Discovery of the Class I Antimicrobial Lasso Peptide Arcumycin.

Journal Article (Journal Article)

Lasso peptides are a structurally diverse superfamily of conformationally constrained peptide natural products, of which a subset exhibits broad antimicrobial activity. Although advances in bioinformatics have increased our knowledge of strains harboring the biosynthetic machinery for lasso peptide production, relating peptide sequence to bioactivity remains a continuous challenge. To this end, genome mining investigation of Actinobacteria-produced antimicrobial lasso peptides was performed to correlate predicted structure with antibiotic activity. Bioinformatic evaluation revealed eight putative novel class I lasso peptide sequences. Fermentation of one of these hits, Streptomyces NRRL F-5639, resulted in the production of a novel class I lasso peptide, arcumycin. Arcumycin exhibited antibiotic activity against Gram-positive bacteria including Bacillus subtilis (4 μg/mL), Staphylococcus aureus (8 μg/mL), and Micrococcus luteus (8 μg/mL). Arcumycin treatment of B. subtilis liaI-β-gal promoter fusion reporter strain resulted in upregulation of the liaRS system by the promoter liaI, indicating arcumycin interferes with lipid II biosynthesis. Cumulatively, the results illustrate the relationship between phylogenetically related lasso peptides and their bioactivity as validated through the isolation, structural determination, and evaluation of bioactivity of the novel class I antimicrobial lasso peptide arcumycin.

Full Text

Duke Authors

Cited Authors

  • Stariha, LM; McCafferty, DG

Published Date

  • August 2021

Published In

Volume / Issue

  • 22 / 16

Start / End Page

  • 2632 - 2640

PubMed ID

  • 34133845

Electronic International Standard Serial Number (EISSN)

  • 1439-7633

International Standard Serial Number (ISSN)

  • 1439-4227

Digital Object Identifier (DOI)

  • 10.1002/cbic.202100132

Language

  • eng