Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives

A final production strain achieved 627 ± 140 mg/L of psilocybin in controlled fed-batch fermentations.

• The biosynthetic production of psilocybin and related compounds was successfully demonstrated in yeast.
• Supplementation with a novel cytochrome P450 reductase improved product yields.
• Additional tryptamine derivatives, including aeruginascin and N-acetyl-4-hydroxytryptamine, were also produced.
• Intermediates and degradation products associated with the psilocybin biosynthesis pathway were detected.
• These findings may enable controlled biotechnological production of psilocybin and other therapeutic tryptamine derivatives.

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