• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >P450 monooxygenase ComJ catalyses side chain phenolic cross-coupling during complestatin biosynthesis
【24h】

P450 monooxygenase ComJ catalyses side chain phenolic cross-coupling during complestatin biosynthesis

机译：P450单加氧酶ComJ催化补全他汀生物合成过程中的侧链酚类交叉偶联

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Complestatin is a non-ribosomal heptapeptide belonging to the glycopeptide antibiotic family that displays anti-complement, anti-HIV integrase, neuroprotective, anti-apoptotic, and antibacterial activities. Development of complestatin as a pharmaceutical agent and biological probe has been stymied by the difficulty in isolating the molecule from its natural source, Streptomyces lavendulae, as well as by the uneconomical and environmentally unfriendly nature of current total synthetic routes. Of particular challenge to the organic chemist is the installation of the biaryl and aryl–ether–aryl linkages that provide complestatin with the structural rigidity responsible for its potent pharmacological properties. Herein, we demonstrate that ComJ, a P450 monooxygenase from the complestatin biosynthetic gene cluster, can catalyse phenolic cross-linking of amino acid side chains in vitro. ComJ acts with high efficiency and low substrate stereoselectivity, a finding which paves the way towards the use of ComJ as a biocatalyst for the chemo-enzymatic synthesis of complestatin and other related molecules. The ability of ComJ to accept peptides of alternative stereochemistries raises intriguing questions about the evolutionary origins of glycopeptide antibiotic biosynthesis and the capacity of S. lavendulae to produce different conformations of complestatin.
机译：Complestatin是属于糖肽抗生素家族的非核糖体七肽，具有抗补体，抗HIV整合酶，神经保护，抗凋亡和抗菌活性。由于难以从天然来源的薰衣草链霉菌中分离出该分子，以及目前的全合成途径的经济性和环境不友好性，阻碍了补菌素作为药物和生物探针的开发。有机化学家面临的特别挑战是如何安装联芳基和芳基-醚-芳基键合，从而使补全他汀具有强大的药理学特性。在本文中，我们证明了ComJ，一种来自complestatin生物合成基因簇的P450单加氧酶，可以在体外催化氨基酸侧链的酚类交联。 ComJ具有高效率和低底物立体选择性的作用，这一发现为将ComJ用作化学酶合成complestatin和其他相关分子的生物催化剂铺平了道路。 ComJ接受替代立体化学肽的能力提出了有关糖肽抗生素生物合成的进化起源和 S的能力的有趣问题。 lavendulae 产生不同构型的Complestatin。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号