Structural basis for psilocybin biosynthesis.
Nature communications March 22, 2025 Chunyan Meng, Wenting Guo, Chuan Xiao et al. 4 citations
Psilocybin, a compound from psychedelic mushrooms, shows promise for treating psychiatric conditions when used in therapy. A biosynthetic method could produce psilocybin quickly and efficiently, and understanding the enzymes involved can improve this process. Researchers determined the crystal structures of three key enzymes—PsiD, PsiK, and PsiM—in various forms, revealing how they work together to convert L-tryptophan into psilocybin. The structures show self-cleavage and self-inhibition mechanisms in PsiD and the stepwise catalytic sequence. Tests on female mice with depression-like behaviors demonstrated antidepressant effects from biosynthetic intermediates, particularly norbaeocystin, highlighting its clinical potential.