在Paraherquamide生物合成途径中形成螺旋环的分子基础
Amy E Fraley, Kersti Caddell Haatveit1, Ying Ye
1Department of Chemistry and Biochemistry , University of California , Los Angeles , California 90095 , United States.
Journal of the American Chemical Society
|January 7, 2020
概括
研究人员阐明了帕赫奎米德生物合成中的关键螺旋循环化步骤,由弗拉单氧基酶PhqK催化. 这项研究揭示了PhqK如何选择性地形成复杂的结构,这对强烈的虫作用至关重要.
科学领域:
- 自然产品生物合成
- 酵素学
- 有机化学
背景情况:
- 帕赫克瓦米德是具有复杂的七环基架的强效杀虫剂.
- 一个关键的结构特征是螺旋-oxindole部分,有助于他们的紧张的三维架构.
研究的目的:
- 阐明甲胺生物合成中flavin单氧酶PhqK的机制和基质选择性.
- 了解选择性螺旋循环过程对于产生这些虫剂至关重要.
主要方法:
- 从Penicillium simplicissimum的ΔphqK突变菌株中分离出新的甲胺 (K和L).
- 酶反应产生进一步的代谢物 (M和N).
- 使用基质的X射线晶体学,机械分析和分子动力学模拟.
主要成果:
- 通过两条并行途径在甲基胺A和G生物合成中催化螺旋环形成.
- 鉴定了K和L类甲基,并通过酶生成M和N类甲基.
- 晶体结构和模拟揭示了PhqK的基质相互作用,有利于含有二氧化的帕赫奎米德L.
结论:
- 已经阐明了帕赫奎米德生物合成中的一个关键步骤,涉及PhqK介导的螺旋循环.
- 这项研究为选择性形成这些强烈的杀虫剂化合物提供了机理性见解和理由.
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