Unveiling the biosynthesis mechanism of novel lantibiotic homicorcin: an in silico analysis

Jute endophyte Staphylococcus hominis strain MBL_AB63 was reported to produce a novel antimicrobial peptide, 'homicorcin'. This exhibits potential activity against a broad spectrum of Gram-positive bacteria. Eight genes were predicted to be involved in the sequential maturation of this peptide antibiotic, which includes structural (homA), dehydratase (homB), cyclase (homC), peptidase (homP), immunity (homI), oxidoreductase (homO), ATP-binding cassette transporter (homT1), and permease (homT2), respectively. Among the modification enzymes, HomB, HomC, and HomP exhibit sequence similarities with class I lantibiotic dehydratase, cyclase, and leader peptidase, respectively. The current study investigated the sequential modifications and secretion of homicorcin by constructing robust computational protein models and analyzing their interaction patterns using protein-protein docking techniques. To enhance comprehension of the protein arrangement, their subcellular localization was also extrapolated. The findings demonstrate a network of proteins that works in a synchronized manner, where HomC functions as an intermediary between HomB and the transporter (HomT). Following its dehydration by HomB and cyclization by HomC, the pro-homicorcin is taken out of the cell by the transporter and processed by HomP, resulting in the production of matured, processed homicorcin. This biosynthesis model for homicorcin will lay the groundwork for the sustainable and efficient production of this peptide antibiotic.