Don’t RiPP Into the Sactipeptides!

Abstract

The sactipeptides are a group of ribosomally synthesized posttranslationally modified peptides (RiPPs) that display antimicrobial activity. Sactipeptides which exhibit antimicrobial activity are termed sactibiotics. The sactibiotics are a group of posttranslationally modified bacteriocins that are relatively poorly-studied group, especially in comparison to the extensively-studied lantibiotic subgroup of bacteriocins. The term sactipeptide/sactibiotic is designated to this group of RiPPs due to the presence of characteristic sulfur to α-carbon bridges. Sactipeptides which have been studied experimentally thus far include subtilosin A, thuricin CD, thurincin H, sporulation killing factor (SKF) and, most recently, hyicin 4244. Some of these sactibiotics have shown potent activity against pathogens, most notably thuricin CD against Clostridium difficile and subtilosin A against Gardnerella vaginalis and Listeria monocytogenes. In addition, subtilosin A and hyicin 4244 have also shown promising activity against biofilms of G. vaginalis and Staphylococcus species, respectively. More recent studies have provided insights into the mode of action of the sactibiotics thuricin CD and subtilosin A, whilst other studies have described advances in techniques utilized to elucidate the 3D structure of some of these sactipeptides. In this article, we outline some of these studies concerning the antimicrobial activity of known sactipeptides, their modes of action, structure and information about their genetic organization. Furthermore, we describe some genome mining studies which have been conducted in recent years with a view to discovering novel sactipeptides using an in silico approach.