的催化机制.
- 探索乌罗素A生产,肠道微生物组合和炎症性肠病 (IBD) 之间的关联.
主要方法:
- 差异基因表达分析以确定候选酶.
- 厌氧蛋白质的生产和随后的酶测试以确认酶活性.
- 对人类队列的多组学分析,以将基因表达和代谢物水平与IBD状态相关联.
主要成果:
- 确定了两个不同的酶家族 (DMSO减少酶和山丁氧化酶家族) 能够进行区域选择性脱氧化和泌尿酸氨基酸生成.
- 这些酶家族表现出不同的基质要求,表明脱化有不同的催化机制.
- 患有炎症性肠病 (IBD) 的患者表现出尿酸氨酸A水平降低以及编码尿酸氨酸A生成酶的基因.
结论:
- 该研究通过识别关键细菌酶,阐明了乌罗素生产的分子基础.
- 这项研究扩大了参与多代谢的人类肠道微生物组已知的酶谱.
- 减少IBD患者的乌洛丁A产量表明肠道细菌代谢和宿主炎症之间存在联系,可能会影响EA的健康益处.
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