Janis Fricke, Felix Blei, and Dirk Hoffmeister of Friedrich Schiller University Jena have identified and characterized to the greatest extent so far the four enzymes that the mushrooms use to make psilocybin. The team then developed the first enzymatic synthesis of the compound, setting the stage for its possible commercial production (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201705489).

During their study, Hoffmeister and coworkers sequenced the genomes of two mushroom species to identify the genes that govern fungal enzymatic production of psilocybin. They further used engineered bacteria and fungi to confirm the gene activity and exact order of synthetic steps. This process includes a newly discovered enzyme that decarboxylates tryptophan, an enzyme that adds a hydroxyl group, an enzyme that catalyzes phosphorylation, and an enzyme that mediates two sequential amine methylation steps. With that knowledge in hand, the team designed a one-pot reaction using three of the enzymes to prepare psilocybin from 4-hydroxy-L-tryptophan.