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一种新型抗菌脱水非核糖体三肽的发现和生物合成
作者:小柯机器人 发布时间:2020/10/29 15:52:50

近日,英国阿伯丁大学Hai Deng及其研究团队发现并生物合成了一种新型抗菌脱水非核糖体三肽。2020年10月27日,国际知名学术期刊《德国应用化学》在线发表了这一成果。

据研究人员介绍,脱氢丙氨酸(Dha)和脱氢丁胺(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残留物的天然产物经常被发现具有多种生物活性。虽然(Z)-构象在自然界中占主导地位,但到目前为止,仅发现了少数包含(E)-Dhb的代谢产物。

研究人员报告了通过NMR分析和化学合成发现的一种新型抗菌肽albopeptide,它包含两个连续的不饱和残基Dha-(E)-Dhb。其显示出万古霉素耐药性粪肠球菌的窄谱活性。体外生化分析表明,α肽源于非典型的NRPS途径,并具有异常缩合结构域催化的脱水过程。最后,研究人员发现了细菌王国中先前未开发的一组短不饱和肽,并提示了其在细菌中的重要生物学功能。
 
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

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx