肠道微生物组相关结肠癌的分子基础:一种合成的视角
Alan R Healy1,2, Seth B Herzon1,3
1Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
Journal of the American Chemical Society
|September 27, 2017
概括
研究人员研究了与结直肠癌相关的细菌代谢物, 合成和生物合成研究表明,菌素是基因毒性胺基因,证实了它们的DNA破坏机制.
科学领域:
- 微生物学
- 自然产品化学
- 人类健康
背景情况:
- 确立细菌代谢物与人类健康之间的因果关系是具有挑战性的.
- 大肠杆菌通过clb基因产生前大肠杆菌素和大肠杆菌素.
- 科利巴克丁被怀疑与结直肠癌有关.
研究的目的:
- 阐明CLB代谢物的结构和作用机制.
- 在理解这些化合物方面利用近期的合成和生物合成进步.
- 确认活性大肠杆菌素的基因毒性和化学类.
主要方法:
- 利用遗传方法研究clb基因及其产物.
- 通过生物合成的洞察力,利用合成化学的努力.
- 研究了删除 colibactin 酶 ClbP 的影响.
主要成果:
- 删除ClbP会导致非基因毒性基化合物.
- 活性基因毒素 (colibactins) 被认为是不和的 imines.
- 这些imine是强大的DNA破坏剂, 证实了先前的假设.
- 在细菌提取物中检测imine是最近的,并且隔离仍然具有挑战性.
结论:
- 最近的合成和生物合成研究澄清了clb代谢物的作用机制.
- 科利巴克被证实是导致DNA损伤的基因毒性不和胺.
- 合成和生物合成研究之间的相互作用对于未来的天然产品发现至关重要.
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