Leaderless RiPPs expand the repertoire of fungal secondary metabolites

Sung Chul Park1, Livia D S Oster2, Jacob Golan3

  • 1Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706.

Insights

Scientists discovered a new class of leaderless fungal peptides in Amanita mushrooms. These novel peptides are highly expressed in invasive populations, potentially explaining the mushroom

Area of Science:

  • Biochemistry and Molecular Biology
  • Mycology
  • Bioinformatics

Background:

  • Ribosomally synthesized and post-translationally modified peptides (RiPPs) are diverse secondary metabolites found across kingdoms.
  • Fungal RiPP precursors typically contain a leader sequence essential for maturation, as exemplified by MSDIN peptides in toxic Amanita mushrooms.

Purpose of the Study:

  • To investigate novel RiPP subclasses in fungi, challenging the canonical understanding of fungal RiPP precursor structures.
  • To identify and characterize leaderless RiPPs in the deadly mushroom Amanita phalloides.

Main Methods:

  • Utilized a combination of Nuclear Magnetic Resonance (NMR) and tandem Mass Spectrometry (MS/MS) for structural analysis.
  • Employed an updated bioinformatic pipeline to associate specific MSDIN genes with identified leaderless peptides.
  • Quantified transcript expression levels of leaderless versus canonical MSDIN genes.

Main Results:

  • Discovered a novel subclass of leaderless RiPPs in Amanita phalloides, representing the first empirical example in fungi.
  • Established a direct link between specific MSDIN genes and these leaderless peptides.
  • Observed significantly higher transcript expression for leaderless MSDINs compared to canonical ones, particularly in invasive populations.

Conclusions:

  • Redefined the structural diversity of fungal RiPPs by introducing the concept of leaderless RiPPs.
  • The differential regulation and high expression of non-canonical RiPPs may play a crucial role in the invasion biology of Amanita phalloides.

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