与酸脱酶类酸酶融合的细菌酸环酶的结构见解
Keisuke Fujiyama1, Hiroshi Takagi1, Nhu Ngoc Quynh Vo1
1Natural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.
Chemical science
|August 25, 2025
概括
研究人员阐明了一种新型酸脱酶-酸环酶β (HAD-TCβ) 酶的结构,揭示了一个二元组合,使得酸类生物合成的有效基质道成为可能.
科学领域:
- 生物化学
- 结构生物学
- 酵素学
背景情况:
- 环酶 (TCs) 是自然产品生物合成中的关键酶.
- 非正规的HAD-TCβ酶是一个新发现的类别,结构基础不清楚.
- 德里曼型烯是一种有价值的化合物,具有多种应用.
研究的目的:
- 测定来自*Aquimarina spongiae*的滴醇合成酶 (AsDMS) 的共同晶体结构
- 阐明ASDMS中的TCβ和HAD域的催化机制.
- 了解HAD-TCβ酶的结构功能关系并使蛋白质工程成为可能.
主要方法:
- AsDMS与基质和中间体的共结晶.
- 酶活性测定
- 预测AlphaFold2的结构.
- 活动场所残留物的比较分析.
- 通过向突变发生的合理蛋白质工程.
主要成果:
- 共同晶体结构显示了AsDMS作为一个二元体,促进TCβ和HAD域之间的静电基质通道.
- TCβ 域执行二类循环,而 HAD 域表现出金属依赖性脱.
- 通过AlphaFold2建模和比较分析,可以通过突变发生变的过程将AsDMS从drimenol合成酶转化为albicanol合成酶.
结论:
- AsDMS的二元结构和基质通道机制是有效的drimane型基生物合成的关键.
- 这项研究提供了对HAD-TCβ酶及其催化机制的结构见解.
- 理性蛋白质工程证明了改变HAD-TCβ酶功能的潜力,以产生新的基.
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