代谢性 thiolase 复合物的进化重定位使抗生素生物合成成为可能
Ge Liao1, Ruolan Sun1,2,3, Zilin Shen4,5
1Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
Nature communications
|January 30, 2026
概括
科学家们在口腔细菌中发现了一种新型的酶复合物,该复合物重新利用其祖先的功能来创造抗生素reutericyclin A. 这一发现揭示了酶的罕见进化路径,并为合成生物学提供了新的工具.
科学领域:
- 生物化学 生化学
- 酵素进化 酵素进化
- 自然产品生物合成 自然产品生物合成
背景情况:
- 主要代谢酶进化为二次代谢途径的过程尚不清楚.
- 由于酶的功能多样化,天然产品表现出不同的化学结构.
研究的目的:
- 为了研究负责口腔链球菌种类中reutericyclin A生物合成的酶复合物.
- 为了阐明这个三方酶复合体的进化轨迹和催化机制.
主要方法:
- 低温电子显微镜 (Cryo-EM) 用于确定复合物的结构.
- 生物化学表征来分析酶活性.
- 分子建模和进化分析以了解功能变化.
主要成果:
- 确定了一种三方酶复合物 (HMGS,ACAT,DUF35),催化Friedel-Crafts C-乙化用于reutericyclin A合成.
- 该综合体与古老的甲基酸盐通路酶具有共同的结构,但已经重新连接了催化残留物.
- 祖先的HMG-CoA合成活动丢失;该复合物为形成C-C键的新功能化.
结论:
- 这项研究提供了一个罕见的 thiolase 复合物新功能化的例子.
- 这些发现揭示了酶进化的研究不足的领域.
- 重新利用的酶复合物作为工程 C-C 键形成催化剂的模板.
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