THE BIOSYNTHESIS OF THE LANTIBIOTICS EPIDERMIN, GALLIDERMIN, PEP5 ANDEPILANCIN K7

Lantibiotics are antibiotic peptides that contain the rare thioether a mino acids lanthionine and/or methyllanthionine. Epidermin, Pep5 and e pilancin K7 are produced by Staphylococcus epidermidis whereas gallide rmin (6L-epidermin) was isolated from the closely related species Stap hylococcus gallinarum. The biosynthesis of all four lantibiotics proce eds from structural genes which code for prepeptides that are enzymati cally modified to give the mature peptides. The genes involved in bios ynthesis, processing, export etc. are found in gene clusters adjacent to the structural genes and code for transporters, immunity functions, regulatory proteins and the modification enzymes LanB, LanC and LanD, which catalyze the biosynthesis of the rare amino acids. LanB and Lan C are responsible for the dehydration of the serine and threonine resi dues to give dehydroalanine and dehydrobutyrine and subsequent additio n of cysteine SH-groups to the dehydro amino acids which results in th e thioether rings. EpiD, the only LanD enzyme known so far, catalyzes the oxidative decarboxylation of the C-terminal cysteine of epidermin which gives the C-terminal S-aminovinylcysteine after addition of a de hydroalanine residue.