Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for -Diazoester Production
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION(2023)
摘要
Azaserine is a bacterial metabolite containing a biologically unusual and synthetically enabling alpha-diazoester functional group. Herein, we report the discovery of the azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery of related gene clusters reveals previously unappreciated azaserine producers, and heterologous expression of the aza gene cluster confirms its role in azaserine assembly. Notably, this gene cluster encodes homologues of hydrazonoacetic acid (HYAA)-producing enzymes, implicating HYAA in alpha-diazoester biosynthesis. Isotope feeding and biochemical experiments support this hypothesis. These discoveries indicate that a 2-electron oxidation of a hydrazonoacetyl intermediate is required for alpha-diazoester formation, constituting a distinct logic for diazo biosynthesis. Uncovering this biological route for alpha-diazoester synthesis now enables the production of a highly versatile carbene precursor in cells, facilitating approaches for engineering complete carbene-mediated biosynthetic transformations in vivo.
更多查看译文
关键词
Azaserine,Biosynthesis,Diazoesters,N-N Bonds,Natural Products
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要