The daptomycin molecule in 3-D

The daptomycin molecule - rotatable in 3 dimensions

Daptomycin is a lipopeptide antibiotic, produced by Streptomyces roseosporus. It shows activity against most Gram-positive pathogens, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus (MRSA). Under the trade name Cubicin it was approved in 2003 by US-FDA for use against complicated skin and skin structure infections (cSSSI).

Molecular structure

Daptomycin consists of a chain of 13 amino acid residues, the last 10 forming a loop. Several are unusual (non-proteinogenic) amino acids and some are D-forms; its production involves nonribosomal peptide synthetase (NRPS) mechanisms. There is a carboxylic acid chain of 10 carbon atoms attached to the N-terminal end.
Name amino acids These labels appear next to the alpha-C atoms so the R-group extends away to one side;
Click on the individual links below to highlight each individually.

Lipo section
Decanoic acid chain
Peptide section - amino acid residues
TRP .. DSG .. ASP .. THR .. GLY .. ORN .. ASP .. DAL .. ASP .. GLY .. DSN .. LME .. KYN - linking back to THR by an ester bond, forming a lactone
Show double bonds

Label/ Unlabel atoms

Mode of action

It appears that under the influence of calcium ions, daptomycin inserts its lipophilic tail into the bacterial cell membrane, followed by aggregation into groups (oligomerisation) with a rosette shape, the centre of which forms a pore through which (potassium) ions leak out, resulting in membrane depolarisation and disruption of bacterial nucleic acid and protein metabolism, leading to cell death.

Resistant strains may produce enzymes to break off the lipoidal chain or open the ester bond, resulting in a change in the shape of the molecule.

Daptomycin cannot be used for lung infections as it binds to pulmonary surfactant.

Web references

Daptomycin From Wikipedia, the free encyclopedia

Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections Judith N. Steenbergen, Jeff Alder, Grace M. Thorne and Francis P. Tally

NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin Lee-Jon Ball, Catherine M. Goulta James A. Donarski, Jason Micklefield and Vasudevan Ramesh

Oligomerization of daptomycin on membranes Muraih JK1, Pearson A, Silverman J, Palmer M.

Inactivation of the Lipopeptide Antibiotic Daptomycin by Hydrolytic Mechanisms Vanessa M. D'Costaa, Tariq A. Mukhtara, Tejal Patela, Kalinka Kotevaa, Nicholas Waglechnera, Donald W. Hughesb, Gerard D. Wright and Gianfranco De Pascalea