Structural gene isolation and prepeptide sequence of gallidermin, a new lanthionine containing antibiotic

Abstract

Peptide antibiotics containing lanthionine and 3‐methyllanthionine bridges, named lantibiotics [1], are of increasing interest. A new lantibiotic, gallidermin, has been isolated from Staphylococcus gallinarum. Here we report the isolation of its structural gene which we name gdmA. In all lantibiotics so far studied genetically, three peptides can be formally distinguished: (i) the primary translation product, which we call the prepeptide; (ii) the propeptide lacking the leader sequence and (iii) the mature lantibiotic. Unlike the plasmid‐coded epidermin, gdmA is located on the chromosome. The gdmA locus codes for a 52 amino acid residue prepeptide, consisting of an α‐helical leader sequence of hydrophilic character, which is separated from the C‐terminus (propeptide) by a characteristic proteolytic processing site (Pro−2 Arg−1 Ile1). Although pro‐gallidermin

Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes

“…Confirmation of a ribosomal origin for lanthipeptides was firmly established in the late 1980s as sequences of several lantibiotic biosynthetic clusters revealed the presence of genes that encode for peptidic precursors of lanthipeptides, such as those for epidermin, 2 subtilin, 159 nisin, 160−162 and gallidermin. 163 Importantly, each of these gene sequences codes for peptides that contain an N-terminal leader sequence that is absent in the final products and a C-terminal core sequence that contains codons for Ser, Thr, and Cys at the sites of the post-translational modifications in the final products.…”

Staphylococcuscolonization of the skin and antimicrobial peptides

“…Some strains of S. epidermidis produce lantibiotics, such as epidermin, epilancins K7 and 15X, and Pep5, which have high bactericidal potency against many Gram-positive bacteria [56–60]. Other lantibiotics have been described in S. warneri [61,62], Staphylococcus gallinarum [63] and S. aureus [64]. Commonly, genes encoding bacteriocins are coupled to genes that provide producer protection, thus giving an at least hypothetical advantage over other bacteria that are susceptible to that substance [65].…”

Biosynthesis and biological activities of lantibiotics with unique post-translational modifications

“…Van der Meer et al (1994) showed that production of some nisin leader peptide variants was not possible, although the mutated genes were transcribed, unless the host contained an unchanged nisin gene. nisin A and Z as well as epidermin and gallidermin (Schnell et al, 1989) are not considered as different in this context. A similar effect was observed with mutated Pep5 where the exchange Phe23-Asp significantly reduced production yields (Bierbaum et al, 1994) and with the Pep5 immunity peptide which is not produced in the absence of intact pepA .…”