Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives
Metabolic Engineering March 26, 2020 N. Milne, Philip Tinggaard Thomsen, Niels Aage Tvis Knudsen et al. 126 citations
Psilocybin, the psychoactive alkaloid in magic mushrooms, shows promise for treating psychological and neurological disorders. By inserting genes from Psilocybe cubensis into Saccharomyces cerevisiae, researchers engineered yeast to produce psilocybin and related compounds from scratch. Adding a novel cytochrome P450 reductase from P. cubensis improved yields. In controlled fed-batch fermentations, the final strain produced 627 ± 140 mg/L of psilocybin and 580 ± 276 mg/L of psilocin. Intermediates baeocystin, norbaeocystin, and norpsilocin were also detected. The method also produced natural aeruginascin and a new-to-nature derivative, N-acetyl-4-hydroxytryptamine, laying groundwork for controlled biotechnological production for pharmaceuticals.