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

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.

Arabidopsis sculpt distinct root-associated microbiomes through the synthesis of secondary metabolites and defense signaling molecules

“…The yeasts Sporobolomyces, which were enriched mostly in the FAD, dde2 and npr1-2 mutants, are abundant members of the plant mycobiome(50,51) and have been shown to have antagonistic effects against pathogens(52). Some members of Emericellopsis are known to possess biocontrol traits via the antimicrobial compound emericellipsin A, which have been shown to suppress the pathogen Aspergillus niger(53).Furthermore, the clear separation of GLS mutants from Col-0 observed on a PCoA plot further supports our findings. In particular, the bacterial communities were strongly affected in cyp79B3 and TU3 mutants.…”

Structural Diversity and Bioactivities of Peptaibol Compounds From the Longibrachiatum Clade of the Filamentous Fungal Genus Trichoderma

“…Furthermore, peptaibols (trichokonin VI) could inhibit HepG2 cancer cells by inducing autophagy and apoptosis through an influx of Ca 2+ , which triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and the subsequent promotion of apoptosis (Shi et al, 2010). Another peptaibol, emericellipsin A, which is a short lipopeptaibol, exhibited selective cytotoxic activity against HepG2 and HeLa cell lines (Rogozhin et al, 2018), similar to culicinin D, another short linear peptaibol which has been described as a potent anticancer compound (He et al, 2006). In the present study, the partially purified peptaibol extract of T .…”

A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

“…Bacterial cells in 50 µl were transferred to a 96-well microtiter plate (Eppendorf, Germany). Measurements of SYTO 9 fluorescence kinetics were performed on a Fluoroskan Ascent FL plate reader (Thermo Fisher Scientific, United States) at 485 nm excitation and 535 nm emission wavelengths as described earlier (Rogozhin et al, 2018). Assessment of the viability of bacterial cells was performed by the agar-drop plate assay using one part of the treated bacterial population.…”