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Dilarmycins A-C, Calcium-Dependent Lipopeptide Antibiotics with a Non-canonical Ca2+-Binding Motif
Ignacio Fernández-Pastor1, Francisco Javier Ortiz-López1, Daniel Oves-Costales1
1Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía. Avenida del Conocimiento, 34, 18016 Armilla, Granada, Spain.
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.
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