Daptomycin

Daptomycin is a unique lipopeptide antibiotic derived from Streptomyces roseosporus that is effective against Gram-positive bacteria. This holoenzyme is composed of three subunits, encoded by the dptA, dptBC, and dptD genes, each responsible for incorporating particular amino acids into the peptide. The cloned dpt gene cluster allows study of Daptomycin biosynthesis and discovery of novel lipopetides through pathway engineering. Daptomycin is soluble in water, DMSO, methanol, and ethanol.

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Background

Daptomycin peptides interact with anionic phospholipids in the membrane of Gram-positive bacteria. Peptides integrate into the membrane by a calcium-mediated process and interact with membrane phospholipid head groups and acyl chains. Finally, a pore or channel is formed which can kill the cell by membrane disruption/depolarization or cellular uptake of Daptomycin leading to disruption of intracellular processes such as synthesis of DNA, RNA, and protein which results in bacterial cell death. The activity of Daptomycin is dependent on the presence of physiologic levels of free calcium ions. Researchers found a gradual dissipation of membrane potential, thus membrane depolarization is an inherent part of its mechanism of action (Silverman et al, 2003).