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Multiple Activities in Lantibiotics - Models for the Design of Novel Antibiotics?

Author(s): Ulrike Pag and Hans-Georg Sahl

Affiliation: Institute for MedicalMicrobiologie, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany

Keywords: Lantibiotics, lanthionine, methyllanthionine, aminoviny cysteine, aminoviny methyl cysteine, didelhydroalanine, didehyrobutyrine, lysinoalanine

Abstract:

Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and / or methyllanthionine. They are produced by Grampositive bacteria as gene-encoded precursor peptides and undergo post-translational modification to generate the mature peptide. The structural gene for the prepeptide and the genes involved in biosynthesis, processing, export as well as regulation and producer strain self-protection are organized in clusters. Based on their structural and functional features lantibiotics are currently divided into two major groups. The flexible amphiphilic type-A lantibiotics act primarily by pore formation in the bacterial membrane, a mechanism which was recently shown, e.g. for nisin and epidermin, to involve the interaction with specific docking molecules such as the membrane precursor lipid II. The rather rigid and globular type-B lantibiotics inhibit enzyme functions through interaction with the respective substrates: mersacidin and actagardine inhibit the cell wall biosynthesis by complexing lipid II, whereas the cinnamycin-like peptides inhibit phospholipases by binding phosphoethanolamine. Lantibiotics have attracted much attention in recent years and undergone extensive characterization. New insights into the mode of action and structure-function relationships as well as the biochemistry and the genetics will be outlined in this review.

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Article Details

VOLUME: 8
ISSUE: 9
Page: [815 - 833]
Pages: 19
DOI: 10.2174/1381612023395439