Bacteriocin-like peptide modification system

A bacteriocin-like peptide modification system in prokaryotes is a set of genes that includes ribosomally translated polypeptides that are targets for post-translational modification, modification enzymes referred to as peptide maturases, and transporters to export the mature peptide from the cell.

Peptide maturases, a guild of protein families, include lanthionine synthetases (producing lantipeptides), cyclodehydrases (producing thiazole/oxazole-modified microcins (TOMMs), and certain branches of other protein families, including radical SAM/SPASM domain proteins and ATP-grasp proteins. New families of both maturases and precursor peptides are still being discovered.

A clear majority of lantipeptides appear to function as bacteriocins, that is, small peptide antibiotics, and so are referred to as lantibiotics. It is an error, however, to presume antimicrobial activity by default for products made by other classes of peptide maturases. A bacteriocin-like_peptide_modification_system may actually produce a pheromone, that is, a signaling molecule. The SCIFF system (Six Cys in Forty-Five residues), whose function is unknown, is so well conserved in the Clostridiales (better even than the capacity for endospore formation) that a housekeeping-type role seems likely.

Precursor peptide and peptide maturation genes usually are adjacent, although exceptions occur, such as the Cys-Xaa-Xaa repeat TOMM of Bacillus anthracis.Sequence gazing will often show a Gly-Gly residue pair, which is a common cleavage motif for bacteriocins, separating an N-terminal leader peptide that gets removed during processing from the C-terminal core peptide that gives rise to the eventual product. In multiple sequence alignments, the leader peptide will be relatively well-conserved, while the core peptide regions will be hypervariable, and often repetitive, with low-complexity sequence rich in Cys, Ser, Thr, and Gly.

A bacteriocin biosynthesis cassette may include an immunity protein, although there is no established technique for predicting novel families of immunity proteins. Bacteriocin biosynthesis cassettes often contain several homologous precursors, presumably to make a broader range of lethal peptides with the same set of maturases. They may show more sporadic distribution than pheromone systems - less conserved among closely related strains but more likely to resemble systems from taxonomically very distant species.

In some cases, namely PQQ and the proposed mycofactocin system, bacteriocin-like peptide modification system makes a cofactor, rather than an antibiotic, from a peptide precursor. These systems lack an export transporter, and instead show the bioinformatics grammar of a cofactor dependency signature.