达克沙丁合成酶催化了6 - - 罗格拉尼尔 - - 拉尼尔 - - 二酸盐的循环转化为7 - - 罗维特基烯
Yinghua Jin1, David C Williams, Rodney Croteau
1Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Journal of the American Chemical Society
|May 26, 2005
概括
这项研究研究了使用化基质模拟剂的纳税二烯合成酶的机制. 结果提供了强有力的证据,证明了纳税生物合成中的关键碳酸中间体的立体化学.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 酶学 是一种酶学.
背景情况:
- 纳二烯合成酶催化基兰二酸盐 (GGPP) 到纳二的循环化.
- 拟议的机制涉及一个垂直基基化介质和一个关键的质子转移.
- 了解这种机制对于纳税生物合成和潜在的药物开发至关重要.
研究的目的:
- 阐明了纳二烯合成酶催化过程中的垂基基化介质的立体化学.
- 为了研究替代剂对循环化级联的作用.
- 为拟议反应机制提供令人信服的证据.
主要方法:
- 合成一个基质模拟物,6-fluoroGGPP.
- 用复合式纳税合成酶化光类比物.
- 使用气体染色学-质谱学 (GC/MS) 和核磁共振 (NMR) 光谱学分析产品.
- 使用核重复效应 (NOE) 实验和循环二元化 (CD) 频谱确定立体化学.
- 用X射线晶体学来确定绝对配置.
主要成果:
- 化6-GGPP产生了化二烯的混合物.
- 鉴定出了三种主要的7 - 甲基烯异构体.
- 立体化学的verticillenyl碳酸介质被确立为H11alpha (11R).
- 经过修订,对verticillane diterpenes的绝对配置进行了修订,这表明在文献中需要进行反转.
结论:
- 这项研究提供了令人信服的证据,支持了taxadiene synthase的拟议机制.
- 乙烯类相似物是拦截复杂循环级联的有效工具.
- 这些发现澄清了酶反应的立体化学结果,并修改了现有的结构赋值.
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