Prokaryotic Antimicrobial Peptides From Genes to Applications
The book provides an overview of the advancement of fundamental knowledge and applications of antimicrobial peptides in biomedical, agricultural, veterinary, food, and cosmetic products. Antimicrobial peptides stand as potentially great alternatives to cu
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Genetics, Biosynthesis, Structure, and Mode of Action of Lantibiotics Anneke Kuipers, Rick Rink, and Gert N. Moll
Abstract Lantibiotics are lanthionine-containing peptide antibiotics. They are characterized by having meso-lanthionine(s) and/or b-methyllanthionine(s) or both. These intramolecular monosulfide cross-links render the peptide resistant against breakdown by peptidases. Moreover, in several cases, the (methyl)lanthionines are essential for interaction with the so-called docking molecule lipid II. The best known lantibiotic, nisin, highly effectively inhibits growth of target cells via two mechanisms: (1) abduction of the cell wall precursor lipid II from the septum and (2) formation of pores composed of lipid II and nisin. (Methyl)lanthionines result from two enzyme-catalyzed posttranslational modifications: dehydration of serines/threonines and coupling of the resulting dehydro amino acids to cysteines. Besides the localization of the thioether bridges and dehydro amino acids in the lantibiotics, also the three-dimensional structure of some lantibiotics has been resolved by NMR. Genes encoding proteins involved in the biosynthesis of lantibiotics are present in clusters and may comprise combinations of the following genes in varying order: a structural gene that encodes a leader peptide and the lantibiotic propeptide, modification enzyme(s), a transporter responsible for the export of the lantibiotic and in some cases for cleavage of the leader peptide, a leader peptidase, a so-called immunity protein involved in self-protection of the host cell, components of a transporter also involved in self-protection, and two components of an autoinduction system.
Introduction The name lantibiotics was introduced more than two decades ago (Schnell et al. 1988). Lantibiotics are ribosomally produced dehydroresidue- and (methyl)lanthioninecontaining peptides (Fig. 9.1). Lanthionines are thioether-bridged amino acids G.N. Moll (*) BiOMaDe Technology Foundation, Nijenborgh 4, 9747 Groningen, The Netherlands e-mail: [email protected]
D. Drider and S. Rebuffat (eds.), Prokaryotic Antimicrobial Peptides: From Genes to Applications, DOI 10.1007/978-1-4419-7692-5_9, © Springer Science+Business Media, LLC 2011
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Fig. 9.1 Examples of lantibiotics. (a) nisin, (b) mersacidin, (c) duramycin, (d) sapB and (e) labyrinthopeptin A2. (Methyl)lanthionines and lysinoalanine in black are conserved within structural groups termed A, B, and C distinguished by Rink et al. (2005). The vertical dotted line indicates local structural symmetry in this morphogenetic lantibiotic (D). “Lab” in Figure E is labionine
(Fig. 9.2a). They are predominantly produced by Gram-positive bacteria, and those with antib
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