探索由细胞染色体P450宏酶产生的含比的多样性
Journal of the American Chemical Society
|September 27, 2023
概括
细胞染色体P450酶在核糖体合成和转化后改性 (RiPPs) 中产生多种双链,扩大这些天然产品的化学多样性. 这项研究确定了新的P450宏环酶,并描述了新的含比的,称为.
科学领域:
- 生物化学
- 自然产品生物合成
- 酵素学
背景情况:
- 细胞P450酶 (P450s) 在天然产品生物合成中的氧化交叉合反应中至关重要.
- 在特定的核糖体合成和转化后改性 (RiPPs) 中,P450s形成双宏环链.
- 含有双的宏环RiPP的化学多样性在很大程度上尚未被探索.
研究的目的:
- 研究P450s在RiPPs上产生多种双链的能力,称为"cyptides".
- 发现新型的P450大环和它们所产生的含比.
- 探索细菌基因组中含有双的更广泛的化学空间.
主要方法:
- 使用同质性对P450宏类进行基因组挖掘.
- 在大肠杆菌中P450和前体的异构联合表达
- 对新型含比的NMR结构确定和P450s的生物化学表征.
主要成果:
- 确定了编码P450宏类的19个新型同源生物合成基因集群 (BGC).
- 确定了三种新的含有双的结构:roseovertin (1), rubrin (2) 和 lapparbin (3).
- 证实了前所未有的三种双链接:Trp C-7'-to-His N-τ 在1,Trp C-7'-to-Tyr C-6 在2,和Tyr C-6-to-Trp N-1' 在3. 一些P450表现出放松的基质特异性.
结论:
- P450s可以在RiPPs上产生多种双链接,显著扩大已知的酸的化学多样性.
- 发现了新的P450和独特的双链,突出了它们在创建复杂结构中的进化作用.
- 这项工作为探索细菌基因组中编码的含比的更广泛范围开辟了道路.
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