Discovery and biosynthetic investigation of a new antibacterial dehydrated non-ribosomal tripeptide.
Discovery and biosynthetic investigation of a new antibacterial dehydrated non-ribosomal tripeptide.
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DOI：
10.1002/anie.202012902
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发表时间：
2020-10
影响因子：
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通讯作者：
Shan Wang;Qing Fang;Zhou Lu;Yingli Gao;L. Trembleau;R. Ebel;J. H. Andersen;Carol Philips;Samantha Law;Hai Deng
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文献类型：
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作者：
Shan Wang;Qing Fang;Zhou Lu;Yingli Gao;L. Trembleau;R. Ebel;J. H. Andersen;Carol Philips;Samantha Law;Hai Deng
脱氢丙氨酸（Dha）和脱氢丁酸（Dhb）在各种化学和生物反应中显示出相当大的灵活性。含有Dha和/或Dhb残基的天然产物通常被发现具有多种生物活性。虽然（Z）-几何结构在自然界中占主导地位，但迄今为止仅发现少数含有（E）-Dhb的代谢物。本文报道了通过核磁共振分析和化学合成发现的一种新的抗菌肽--白肽，它含有两个相邻的不饱和残基Dha-（E）-Dhb。它对万古霉素耐药屎肠球菌显示窄谱活性。体外生化分析表明，白肽来源于一个非经典的NRPS途径，脱水过程的特点，不寻常的缩合域催化。最后，我们提供的证据，以前未开发的一组短的不饱和肽在细菌王国的发生，这表明在细菌中的重要的生物功能。
Dehydroalanine (Dha) and dehydrobutyrine (Dhb) display considerable flexibility in a variety of chemical and biological reactions. Natural products containing Dha and/or Dhb residues are often found to possess diverse biological activities. While the ( Z )-geometry is predominant in nature, only a handful of metabolites containing ( E )-Dhb have been found thus far. Here we report discovery of a new antimicrobial peptide, albopeptide, through NMR analysis and chemical synthesis, which contains two contiguous unsaturated residues, Dha-( E )-Dhb. It displays narrow-spectrum activity against vancomycin-resistant Enterococcus faecium. In vitro biochemical assays show that albopeptide originates from a noncanonical NRPS pathway, featured with dehydration processes, catalysed by unusual condensation domains. Finally, we provide evidence of the occurrence of a previously untapped group of short unsaturated peptides in the bacterial kingdom, suggesting an important biological function in bacteria.