Article, 2024

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

Organic Letters, ISSN 1523-7060, 1523-7052, Volume 26, 7, Pages 1343-1347, 10.1021/acs.orglett.3c04195

Contributors

Fernandez-Pastor, Ignacio 0000-0003-1729-0860 [1] Ortiz-López, Francisco Javier 0000-0002-9410-3718 (Corresponding author) [1] Oves-Costales, Daniel 0000-0001-9986-4623 (Corresponding author) [1] Martín, Jesús 0000-0001-7487-2790 [1] Sánchez, Pilar [1] Melguizo, Ángeles [1] Reyes, Fernando 0000-0003-1607-5106 [1] Weber, Tilmann 0000-0002-8260-5120 [2] Genilloud, Olga 0000-0002-4202-1219 [1]

Affiliations

  1. [1] Fundación Medina
  2. [NORA names: Spain; Europe, EU; OECD];
  3. [2] Technical University of Denmark
  4. [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

Funders

  • Novo Nordisk Foundation

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