通过二甲基利三甲基合成酶对4位置换的三甲基的多位列前化
Jeffrey D Rudolf1, Hong Wang, C Dale Poulter
1Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.
Journal of the American Chemical Society
|January 11, 2013
概括
双甲基酸合成酶对于藻类化物生物合成至关重要,它充当了与改性酸的替代基质. 这种酶在多个内环部位上对托进行先化,揭示出一种共同的先化机制.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 自然产品生物合成 自然产品生物合成
背景情况:
- 来自*Claviceps purpurea*的二甲基酸合成酶 (DMATS) 是藻类化物生物合成的关键,在C4处催化酸前化.
- 已知竞争性抑制剂4-甲基三,被用于探测酶活性.
研究的目的:
- 调查DMATS与4-甲基三和二甲基二酸盐的背景活性.
- 描述前化产品,阐明酶的基质特异性和反应机制.
主要方法:
- 使用修改的托芬类似物 (4-甲基托芬,4-甲基托芬,4-氨基托芬) 和二甲基烯酸二酸盐的酶分析.
- 使用核磁共振 (NMR) 谱学,包括1D和2DNMR技术,对prenyl化产品的结构阐明.
主要成果:
- 4-甲基托作为替代基质,通过C3 (正常和反向) 和N1.1的先化产生了四种产品.
- 4-甲基三和4-氨基三也作为替代基质,在C5和C7发生了先化.
- DMATS证明了在印核上的五个不同的位置上具有prenylate的能力,包括正常和反向区域选择性.
结论:
- 广泛的基质特异性和DMATS的多位点化能力支持用于化的解离性电友性化机制.
- 活性部位内的基质定向和电子效应决定了区域选择性和前化类型.
- 为DMATS酶家族的所有成员提出了一种共同的催化机制.
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