ACS Chem Biol. 2018 Oct 19;13(10):2966-2972. doi: 10.1021/acschembio.8b00599. Epub 2018 Sep 18.
Glycocins (glycosylated bacteriocins) are a family of ribosomally synthesized and post-translationally modified peptides with antimicrobial activities against pathogens of interest, including methicillin-resistant Staphylococcus aureus, representing a promising source of new antibiotics. Glycocins are still largely underexplored, and thus far, only six glycocins are known. Here, we used genome mining to identify 50 putative glycocin biosynthetic gene clusters and then chose six of them with distinct features for further investigation. Through two rounds of plug-and-play pathway refactoring and expression in Escherichia coli BL21(DE3), four systems produced novel glycocins. Further structural characterization revealed that one of them, which belongs to the enterocin 96-type glycocins, was diglucosylated on a single serine. The other three compounds belong to the SunA/ThuA-type glycocins and exhibit a antimicrobial spectrum narrower than that of sublancin, the best characterized member in this group, even though they share a similar disulfide topology and glycosylation. Further evaluation of their bioactivities with free glucose at high concentrations suggested that their antimicrobial mechanisms might be both glycocin- and species-specific. These glycocins with distinct features significantly broaden our knowledge and may lead to the discovery of new classes of antibiotics.
糖基化细菌素（glycosylated bacteriocins）是一类核糖体合成并经过翻译后修饰的肽类，具有抗目标病原体的抗菌活性，包括耐甲氧西林金黄色葡萄球菌，是一种很有前途的新型抗生素来源。糖基化细菌素在很大程度上仍未得到充分探索，迄今为止，仅已知六种糖基化细菌素。在这里，我们使用基因组挖掘来鉴定 50 个推定的糖基化细菌素生物合成基因簇，然后选择其中六个具有独特特征的基因簇进行进一步研究。通过两轮插装式途径重构和在大肠杆菌 BL21(DE3)中的表达，四个系统产生了新型糖基化细菌素。进一步的结构特征表明，其中一种属于肠球菌素 96 型糖基化细菌素，在单个丝氨酸上双糖基化。另外三种化合物属于 SunA/ThuA 型糖基化细菌素，其抗菌谱比该组中研究最充分的亚抑菌素更窄，尽管它们具有相似的二硫键拓扑结构和糖基化。进一步评估它们在高浓度游离葡萄糖存在下的生物活性表明，它们的抗菌机制可能既有糖基化细菌素特异性又有物种特异性。这些具有独特特征的糖基化细菌素极大地拓宽了我们的知识，并可能导致新类别的抗生素的发现。
