Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms.

[11] Common adverse drug reactions associated with daptomycin therapy include:[4][12] Less common, but serious adverse events reported in the literature include Also, myopathy and rhabdomyolysis have been reported in patients simultaneously taking statins,[15] but whether this is due entirely to the statin or whether daptomycin potentiates this effect is unknown.

Due to the limited data available, the manufacturer recommends that statins be temporarily discontinued while the patient is receiving daptomycin therapy.

[citation needed] Daptomycin has a distinct mechanism of action, disrupting multiple aspects of bacterial cell membrane function.

A four-million year-old strain of Paenibacillus isolated from soil samples in Lechuguilla Cave was found to be naturally resistant to daptomycin.

[22] Data from in vitro and in vivo studies suggest that a tailored approach should be used taking into account both the causative agent and the site of infection.

[23] Daptomycin has been shown to be non-inferior to standard therapies (nafcillin, oxacillin, flucloxacillin or vancomycin) in the treatment of bacteraemia and right-sided endocarditis caused by S.

[25] In Phase III clinical trials, limited data showed daptomycin to be associated with poor outcomes in patients with left-sided endocarditis.

[citation needed] The NRPS responsible for the synthesis of daptomycin is encoded by three overlapping genes, dptA, dptBC and dptD.

The dptE and dptF genes, immediately upstream of dptA, are likely to be involved in the initiation of daptomycin biosynthesis by coupling decanoic acid to the N-terminal Trp.

[30] These novel genes (dptE, dptF ) correspond to products that most likely work in conjunction with a unique condensation domain to acylate the first amino acid (tryptophan).

The biosynthetic machinery of an NRPS system is composed of multimodular enzymatic assembly lines that contain one module for each amino acid monomer incorporated.

An adenylation domain selects the amino acid monomer to be incorporated and activates the carboxylate with ATP to make the aminoacyl-AMP.

[medical citation needed] The first five modules of the NRPS are encoded by the dptA gene and catalyze the condensation of L-tryptophan, D-asparagine, L-aspartate, L-threonine, and glycine, respectively (Figure 4).

[29] Elongation by these NRPS modules ultimately leads to macrocyclization and release in which an α-amino group, namely threonine, acts as an internal nucleophile during cyclization to yield the 10-amino-acid ring (Figure 6).

[31] The molecular engineering of daptomycin, the only marketed acidic lipopeptide antibiotic to date (Figure 8), has seen many advances since its inception into clinical medicine in 2003.

[38] Daptomycin, originally designated as LY 146032, was discovered by researchers at Eli Lilly and Company in the late 1980s from the actinomycete Streptomyces roseosporus.

LY 146032 showed promise in phase I/II clinical trials for treatment of infection caused by Gram-positive organisms.