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Dilarmycins A–C, Calcium-Dependent Lipopeptide Antibiotics with a Non-canonical Ca2+-Binding Motif

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posted on 2024-02-08, 15:40 authored by Ignacio Fernández-Pastor, Francisco Javier Ortiz-López, Daniel Oves-Costales, Jesús Martín, Pilar Sánchez, Ángeles Melguizo, Fernando Reyes, Tilmann Weber, Olga Genilloud
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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