Multiple activities in lantibiotics - Models for the design of novel antibiotics?

被引:109
作者
Pag, U [1 ]
Sahl, HG [1 ]
机构
[1] Inst Med Microbiol, D-53105 Bonn, Germany
关键词
D O I
10.2174/1381612023395439
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and/or methyllanthionine. They are produced by Gram-positive 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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页码:815 / 833
页数:19
相关论文
共 195 条
[1]   EPIDERMIN - SEQUENCING OF A HETERODET TETRACYCLIC 21-PEPTIDE AMIDE ANTIBIOTIC [J].
ALLGAIER, H ;
JUNG, G ;
WERNER, RG ;
SCHNEIDER, U ;
ZAHNER, H .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1986, 160 (01) :9-22
[2]   Biosynthesis of the lantibiotic mersacidin: Organization of a type B lantibiotic gene cluster [J].
Altena, K ;
Guder, A ;
Cramer, C ;
Bierbaum, G .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2000, 66 (06) :2565-2571
[3]   Type II topoisomerases as targets for quinolone antibacterials: turning Dr. Jekyll into Mr. Hyde [J].
Anderson, VE ;
Osheroff, N .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (05) :337-353
[4]   GENETIC-ANALYSIS OF EPIDERMIN BIOSYNTHETIC GENES AND EPIDERMIN-NEGATIVE MUTANTS OF STAPHYLOCOCCUS-EPIDERMIDIS [J].
AUGUSTIN, J ;
ROSENSTEIN, R ;
WIELAND, B ;
SCHNEIDER, U ;
SCHNELL, N ;
ENGELKE, G ;
ENTIAN, KD ;
GOTZ, F .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 204 (03) :1149-1154
[5]   Pharmacology of phosphoinositides, regulators of multiple cellular functions [J].
Balla, T .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (06) :475-507
[6]  
Beck-Sickinger A. G., 1991, NISIN NOVEL LANTIBIO, P218
[7]  
Benz R, 1991, NISIN NOVEL LANTIBIO, P359
[8]   PURIFICATION AND NATURE OF THE ANTIBIOTIC NISIN [J].
BERRIDGE, NJ ;
NEWTON, GGF ;
ABRAHAM, EP .
BIOCHEMICAL JOURNAL, 1952, 52 (05) :529-535
[9]   CONSTRUCTION OF AN EXPRESSION SYSTEM FOR ENGINEERING OF THE LANTIBIOTIC PEP5 [J].
BIERBAUM, G ;
REIS, M ;
SZEKAT, C ;
SAHL, HG .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 1994, 60 (12) :4332-4338
[10]   AUTOLYTIC SYSTEM OF STAPHYLOCOCCUS-SIMULANS-22 - INFLUENCE OF CATIONIC PEPTIDES ON ACTIVITY OF N-ACETYLMURAMOYL-L-ALANINE AMIDASE [J].
BIERBAUM, G ;
SAHL, HG .
JOURNAL OF BACTERIOLOGY, 1987, 169 (12) :5452-5458