肠道微生物体对胆汁酸脱氧的代谢途径
Masanori Funabashi1,2, Tyler L Grove3, Min Wang1
1Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
Nature
|June 20, 2020
概括
研究人员阐明了二次胆汁酸脱氧胆汁酸 (DCA) 和胆汁酸 (LCA) 的完整生物合成途径. 这一突破使得工程微生物能够生产这些关键的肠道代谢物,
科学领域:
- 微生物学
- 代谢工程
- 生物化学
背景情况:
- 肠道微生物群产生必需的分子,包括二次胆酸,如脱氧胆酸 (DCA) 和石胆酸 (LCA).
- DCA和LCA显著影响宿主生理,影响新陈代谢和疾病,但它们的生物合成途径尚不完全理解.
- 缺少遗传工具阻碍了微生物的二次胆酸产生.
研究的目的:
- 为了充分阐明DCA和LCA的生物合成途径.
- 描述参与二次胆酸合成的酶.
- 设计微生物宿主用于DCA和LCA的异构生产.
主要方法:
- 酶途径的无氧 in vitro 复制
- 用于将胆酸转化为DCA的六个关键酶的表征.
- 在 *Clostridium sporogenes* 中的DCA/LCA通路的异构表达.
主要成果:
- 建立了从胆酸到DCA的完整八步路径,涉及一种新的A-B环修饰策略.
- 一组六种酶被确定为DCA合成的必要和足够.
- 工程化*Clostridium Sporogenes*成功地产生了DCA和LCA,证明了异构路径的表达和控制.
结论:
- 这项研究提供了对DCA和LCA生物合成的全面了解.
- 这项工作使微生物产生二次胆汁酸的工程成为可能.
- 这些发现为治疗各种疾病中的胆酸池开辟了道路.
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