1887

Abstract

Daptomycin is a lipopeptide antibiotic produced by and recently commercialized as Cubicin® (daptomycin-for-injection) for treatment of skin and skin-structure infections caused by Gram-positive pathogens. Daptomycin is synthesized by a non-ribosomal peptide synthetase (NRPS) encoded by three overlapping genes, , and . The and genes, immediately upstream of , are likely to be involved in the initiation of daptomycin biosynthesis by coupling decanoic acid to the N-terminal Trp. Analysis of RT-PCR data suggests that , , , , and possibly other genes are transcribed as one large message; however, it has been demonstrated that sequential translation of these genes from a long transcript is not essential for robust daptomycin production. The and the genes were deleted from the gene cluster, and expressed from ectopic positions in the chromosome under the control of the strong constitutive promoter to produce high levels of lipopeptides. This three-locus -complementation system was used to produce hybrid lipopeptide antibiotics by introducing the heterologous and genes from and , respectively, to complement the Δ mutation.

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2006-10-01
2019-11-14
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