揭示了Sphaerols A-E的生物合成:由两个不常见的迪特尔合成酶AsSS和CvSS催化
Gui-Hu Lu1, Zhe-Hui Hu2, Ping-Ping Wu1
1Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Organic letters
|April 1, 2025
概括
两种细菌二二烯合成酶,AsSS和CvSS,被发现并用于合成新型球蛋白A和B. 确定了用于立体选择性化的关键氨基酸残留物,使功能性酶相互转换成为可能.
科学领域:
- 生物化学 生化学
- 有机化学 有机化学
- 酶学 是一种酶学.
背景情况:
- 迪特尔合成酶对于产生具有多种生物活动的迪特尔类物质至关重要.
- 发现新的二二烯合成酶为探索新的化学支架提供了机会.
研究的目的:
- 发现和描述两个罕见的细菌二二烯合成酶,AsSS和CvSS.
- 合成和阐明由这些酶产生的新型二甲的结构.
- 研究作用机制和参与酶反应的关键残留物.
主要方法:
- 细菌二二烯合成酶 (AsSS和CvSS) 的分离和表征.
- 使用光谱数据和量子化学计算,化学合成和阐明甲基和乙基的结构.
- 机械学研究涉及同位素标记和密度函数理论 (DFT) 计算.
- 位点定向突变发生 (氨基酸残留物交换) 以确定关键的功能残留物.
主要成果:
- 在细菌中发现了两种新的二二烯合成酶,AsSS和CvSS,具有低序列相同性 (26%) .
- 合成甲基和乙基球醇,具有独特的重新排列支架和明显的C-7氧化.
- 通过同位素标记和DFT计算验证拟议的循环化机制.
- 确定AsSS-M81和CvSS-C82作为对立体选择性C-7氧化过程的关键残留物.
- 在AsSS和CvSS之间成功实现了功能互换.
结论:
- 这项研究揭示了能够产生独特的二基结构的新型二基合成酶.
- 确定了控制基化中的立体选择性的关键氨基酸残留物.
- 实现了这些酶的功能性相互转换,证明了它们的可塑性.
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