PDF(Pubmed)
Abstract：
Lantibiotics are believed to have a conceivable potential to be used as therapeutics, especially against clinically resistant bacterial strains. However, their low solubility and poor stability under physiological conditions limit their availability for clinical studies and further pharmaceutical commercialization. Nisin is a readily available and cheap lanthipeptide and thus serves as a good model in the search for the tools to engineer lantibiotics with improved pharmacological properties. This review aims to address technologies that can be applied to alter and enhance the antimicrobial activity, antibacterial spectrum and physicochemical properties (solubility, solution stability and protease resistance) of nisin. There are basically two general means to obtain nisin analogs-protein engineering and chemical functionalization of this antibiotic. Although bioengineering techniques have been well developed and enable the creation of nisin mutants of variable structures and properties, they are lacking spectacular effects so far. Chemical modifications of nisin based on utilization of the reactivity of its free amino and carboxylic moieties, as well as reactivity of the double bonds of its dehydroamino acids, are in their infancy.
摘要：
低硫抗生素被认为有可能被用作治疗药物，特别是针对临床耐药菌株。然而,它们在生理条件下的低溶解度和差的稳定性限制了它们用于临床研究和进一步的药物商业化。Nisin是一种容易获得且廉价的羊毛硫肽，因此在寻找设计具有改善的药理特性的抗生素的工具中用作良好的模型。这篇综述旨在探讨可用于改变和增强抗菌活性的技术，抗菌谱和物理化学性质(溶解度，乳酸链球菌素的溶液稳定性和蛋白酶抗性)。基本上有两种获得乳链菌肽类似物的通用方法-蛋白质工程和该抗生素的化学官能化。尽管生物工程技术已经得到了很好的发展，并且能够创建具有可变结构和特性的乳酸链球菌素突变体，到目前为止，他们缺乏壮观的效果。基于利用其游离氨基和羧基部分的反应性，对乳酸链球菌素进行化学修饰。以及脱氢氨基酸双键的反应性，正处于婴儿期。
