Heterologous Expression and Characterization of Estercin A, a Class II Lanthipeptide Derived from Clostridium...

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.