A newly characterized enzyme from the psilocybin mushroom Psilocybe cubensis, called PcncAAAD, can decarboxylate several aromatic amino acids—including L-tryptophan, L-phenylalanine, and L-tyrosine—as well as chloro-tryptophan derivatives. Unlike previously known aromatic L-amino acid decarboxylases (AAADs) in mammals and plants, this enzyme belongs to a different protein family and contains a unique C-terminal double-β-barrel domain that binds calcium, which is required for its activity and thermal stability. The enzyme likely contributes to psilocybin biosynthesis and offers a new tool for engineering production of aromatic-amino-acid-derived natural products.
Kava, a medicinal plant used for over 3,000 years in Polynesia, produces kavalactones—compounds that reduce anxiety and pain through mechanisms distinct from benzodiazepines and opioids. This work identifies the seven enzymes that build kavalactones, showing that two of them evolved from an ancestral enzyme to create the core kavalactone structure. Further enzymes then modify this scaffold to generate diverse kavalactones. The pathway was successfully transplanted into bacteria, yeast, and plants, enabling production of kavalactones and their derivatives. This opens a route to developing new treatments for anxiety disorders, which affect over 260 million people worldwide.