期刊
CHEMBIOCHEM
卷 10, 期 4, 页码 607-616出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200800546
关键词
acidic lipopeptides; antibiotics; daptomycin; NRPS; peptides; tailoring enzymes
资金
- Deutsche Forschungsgemeinschaft
- Fonds der Chemischen Industrie
Acidic lipopeptide antibiotics are a new class of potent antibiotics, which Includes daptomycin, A54145, calcium-dependent antibiotics (CDAs), friulimicins/amphomycins, laspartomycin/glycinocins and others. The importance of this novel class is exemplified by the success story of the clinically approved daptomycin, which is used for the treatment of skin infections and bacteremia caused by multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The potency of acidic lipopeptides is inherent in their chemical structure. The nonribosomally synthesized peptide cores consist of eleven to 13 amino acids, which are rigidified by the formation of a ten-membered ring. An N-terminal fatty acid, which facilitates insertion into the lipid bilayer of bacterial membranes, completes the structure. All these antibiotics contain multiple nonproteinogenic amino acids as well as different lipid tails; this yields remarkable structural diversity. This review summarizes the observed structural variety through a detailed description of the composition of the acidic lipopeptides. Furthermore, engineering approaches towards novel lipopeptides are presented. Recent discoveries in the field of tailoring enzymes, which enable structural plurality mainly by amino and fatty acid precursor biosynthesis, are highlighted.
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