COMPARISON OF LANTIBIOTIC GENE CLUSTERS AND ENCODED PROTEINS

Lantibiotics form a group of modified peptides with unique structures, containing post-translationally modified amino acids such as dehydrat ed and lanthionine residues. In the gram-positive bacteria that secret e these lantibiotics, the gene clusters flanking the structural genes for various linear (type A) lantibiotics have recently been characteri zed. The best studied representatives are those of nisin (nis), subtil in (spa), epidermin (epi), Pep5 (pep), cytolysin (cyl), lactocin S (la s) and lacticin 481 (lct). Comparison of the lantibiotic gene clusters shows that they contain conserved genes that probably encode similar functions. The nis, spa, epi and pep clusters contain lanB and lanC ge nes that are presumed to code for two types of enzymes that have been implicated in the modification reactions characteristic of all lantibi otics, i.e. dehydration and thio-ether ring formation. The cyl, las an d let gene clusters have no homologue of the lanB gene, but they do co ntain a much larger lanM gene that is the lanC gene homologue. Most la ntibiotic gene clusters contain a lanP gene encoding a serine protease that is presumably involved in the proteolytic processing of the prel antibiotics. All clusters contain a lanT gene encoding an ABC transpor ter likely to be involved in the export of (precursors of) the lantibi otics. The lanE, lanF and lanG genes in the nis, spa and epi clusters encode another transport system that is possibly involved in self-prot ection. In the nisin and subtilin gene clusters two tandem genes, lanR and lanK, have been located that code for a two-component regulatory system. Finally, non-homologous genes are found in some lantibiotic ge ne clusters. The nisI and spaI genes encode lipoproteins that are invo lved in immunity, the pepI gene encodes a membrane-located immunity pr otein, and epiD encodes an enzyme involved in a post-translational mod ification found only in the C-terminus of epidermin. Several genes of unknown function are also found in the las gene cluster. A database ha s been assembled for all putative gene products of type A lantibiotic gene clusters. Database searches, multiple sequence alignment and seco ndary structure prediction have been used to identify conserved sequen ce segments in the LanB, LanC, LanE, LanF, LanG, LanK, LanM, LanP, Lan R and LanT gene products that may be essential for structure and funct ion. This database allows for a rapid screening of newly determined se quences in lantibiotic gene clusters.