Department of Biology & Centre for Environmental and Marine Studies (CESAM), University of Aveiro, Aveiro, Portugal.
Institut für Chemie, Technical University of Berlin, Berlin, Germany.
Biotechnol Bioeng. 2019 Nov;116(11):3053-3062. doi: 10.1002/bit.27130. Epub 2019 Aug 8.
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.
类杆菌素是核糖体合成和翻译后修饰的抗菌肽，是传统抗生素的替代品。地衣芽孢菌素对临床相关细菌具有活性，它是第一个在革兰氏阴性宿主大肠杆菌中体内完全产生的类杆菌素。在这里，我们展示了一个类杆菌素突变体文库的结果，其中的突变是基于其他类杆菌素的广泛文献搜索生成的。两肽类杆菌素（如地衣芽孢菌素）的抗菌活性需要两种肽的协同作用。我们建立了一种筛选方法，该方法不需要纯化互补肽就能检测生物活性。它是一种廉价、快速且用户友好的方法，可以扩展到筛选大量生物工程两肽类杆菌素文库。所应用的系统是可靠和强大的，因为一般来说，获得的结果与针对其他类杆菌素进行的结构-活性关系研究相符。
