| Autor: |
Wu G; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States., Dentinger BTM; Natural History Museum of Utah & School of Biological Sciences, University of Utah, Salt Lake City, Utah 84108, United States., Nielson JR; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Peterson RT; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Winter JM; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of natural products [J Nat Prod] 2021 Apr 23; Vol. 84 (4), pp. 1113-1126. Date of Electronic Publication: 2021 Feb 22. |
| DOI: |
10.1021/acs.jnatprod.0c01186 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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