Daptomycin is a cyclic lipopeptide antibiotic produced by the organism Streptomyces roseosporus.4]5] Daptomycin consists of thirteen amino acids, ten of which are arranged in a cyclic fashion, and three that adorn an exocyclic tail. Two non-proteinogenic amino acids exist in the lipopeptide, the unusual amino acid L-kynurenine (Kyn), only known to Daptomycin, and L-3-methylglutamic acid (mGlu). The N-terminus of the exocyclic tryptophan residue is coupled to decanoic acid, a medium chain (C10) fatty acid. Biosynthesis is initiated by the coupling of decanoic acid to the N-terminal tryptophan, followed by the coupling of the remaining amino acids by nonribosomal peptide synthetase (NRPS) mechanisms. Finally, a cyclization event occurs, which is catalyzed by a thioesterase enzyme, and subsequent release of the lipopeptide is granted.
The non-ribosomal peptide synthetase (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.6] 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). These and other novel genes (dptI, dptJ) are believed to be involved in supplying the non-proteinogenic amino acids L-3-methylglutamic acid and Kyn; they are located next to the NRPS genes.6] From suzhou pharmaceutical