CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Academy of Scientific and Innovation Research (AcSIR), Sector 19, Kamla Nehru Nagar, Ghaziabad 201002, India.
Glycobiology. 2021 Feb 9;31(2):89-102. doi: 10.1093/glycob/cwaa061.
Glycocins are the ribosomally synthesized glycosylated bacteriocins discovered and characterized in Firmicutes, only. These peptides have antimicrobial activity against several pathogenic bacteria, including Streptococcus pyogenes , methicillin-resistant Staphylococcus aureus and food-spoilage bacteria Listeria monocytogenes. Glycocins exhibit immunostimulatory properties and make a promising source of new antibiotics and food preservatives akin to Nisin. Biochemical studies of Sublancin, Glycocin F, Pallidocin and ASM1 prove that the nested disulfide-bonds are essential for their bioactivities. Using in silico approach of genome mining coupled with manual curation, here we identify 220 new putative glycocin biosynthesis gene clusters (PGBCs) spread across 153 bacterial species belonging to seven different bacterial phyla. Based on gene composition, we have grouped these PGBCs into five distinct conserved cluster Types I-V. All experimentally identified glycocins belong to Type I PGBCs. From protein sequence based phylograms, tanglegrams, global similarity heat-maps and cumulative mutual information analysis, it appears that glycocins may have originated from closely related bacteriocins, whereas recruitment of cognate glycosyltransferases (GTs) might be an independent event. Analysis further suggests that GTs may have coevolved with glycocins in cluster-specific manner to define distinctive donor specificities of GTs or to contribute to glycocin diversity across these clusters. We further identify 162 hitherto unreported PGBCs wherein the corresponding product glycocins have three or less than three cysteines. Secondary structure predictions suggest that these putative glycocins may not form di-nested disulfide-bonds. Therefore, production of such glycocins in heterologous host Escherichia coli is feasible and may provide novel antimicrobial spectrum and or mechanism of action for varied applications.
糖肽是在厚壁菌门中发现和鉴定的核糖体合成的糖基化细菌素。这些肽对多种致病菌具有抗菌活性，包括化脓性链球菌、耐甲氧西林金黄色葡萄球菌和食源性腐败菌单增李斯特菌。糖肽具有免疫刺激特性，是类似于乳链菌肽的新型抗生素和食品防腐剂的有前途的来源。Subalanin、Glycocin F、Pallidocin 和 ASM1 的生化研究证明，嵌套的二硫键对于它们的生物活性是必不可少的。通过基因组挖掘的计算方法与人工编辑相结合，我们在这里鉴定了 220 个新的假定糖肽生物合成基因簇 (PGBC)，分布在属于七个不同细菌门的 153 种细菌中。根据基因组成，我们将这些 PGBC 分为五个不同的保守簇类型 I-V。所有实验鉴定的糖肽都属于 I 型 PGBC。基于蛋白质序列的系统发育树、缠结图、全局相似性热图和累积互信息分析表明，糖肽可能起源于密切相关的细菌素，而同源糖基转移酶 (GT) 的募集可能是一个独立的事件。分析进一步表明，GT 可能以簇特异性的方式与糖肽共同进化，以定义 GT 的独特供体特异性，或为这些簇中的糖肽多样性做出贡献。我们进一步鉴定了 162 个迄今未报道的 PGBC，其中相应的产物糖肽有三个或少于三个半胱氨酸。二级结构预测表明，这些假定的糖肽可能不形成二嵌套二硫键。因此，在异源宿主大肠杆菌中生产这些糖肽是可行的，并且可能为各种应用提供新的抗菌谱和/或作用机制。
