Molecular mechanism of azoxy bond formation for azoxymycins biosynthesis
Molecular mechanism of azoxy bond formation for azoxymycins biosynthesis
复制标题
阿佐霉素生物合成中偶氮键形成的分子机制
DOI：
10.1038/s41467-019-12250-1
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发表时间：
2019-10-08
影响因子：
16.6
通讯作者：
Li, Yong-Quan
中科院分区：
文献类型：
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作者：
Guo, Yuan-Yang;Li, Zhen-Hua;Li, Yong-Quan
氧化偶氮键是一种重要的化学键，在高能量密度材料中起着至关重要的作用。然而，氧化偶氮键的生物合成机制仍然是个谜。在这里，我们报告的氧化偶氮键的生物合成氧化偶氮霉素是一个酶和非酶偶联级联反应。在第一步中，非血红素二铁N-加氧酶AzoC催化胺氧化成其亚硝基类似物。氧化还原辅酶对促进亚硝基和羟胺之间的相互转化，通过自由基的瞬态中间体，有效地二聚成氧化偶氮键。提出AzoC的亲核反应活性不足是其非典型氧化胺生成亚硝基产物的原因。由辅酶对诱导的自由氮自由基被认为是负责有效的非酶氧化偶氮键的形成。该机理的研究将为合成高能量密度的含氮化合物和其他有价值的含氮化合物提供分子基础。
Azoxy bond is an important chemical bond and plays a crucial role in high energy density materials. However, the biosynthetic mechanism of azoxy bond remains enigmatic. Here we report that the azoxy bond biosynthesis of azoxymycins is an enzymatic and non-enzymatic coupling cascade reaction. In the first step, nonheme diiron N-oxygenase AzoC catalyzes the oxidization of amine to its nitroso analogue. Redox coenzyme pairs then facilitate the mutual conversion between nitroso group and hydroxylamine via the radical transient intermediates, which efficiently dimerize to azoxy bond. The deficiency of nucleophilic reactivity in AzoC is proposed to account for the enzyme's non-canonical oxidization of amine to nitroso product. Free nitrogen radicals induced by coenzyme pairs are proposed to be responsible for the efficient non-enzymatic azoxy bond formation. This mechanism study will provide molecular basis for the biosynthesis of azoxy high energy density materials and other valuable azoxy chemicals.