Herbicidins are adenosine-derived nucleoside antibiotics with an unusual tricyclic core structure. Deletion of the genes responsible for formation of the tricyclic skeleton in Streptomyces sp. L-9-10 reveals the in vivo importance of Her4, Her5, and Her6 in the early stages of herbicidin biosynthesis. In vitro characterization of Her4 and Her5 demonstrates their involvement in an initial, two-stage C–C coupling reaction that results in net C5′-glycosylation of ADP/ATP by UDP/TDP–glucuronic acid. Biochemical analyses and intermediate trapping experiments imply a noncanonical mechanism of C-glycosylation reminiscent of NAD-dependent S-adenosylhomocysteine (SAH)-hydrolase catalysis. Structural characterization of the isolated metabolites suggests possible reactions catalyzed by Her6 and Her7. An overall herbicidin biosynthetic pathway is proposed based on these observations.

中文翻译：

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鉴定除草素生物合成的早期步骤揭示了 C-糖基化的非典型机制

除草素是腺苷衍生的核苷类抗生素，具有不寻常的三环核心结构。缺失链霉菌中负责形成三环骨架的基因。L-9-10 揭示了Her4、Her5 和 Her6 在除草素生物合成早期的体内重要性。Her4和 Her5 的体外表征表明它们参与了初始的两阶段 C-C 偶联反应，导致 UDP/TDP-葡萄糖醛酸对 ADP/ATP 的净 C5'-糖基化。生化分析和中间捕获实验暗示C -糖基化的非规范机制让人想起 NAD 依赖性S-腺苷高半胱氨酸（SAH）-水解酶催化。分离代谢物的结构表征表明 Her6 和 Her7 催化的可能反应。基于这些观察提出了整体除草素生物合成途径。