一种多功能C-C和C-N键形成的Diketopiperazine Dimerase的结构和功能
Vikram V Shende, Yogan Khatri, Sean A Newmister
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|August 14, 2020
概括
研究人员发现了一种新型酶,NzeB,可以选择性地产生复杂的二聚二烯酸. 这一发现为合成这些天然产品提供了新的生物催化方法,
科学领域:
- 自然产品合成
- 酵素学
- 结构生物学
背景情况:
- 滴度二甲酸 (DKPs) 是具有复杂结构和有价值的生物活性的天然产品.
- 现有的合成方法无法控制从单个单体中选择性形成构造性和立体异构的DKPs.
- 使用酶的生物催化方法为控制的DKP合成提供了有希望的途径.
研究的目的:
- 用于组装生物催化剂的生物合成酶的特征.
- 了解NzeB的催化灵活性和选择性的分子基础.
- 为NzeB在DKP二元化中的功能提供结构和计算的理由.
主要方法:
- 从Streptomyces sp中识别NzeB酶的基因组挖掘 这就是NRRL F-5053.
- 用各种基板测定NzeB的高分辨率晶体结构 (1.5 Å).
- 位点定向突变检测活性位点残留物的功能.
- 计算机建模以阐明反应机制.
主要成果:
- 一个P450细胞染色体NzeB在DKP合成中催化碳-碳 (C-C) 和碳- (C-N) 键的形成.
- 晶体结构揭示了NzeB灵活的位置,立体和化学选择性的分子基础.
- 这是氧化酶催化直接分子间C-H氨基化的第一个晶体结构.
- 突变和计算研究提供了对残留物导向选择性的见解.
结论:
- NzeB具有显著的催化灵活性,使得选择性DKP二元化成为可能.
- 结构和计算数据为NzeB独特的催化能力提供了理由.
- 这项研究有助于更好地了解CYP450二甲二酶,并为合成化学提供了工具.
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