晶体结构和催化机制的cis-Eunicellane循环AriEE
Fang-Ru Li1, Qian Yang1, Jingyi He1
1State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Chemistry (Weinheim an der Bergstrasse, Germany)
|April 23, 2025
概括
研究人员解决了cis-eunicellane cyclase (AriE) 的结构,揭示了它如何形成特定的二形结构. 变异性研究表明如何设计这些酶以形成多样化或选择性的烯产品.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 欧尼塞兰二类是具有多种生物活性的大型自然产品类.
- 现有的单环类 (ECs) 属于 cis-和 trans-forming 族,但它们的结构基础仍然不清楚.
研究的目的:
- 阐明cis-eunicellane环酶 (EC) 活性的结构基础.
- 了解控制 cis-cyclization 的分子机制.
- 探索工程ECs用于新型diterpenoid生产.
主要方法:
- 在1.87 Å分辨率的AriE (a cis-EC) 的X射线晶体学.
- 关键残留物的结构导向的位点导向突变发生 (W73,Y203).
- 通过野生类型和突变酶产生的二烯产品的分析.
主要成果:
- 确定了AriE的晶体结构,这是一种来自Amycolatopsis arida的cis-EC.
- 残留物W73的突变发生揭示了其在控制产品多样性的作用.
- 突变Y203将AriE转化为一种特定的 (-) - ((R) -cembrene A合成酶.
结论:
- 这项研究提供了关于cis-eunicellane 循环级的第一个结构见解.
- 这些发现表明,工程EC可以导致选择性四形形成.
- 这项工作为生物催化生产有价值的烯开辟了道路.
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