Gene family encoding the major toxins of lethal <i>Amanita</i> mushrooms

<jats:p> Amatoxins, the lethal constituents of poisonous mushrooms in the genus <jats:italic>Amanita</jats:italic> , are bicyclic octapeptides. Two genes in <jats:italic>A. bisporigera</jats:italic> , <jats:italic>AMA1</jats:italic> and <jats:italic>PHA1</jats:italic> , directly encode α-amanitin, an amatoxin, and the related bicyclic heptapeptide phallacidin, a phallotoxin, indicating that these compounds are synthesized on ribosomes and not by nonribosomal peptide synthetases. α-Amanitin and phallacidin are synthesized as proproteins of 35 and 34 amino acids, respectively, from which they are predicted to be cleaved by a prolyl oligopeptidase. <jats:italic>AMA1</jats:italic> and <jats:italic>PHA1</jats:italic> are present in other toxic species of <jats:italic>Amanita</jats:italic> section <jats:italic>Phalloidae</jats:italic> but are absent from nontoxic species in other sections. The genomes of <jats:italic>A. bisporigera</jats:italic> and <jats:italic>A. phalloides</jats:italic> contain multiple sequences related to <jats:italic>AMA1</jats:italic> and <jats:italic>PHA1</jats:italic> . The predicted protein products of this family of genes are characterized by a hypervariable “toxin” region capable of encoding a wide variety of peptides of 7–10 amino acids flanked by conserved sequences. Our results suggest that these fungi have a broad capacity to synthesize cyclic peptides on ribosomes. </jats:p>