一種新型抗菌脫水非核糖體三肽的發現和生物合成

一種新型抗菌脫水非核糖體三肽的發現和生物合成

作者：

小柯機器人

發布時間：2020/10/29 15:52:50

近日，英國阿伯丁大學Hai Deng及其研究團隊發現並生物合成了一種新型抗菌脫水非核糖體三肽。2020年10月27日，國際知名學術期刊《德國應用化學》在線發表了這一成果。

據研究人員介紹，脫氫丙氨酸（Dha）和脫氫丁胺（Dhb）在各種化學和生物反應中顯示出相當大的靈活性。含有Dha和/或Dhb殘留物的天然產物經常被發現具有多種生物活性。雖然(Z)-構象在自然界中佔主導地位，但到目前為止，僅發現了少數包含(E)-Dhb的代謝產物。

研究人員報告了通過NMR分析和化學合成發現的一種新型抗菌肽albopeptide，它包含兩個連續的不飽和殘基Dha-(E)-Dhb。其顯示出萬古黴素耐藥性糞腸球菌的窄譜活性。體外生化分析表明，α肽源於非典型的NRPS途徑，並具有異常縮合結構域催化的脫水過程。最後，研究人員發現了細菌王國中先前未開發的一組短不飽和肽，並提示了其在細菌中的重要生物學功能。

 

附：英文原文

Title: Discovery and biosynthetic investigation of a new antibacterial dehydrated non‐ribosomal tripeptide

Author: Shan Wang, Qing Fang, ZHOU LU, Yingli GAO, Laurent Trembleau, Rainer Ebel, Jeanette H Andersen, Carol Philips, Samantha Law, Hai Deng

Issue&Volume:

Abstract: 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.

DOI: 10.1002/anie.202012902

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202012902