Heterologous Expression and Characterization of Estercin A, a Class II Lanthipeptide Derived from Clostridium estertheticum CF016, with Antimicrobial Activity against Clinically Relevant Pathogens.

Abstract

Recent genome mining work revealed that unexplored habitats exhibit great potential for discovering new nonribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides are a group of RiPPs exhibiting a variety of biological functions. They are characterized by the presence of the thioether-containing bis-amino acids lanthionine and/or methyllanthionine. In this study, we heterologously expressed and structurally characterized estercin A, an unprecedented class II lanthipeptide derived from Clostridium estertheticum CF016 in Escherichia coli. Comprising 27 amino acids, estercin A features three overlapping (methyl-)lanthionine rings, with a shorter C-terminal part compared to most reported class II lanthipeptides. Estercin A exhibited selective antimicrobial properties against methicillin-resistant Staphylococcus aureus, bowel infection-associated Clostridium perfringens and Clostridium tetani. The mode of action of estercin A was determined as binding to lipid II on the cell membrane. Estercin A exhibited stability across a range of pH values and temperatures and showed resistance to degradation by trypsin. Our findings highlight estercin A as a novel and stable antimicrobial peptide with significant potential in combating clinically relevant pathogens.