Institute of Pharmaceutical Biotechnology & First Affiliated Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, China.
School of Chemistry and Chemical Engineering, Henan Normal University, 453007, Xinxiang, China.
Nat Commun. 2019 Oct 8;10(1):4420. doi: 10.1038/s41467-019-12250-1.
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.
偶氮键是一种重要的化学键，在高能密度材料中起着至关重要的作用。然而，偶氮键的生物合成机制仍然是一个谜。在这里，我们报告说，偶氮霉素的偶氮键生物合成是一个酶促和非酶促偶联级联反应。在第一步中，非血红素双核铁氮氧酶 AzoC 催化胺氧化为其亚硝基类似物。氧化还原辅酶对通过自由基瞬变中间体促进亚硝基基团和羟胺之间的相互转化，有效地二聚形成偶氮键。AzoC 中亲核反应性的缺乏被认为是该酶将胺非经典氧化为亚硝基产物的原因。辅酶对诱导的游离氮自由基被认为负责高效的非酶促偶氮键形成。这项机制研究将为偶氮高能密度材料和其他有价值的偶氮化学品的生物合成提供分子基础。
