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Copsin, a novel peptide-based fungal antibiotic interfering with the peptidoglycan synthesis

Andreas Essig1, Daniela Hofmann2, Daniela Münch3

  • 1From the Institute of Microbiology and.

The Journal of Biological Chemistry
|October 25, 2014
PubMed

Insights

Researchers discovered copsin, a novel antimicrobial peptide from the fungus Coprinopsis cinerea. This highly stable peptide targets bacterial cell wall synthesis, showing potential as a new antibiotic scaffold.

Area of Science:

  • Microbiology
  • Biochemistry
  • Structural Biology

Background:

  • Fungi and bacteria produce secreted molecules for ecological competition, serving as sources for antimicrobials.
  • Antimicrobial peptides (AMPs) are emerging fungal defense molecules with pharmaceutical potential.

Purpose of the Study:

  • To investigate the interaction between the basidiomycete Coprinopsis cinerea and bacteria.
  • To identify and characterize novel antimicrobial compounds produced by C. cinerea.

Main Methods:

  • Co-cultivation of C. cinerea with bacteria.
  • Recombinant production of the identified peptide (copsin) in Pichia pastoris.
  • NMR spectroscopy for three-dimensional structure determination.
  • Antibacterial assays against Gram-positive bacteria.
  • Mechanism of action studies, including binding to lipid II.

Main Results:

  • Identification of a novel defensin, copsin, from C. cinerea.
  • Copsin exhibits high stability due to its cysteine-stabilized α/β-fold, unique disulfide connectivity, and N-terminal pyroglutamate.
  • Copsin demonstrates bactericidal activity against Gram-positive bacteria, including pathogens like Enterococcus faecium and Listeria monocytogenes.
  • Copsin binds to lipid II, inhibiting bacterial cell wall biosynthesis.
  • Effective binding requires interaction at the third position of the lipid II pentapeptide, distinct from other defensins and lantibiotics.

Conclusions:

  • Copsin is a novel, highly stable antimicrobial peptide with a unique mechanism of action.
  • Its specific interaction with lipid II suggests potential for developing new antibiotics targeting cell wall biosynthesis.
  • The structural features of copsin provide a promising scaffold for novel antimicrobial drug development.
Keywords:
Antibiotic ResistanceAntibioticsAntimicrobial Peptide (AMP)Bacterial-Fungal Interaction (BFI)Fungal SecretomeFungiLipid II

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