由真菌聚基酶和弗拉依赖单氧酶催化的烯聚基循环
Shu-Shan Gao1, Abing Duan1, Wei Xu1
1Department of Chemical and Biomolecular Engineering and ‡Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
研究人员发现了合成类天然产品的新途径. 他们发现了一些关键的酶,包括独特的多基合成酶和单氧化酶,
科学领域:
- 自然产品的生物合成
- 多基化工学
- 酵素学
背景情况:
- 类是具有复杂结构和生物活动的天然产品.
- 它们的核心结构是通过不寻常的线性多基前体循环形成的.
- 这种循环的确切机制在很大程度上仍未解决.
研究的目的:
- 阐明的生物合成途径和不寻常的循环机制.
- 确定参与核形成的特定酶.
- 了解这些酶在多基循环中的催化作用.
主要方法:
- 基因组分析以确定Penicillium herquei中的phn生物合成基因集群.
- 非还原聚基酶 (NR-PKS) PhnA的生物化学表征
- 对PhnA和FAD依赖单氧酶 (FMO) PhnB的酶定量和产品分析.
- 密度函数理论 (DFT) 计算以建模反应机制.
主要成果:
- 鉴定了phn基因集群,并表明PhnA可以合成甲基骨架并将其循环转化为前烯.
- PhnA的产品模板 (PT) 域独特地催化了阿尔多尔凝结.
- PhnB被确定为一种同时进行C2芳化和γ-皮龙环开放的FMO.
- DFT计算支持一种新的氧化循环机制来形成烯.
结论:
- 新的生物合成路径和生物催化剂已被发现.
- 这项研究揭示了多基生物合成中前所未有的酶机制.
- 这项工作为理解和工程生产提供了基础.
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