Lipopeptide antibiotic daptomycin

One of the most characteristic features of FRET is its sensitive dependency on the fluorophore distance. This is advantageously used to evaluate structures and conformational changes of peptides, glycopeptides, and proteins among other molecules [164-166], The conformational change of the lipopeptide antibiotic daptomycin from an inactive linear form to a biological active cyclic form... 

Baltz, R.H., Miao, V. and Wrigley, S.K. (2005) Natural products to drugs daptomycin and related lipopeptide antibiotics. Natural Product Reports, 22, 717. 

Coeffet-Le Gal, M.F., Thurston, L., Rich, P. et al. (2006) Complementation of daptomycin dpt A and dptD deletion mutations in trans and production of hybrid lipopeptide antibiotics. Microbiology (Reading, England), 152,2993. 

Grunewald, J., Sieber, S.A., Mahlert, C. et al. (2004) Synthesis and derivatization of daptomycin a chemoenzy-matic route to acidic lipopeptide antibiotics. Journal of the American Chemical Society, 126, 17025. 

A novel cyclic lipopeptide antibiotic was isolated from cultures of Strep-tomyces roseosporus grown in the presence of decanioc acid. Daptomycin interacts with the bacterial cell membrane and interferes with membrane potential.Unlike polymyxin B, daptomycin can target majority of clinically relevant Gram-positive pathogens. 

Daptomycin is a novel lipopeptide antibiotic, an inhibitor of lipoteichoic acid synthesis, with potent bactericidal activity against most clinically important Gram-positive bacteria, including resistant strains (1,2). 

Daptomycin was originally isolated from the soil saprotroph Streptomyces roseos-porus by scientists at Eli Lilly and Company in the 1980s. It is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. The proposed mechanism of action involves insertion of the lipophilic daptomycin tail into the bacterial cell membrane, causing rapid membrane depolarization and a potassium ion efflux. This leads to the arrest of DNA, RNA, and protein synthesis, resulting in bacterial cell death (see footnote 1). 

Woodworth JR, Nyhart EH, Brier GL, Wolny JD, Black HR. Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers. Antimicrob Agent Chemothet 1992 36 318-325. 

Sexton D, Brown R, McCloskey R, Dowell AR, Daptomycin Study Group. The use of dap-lomycin, a lipopeptide antibiotic, in the iieatment of gram positive infections in man. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy, 1988 A932. 

Even newer is the natural product daptomycin (Cubicin), a complex cyclic lipopeptide structure, approved for use in the United States in 2003. Daptomycin has a spectrum similar to that of linezolid and specifically includes MRSA and VRE. In contrast to linezolid, daptomycin is bactericidal for these Gram-positive organisms. It is, like vancomycin, a parenteral antibiotic and is given intravenously. It is indicated for treatment of complicated skin and skin structure infections and for some cases of bacteremia, including endocarditis. Daptomycin may be thought of as an alternative to vancomycin. 

Straus SK, Hancock RE. (2006) Mode of action of the new antibiotic for Gram-positive pathogens daptomycin Comparison with cationic antimicrobial peptides and lipopeptides. Biochim BiophysActa 1758 1215-1223. 

Like many other peptide antibiotics—including the lipopeptides A54145, CDA, amphomycin, laspartomycin and friulimicin daptomycin is produced by a nonribosomal peptide synthetase (NRPS) mechanism.3,6,14 It is produced in fermentation by S. roseosporus by feeding decanoic acid, which is incorporated as the fatty acid starter unit. Much has been learned about the biosynthetic process by fermentation feeding studies and by the analysis of the daptomycin biosynthetic genes.3,6,14,15... 

Daptomycin (CUBICIN) is a cyclic lipopeptide that was resurrected in response to increasing need for bactericidal antibiotics effective against vancomycin-resistant gram-positive bacteria... 

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