Article,
Dilarmycins A–C, Calcium-Dependent Lipopeptide Antibiotics with a Non-canonical Ca2+-Binding Motif
Affiliations
- [1] Fundación Medina [NORA names: Spain; Europe, EU; OECD];
- [2] Technical University of Denmark [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD]
Abstract
Genome analysis of strain Streptomyces sp. CA-278952 revealed a biosynthetic gene cluster encoding a putative lipopeptide with a sequence containing an Asp-Gly-Glu-Ala motif. We envisioned that this motif could mimic the canonical Asp-X-Asp-Gly sequence found in previously reported calcium-dependent lipopeptide antibiotics. Chemical investigation of the producing strain led to the discovery of three novel lipodepsipeptides, dilarmycins A-C. The calcium-dependent antibacterial activity of the new compounds was confirmed against the Gram-positive pathogens methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.
Keywords
A-C.,
Asp-Gly-Glu-Ala,
Ca2+-binding motif,
a-C,
activity,
antibacterial activity,
antibiotics,
binding motif,
biosynthetic gene cluster,
calcium-dependent lipopeptide antibiotics,
chemical,
chemical investigation,
clusters,
compounds,
discovery,
gene cluster,
genome,
genomic analysis,
investigation,
lipodepsipeptides,
lipopeptide antibiotic,
lipopeptides,
methicillin-resistant <i>Staphylococcus aureus</i> (MR,
motif,
sequence,
strain,
vancomycin-resistant <i>En