ACS Chemical Biology
November 28, 2018
Michael P. Torrens-Spence, Chun‐ting Liu, Tomáš Pluskal et al.
40 citations
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.
bioRxiv Preprint Server
April 4, 2018
Tomáš Pluskal, Michael P. Torrens-Spence, Timothy R. Fallon et al.
3 citations
preprint
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.
Communications Biology
February 26, 2026
Tianjie Li, Erin. E. Reynolds, Ziqi Wang et al.
A fungal enzyme called PcncAAAD, which decarboxylates aromatic amino acids, is activated by calcium through two metal-binding sites. The primary activation site (site A) lies between the N-terminal domain and a unique C-terminal appendage; binding calcium there stabilizes a 'lid-rim' structure that preserves the substrate-binding pocket. A secondary site (site B) within the C-terminal domain helps stabilize the enzyme's overall structure. Computer simulations and lab tests show that disrupting site A or the lid-rim severely distorts the active site and reduces or eliminates activity. Sodium does not activate the enzyme. The work clarifies how calcium activates this enzyme and may guide engineering of similar enzymes for making aromatic amino acid derivatives.
Research Square
April 28, 2025
Yi Wang, Tianjie Li, Erin S. Reynolds et al.
An enzyme called PcncAAAD, a noncanonical aromatic L-amino acid decarboxylase, is activated by calcium through a specific mechanism. Using computer simulations and lab experiments, researchers identified two calcium-binding sites: site A, at the junction of two enzyme domains, primarily drives activation, while site B within a unique tail domain stabilizes the enzyme's structure. Calcium binding at site A stabilizes a 'lid-rim' structure that maintains the substrate-binding pocket. Mutations disrupting site A or this lid-rim severely distort the active site and reduce or eliminate enzyme activity. These findings clarify how calcium activates this enzyme and may aid in designing enzymes to produce aromatic amino acid derivatives.