Conserved Enzymatic Cascade for Bacterial Azoxy Biosynthesis

来源 :基础医学系    发布时间 :2024-04-01    浏览次数 :116


Azoxy compounds exhibit a wide array of biological activities and possess distinctive chemical properties. Although there has been considerable interest in the biosynthetic mechanisms of azoxy metabolites, the enzymatic basis responsible for azoxy bond formation has remained largely enigmatic. In this study, we unveil the enzyme cascade that constructs the azoxy bond in valanimycin biosynthesis. Our research demonstrates that a pair of metalloenzymes, comprising a membrane-bound hydrazine synthase and a nonheme diiron azoxy synthase, collaborate to convert an unstable pathway intermediate to an azoxy product through a hydrazine-azo-azoxy pathway. Additionally, by characterizing homologues of this enzyme pair from other azoxy metabolite pathways, we propose that this two-enzyme cascade could represent a conserved enzymatic strategy for azoxy bond formation in bacteria. These findings provide significant mechanistic insights into biological N–N bond formation and should facilitate the targeted isolation of bioactive azoxy compounds through genome mining.

原文链接:Conserved Enzymatic Cascade for Bacterial Azoxy Biosynthesis | Journal of the American Chemical Society (