Lichenicidin rational site-directed mutagenesis library: A tool to generate bioengineered lantibiotics
Lichenicidin rational site-directed mutagenesis library: A tool to generate bioengineered lantibiotics
复制标题
DOI：
10.1002/bit.27130
复制
发表时间：
2019-08-08
影响因子：
3.8
通讯作者：
Mendo, Sonia
中科院分区：
文献类型：
--
作者：
Barbosa, Joana;Caetano, Tania;Mendo, Sonia
羊毛硫抗生素是核糖体合成和后修饰的抗菌肽，作为传统抗生素的替代品而出现。地衣菌素对临床相关细菌具有活性，并且它是第一种在革兰氏阴性宿主大肠杆菌中体内完全产生的羊毛硫醚抗生素。在这里，我们提出了地衣菌素突变体库的结果，其中的突变产生的基础上广泛的书目搜索其他羊毛硫抗生素。双肽羊毛硫抗生素的抗菌活性，如地衣菌素，需要两种肽的协同活性。我们建立了一种不需要纯化互补肽就可以筛选生物活性的方法。这是一种廉价、快速和用户友好的方法，可以扩大规模以筛选生物工程双肽羊毛硫抗生素的大型文库。所应用的系统是可靠的和强大的，因为在一般情况下，所获得的结果证实了其他lantibiotics进行的构效关系的研究。
Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that arise as an alternative to the traditional antibiotics. Lichenicidin is active against clinically relevant bacteria and it was the first lantibiotic to be fully produced in vivo in the Gram-negative host Escherichia coli. Here, we present the results of a library of lichenicidin mutants, in which the mutations were generated based on the extensive bibliographical search available for other lantibiotics. The antibacterial activity of two-peptide lantibiotics, as is lichenicidin, requires the synergistic activity of two peptides. We established a method that allows screening for bioactivity which does not require the purification of the complementary peptide. It is an inexpensive, fast and user-friendly method that can be scaled up to screen large libraries of bioengineered two-peptide lantibiotics. The applied system is reliable and robust because, in general, the results obtained corroborate structure-activity relationship studies carried out for other lantibiotics.