一种flavin-monooxygenase催化剂,催化氧皮的形成和vibralactone的完整生物合成
Ke-Na Feng1, Yue Zhang1,2, Mingfang Zhang3,2
1State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Nature communications
|June 10, 2023
概括
研究人员确定了酶VibO,一个关键的单氧酶,负责在天然产品1,5-seco-vibralactone生物合成中创建不寻常的oxepinone环. 这一发现揭示了复杂的自然产品的形成.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- 氧皮环是天然产品中不常见的结构图案.
- 像在1,5-seco-vibralactone中发现的oxepinones的生物合成,仍然不太了解.
- 在振动乳素生物合成中的4-基酸盐中形成的oxepinone环的起源是一个关键的未回答的问题.
研究的目的:
- 为了阐明1,5-seco-vibralactone中oxepinone环的生物合成途径.
- 为了确定负责环扩张氧化步骤的酶.
- 描述已识别的酶的结构和机制.
主要方法:
- 活动指导的Boreostereum vibrans真菌培养的分化.
- 蛋白质组分析以确定候选酶.
- 生物化学测试以确认酶功能.
- 进行X射线晶体学以确定酶结构.
- 计算建模用于机械洞察力.
主要成果:
- 确定了VibO,一个依赖NADPH/FAD的单氧化酶,作为关键酶.
- 在环上,VibO催化了环膨胀氧化,形成了oxepin-2-one结构.
- 确定了VibO的晶体结构,揭示了具有独特基质结合口袋的二元醇氧酶样结构.
- 计算研究表明,在催化机制中,flavin-C4a-OO(H) 是一种中间体.
结论:
- VibO是负责oxepinone生物合成中的关键环扩张的酶.
- 对VibO的结构和机制洞察力为理解这种不寻常的酶转化提供了基础.
- 这项工作显著提升了我们对涉及oxepinone动机的天然产品生物合成的理解.
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