A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus Emericellopsis alkalina

Molecules. 2018 Oct 27;23(11):2785. doi: 10.3390/molecules23112785.

Abstract

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

Keywords: 2D structure; Emericellopsis alkalina; Peptaibol; antibacterial activity; antifungal activity; cytotoxic properties; emericellipsin A.

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / isolation & purification
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Ascomycota / chemistry*
  • Ascomycota / metabolism
  • Bacteria / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Fungi / drug effects
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Molecular Structure

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents