Molecular basis for chloronium-mediated meroterpene cyclization - Cloning, sequencing, and heterologous expression of the napyradiomycin biosynthetic gene cluster
Molecular basis for chloronium-mediated meroterpene cyclization - Cloning, sequencing, and heterologous expression of the napyradiomycin biosynthetic gene cluster
复制标题
DOI：
10.1074/jbc.m611046200
复制
发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Moore, Bradley S.
中科院分区：
文献类型：
--
作者：
Winter, Jaclyn M.;Moffitt, Michelle C.;Moore, Bradley S.
对属于氯化二氢醌萘霉素家族的细菌类萜类抗生素的结构检查表明，其萜类亚基的生物合成环化是通过氯离子启动的。催化此类反应的钒依赖性卤过氧化物酶分布在真菌和海藻中，但尚未从细菌中进行表征。来自 Streptomyces aculeolatus NRRL 18422 和未描述的海洋沉积物来源的 Streptomyces sp. 的 43-kb 萘吡霉素生物合成簇 (nap) 的克隆和序列分析。 CNQ-525 揭示了 33 个开放阅读框，其中三个可能编码钒依赖性氯过氧化物酶。基于CNQ-525的nap生物合成簇在白色链霉菌中的异源表达产生了至少七种萘霉素，包括新的类似物2-脱氯-2-羟基-A80915C。这些数据不仅揭示了这些新型类萜天然产物生物合成背后的分子基础，而且首次在体内验证了钒依赖性卤过氧化物酶。
Structural inspection of the bacterial meroterpenoid antibiotics belonging to the napyradiomycin family of chlorinated dihydroquinones suggests that the biosynthetic cyclization of their terpenoid subunits is initiated via a chloronium ion. The vanadium-dependent haloperoxidases that catalyze such reactions are distributed in fungi and marine algae and have yet to be characterized from bacteria. The cloning and sequence analysis of the 43-kb napyradiomycin biosynthetic cluster ( nap) from Streptomyces aculeolatus NRRL 18422 and from the undescribed marine sediment-derived Streptomyces sp. CNQ-525 revealed 33 open reading frames, three of which putatively encode vanadium-dependent chloroperoxidases. Heterologous expression of the CNQ-525-based nap biosynthetic cluster in Streptomyces albus produced at least seven napyradiomycins, including the new analog 2-deschloro-2-hydroxy-A80915C. These data not only revealed the molecular basis behind the biosynthesis of these novel meroterpenoid natural products but also resulted in the first in vivo verification of vanadium-dependent haloperoxidases.