ArticleThe Journal of biological chemistry2009
Processing of the phalloidin proprotein by prolyl oligopeptidase from the mushroom Conocybe albipes.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Myxarylin: TotalJournal of the American Chemical Society · 2026Article
- Molecular Phylogeny and Morphology Reveal Four New Species ofJournal of fungi (Basel, Switzerland) · 2025Article
- Zonation of the Vitis vinifera microbiome in Vino Nobile di Montepulciano PDO production area.Communications biology · 2024Article
- Exploring fungal RiPPs from the perspective of chemical ecology.Fungal biology and biotechnology · 2022Review
- Genome of lethal Lepiota venenata and insights into the evolution of toxin-biosynthetic genes.BMC genomics · 2019Article
- Two new species of Amanitasect.Phalloideae from Africa, one of which is devoid of amatoxins and phallotoxins.MycoKeys · 2019Article
- The MSDIN family in amanitin-producing mushrooms and evolution of the prolyl oligopeptidase genes.IMA fungus · 2018Article
- Biosynthetic Proteases That Catalyze the Macrocyclization of Ribosomally Synthesized Linear Peptides.Biochemistry · 2018Review
- Expansion and diversification of the MSDIN family of cyclic peptide genes in the poisonous agarics Amanita phalloides and A. bisporigera.BMC genomics · 2016Article
- Mechanisms of cyanobactin biosynthesis.Current opinion in chemical biology · 2016Review
- Production of (15)N-labeled α-amanitin in Galerina marginata.Toxicon : official journal of the International Society on Toxinology · 2015Article
- Peptide macrocyclization catalyzed by a prolyl oligopeptidase involved in α-amanitin biosynthesis.Chemistry & biology · 2014Article
- The chemistry and biology of theta defensins.Angewandte Chemie (International ed. in English) · 2014Review
- Prospecting genomes for lasso peptides.Journal of industrial microbiology & biotechnology · 2014Review
- Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.Natural product reports · 2013Review
- Ribosomal biosynthesis of α-amanitin in Galerina marginata.Fungal genetics and biology : FG & B · 2012Article
- Colocalization of amanitin and a candidate toxin-processing prolyl oligopeptidase in Amanita basidiocarps.Eukaryotic cell · 2010Article
- Review
- Follow the leader: the use of leader peptides to guide natural product biosynthesis.Nature chemical biology · 2010Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The peptide toxins of poisonous Amanita mushrooms are bicyclic octapeptides (amatoxins) or heptapeptides (phallotoxins). In Amanita bisporigera, alpha-amanitin and phallacidin are synthesized as 35- and 34-amino acid proproteins, respectively, in which the amino acid sequences found in the mature toxins are flanked by conserved amino acid sequences. The presence of invariant Pro residues immediately upstream of the toxin regions and as the last predicted amino acid in the toxin regions themselves suggests that a Pro-specific peptidase is responsible for the initial post-translational processing of the Amanita toxin proproteins. We purified an enzyme from the phalloidin-producing mushroom Conocybe albipes that cleaves a synthetic 22-mer phalloidin peptide to release the mature toxin peptide (AWLATCP). Mass spectrometric analysis of the purified protein combined with isolation and sequencing of the encoding gene indicates that the responsible processing enzyme is a member of the prolyl oligopeptidase (POP) subfamily of proteases (EC 3.4.21.26). The processing enzyme was able to use the chromogenic POP substrate benzyloxycarbonyl-Gly-Pro-p-nitroanilide and was inhibited by the specific POP inhibitor benzyloxycarbonyl-Pro-prolinal. Both Pro bonds in the proprotein are cleaved by the same enzyme, with the C-terminal Pro bond cleaved first or much faster than the N-terminal Pro bond. Transient accumulation of the N-terminal intermediate indicates that cleavage is not strongly processive. A synthetic peptide representing the phallacidin proprotein was also cleaved by the POP of C. albipes, but a precursor of amanitin (which is not made by C. albipes) was cleaved inefficiently.
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