Institute of Pharmaceutical Biotechnology and The 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. 2020 Mar 31;11(1):1614. doi: 10.1038/s41467-020-15420-8.
The heterocycle 1,2,3-triazole is among the most versatile chemical scaffolds and has been widely used in diverse fields. However, how nature creates this nitrogen-rich ring system remains unknown. Here, we report the biosynthetic route to the triazole-bearing antimetabolite 8-azaguanine. We reveal that its triazole moiety can be assembled through an enzymatic and non-enzymatic cascade, in which nitric oxide is used as a building block. These results expand our knowledge of the physiological role of nitric oxide synthase in building natural products with a nitrogen-nitrogen bond, and should also inspire the development of synthetic biology approaches for triazole production.
1,2,3-三唑是最通用的化学支架之一，已广泛应用于各个领域。然而，自然界如何构建这个富含氮的环系统仍然未知。在这里，我们报告了含三唑的抗代谢物 8-氮杂鸟嘌呤的生物合成途径。我们揭示其三唑部分可以通过酶促和非酶促级联反应来组装，其中一氧化氮被用作构建块。这些结果扩展了我们对一氧化氮合酶在构建含氮-氮键的天然产物中的生理作用的认识，也应该启发用于三唑生产的合成生物学方法的发展。
