PUBLICATION

Emerimicins V-X, 15-Residue Peptaibols Discovered from an Acremonium sp. through Integrated Genomic and Chemical Approaches

Authors
Wu, G., Dentinger, B.T.M., Nielson, J.R., Peterson, R.T., Winter, J.M.
ID
ZDB-PUB-210223-12
Date
2021
Source
Journal of natural products   84(4): 1113-1126 (Journal)
Registered Authors
Peterson, Randall
Keywords
none
MeSH Terms
  • Acremonium/chemistry*
  • Animals
  • Anti-Bacterial Agents/isolation & purification
  • Anti-Bacterial Agents/pharmacology*
  • Embryo, Nonmammalian/drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Peptaibols/isolation & purification
  • Peptaibols/pharmacology*
  • Soil Microbiology
  • Toxicity Tests
  • Utah
  • Zebrafish/embryology
PubMed
33617244 Full text @ J. Nat. Prod.
Abstract
Fermentation of Acremonium tubakii W. Gams isolated from a soil sample collected from the University of Utah led to the isolation and characterization of six new linear pentadecapeptides, emerimicins V-X (1-6). Peptaibols containing 15-residues are quite rare, with only 22 reported. Genome mining and bioinformatic analysis were used to identify the emerimicin 60 kbp eme biosynthetic cluster harboring a single 16-module hybrid polyketide-nonribosomal peptide synthetase. A detailed bioinformatic investigation of the corresponding 15 adenylation domains, combined with 1D and 2D NMR experiments, LC-MS/MS data, and advanced Marfey's method, allowed for the elucidation and absolute configuration of all proteinogenic and nonproteinogenic amino acid residues in 1-6. As some peptaibols possess cytotoxic activity, a zebrafish embryotoxicity assay was used to evaluate the toxicity of the six emerimicins and showed that emerimicin V (1) and VI (2) exhibit the most potent activity. Additionally, out of the six emerimicins, 1 displayed modest activity against Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium with MIC values of 64, 32, and 64 μg/mL, respectively.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping