However, in some cases, a single protein LanT is responsible to export the precursor peptide and cleavage of leader peptide simultaneously 8. Finally, cytoplasmic membrane protein LanT (an ATP-binding cassette transporter) exports the modified precursor peptide outside the cell and an extracellular protease LanP cleaves the leader peptide to release the active lantibiotic.
For class III and class IV lantibiotics, tridomain proteins LanKC and LanL catalyze the formation of lanthipeptides, respectively 1. However, in class II lantibiotics, a biofunctional enzyme LanM introduces Lan or MeLan rings. In the class I lantibiotics, a dedicated dehydratase LanB, and a cyclase LanC perform dehydration and cyclization 1. Recently, lantibiotics were classified in four classes based on the modification enzymes responsible for dehydration and cyclization 1.
Biosynthesis genes of lantibiotics are organized in the same gene clusters, which include the genes coding for the precursor peptides and other essential proteins involved in post-translational modification, processing of leader peptide, transportation, immunity, and regulation 6, 7. These thio-ether ring structures are assumed to provide the rigidity and impart resistance to proteolytic enzymes, temperature, pH and other parameters. During the posttranslational modification unusual amino acids like Lan and MeLan are formed through intermolecular cyclization of the thiol groups of cysteine residues with Dha and Dhb, which are the dehydrated products of specific serine and threonine residues, respectively 2.
This prepeptide sequentially undergoes several posttranslational modifications to become the mature lantibiotic. Producer strains synthesize lantibiotics as inactive prepeptides that consist of an N-terminal leader sequence and a C-terminal prepeptide part. A few Gram-negative bacteria were also found to produce lantibiotics reported in recent years 4, 5. These peptides are mostly produced by a variety of Gram-positive bacteria and usually show antagonizing activity against Gram-positive bacteria, especially closely related species 2, 3. Lantibiotics are ribosomally synthesized antimicrobial peptides possessing unusual amino acids normally not found in nature like lanthionine (Lan)- or methyllanthionine (MeLan) 1. Homicorcin exerts bactericidal activity against susceptible cells by disrupting the integrity of the cytoplasmic membrane through pore formation as observed under FE-SEM. Trypsin digestion of the core peptide and its variant followed by ESI–MS analysis suggests the presence of three ring structures, one in the N-terminal and other two interlocking rings at the C-terminal region that remain undigested. The presence of an oxidoreductase ( homO) similar to that of epicidin 280- associated eciO or epilancin 15X- associated elxO in the homicorcin gene cluster is predicted to be responsible for the reduction of the first dehydrated residue dehydroalanine (Dha) to 2-hydroxypropionate that causes an increase of 3 Da mass of homicorcin 1. Two distinct peaks obtained at close retention times from a RP-HPLC purified fraction have comparable antimicrobial activities and LC–MS revealed the molecular mass of these peaks to be 3046.2 Da. The predicted lantibiotic (homicorcin) was found to be 82% similar to a reported peptide epicidin 280 having a difference of seven amino acids at several positions of the core peptide.
The whole genome sequence of this strain, annotated using BAGEL4 and antiSMASH 5.0 to predict the gene clusters for antimicrobial substances identified a novel antimicrobial peptide cluster that belongs to the class I lantibiotic group. Here we report a jute endophyte Staphylococcus hominis strain MBL_AB63 isolated from jute seeds which showed promising antimicrobial activity against Staphylococcus aureus SG511 when screening for antimicrobial substances.