Increased psilocybin production in fungi with reduced tryptophan breakdown

A final psilocybin titre of 267 mg/L was achieved in optimized batch cultures.

• Psilocybin is a prodrug of psilocin with potential to treat mental disorders such as depression and alcohol use disorder.
• In Saccharomyces cerevisiae, deleting specific genes increased psilocybin production by fivefold.
• Functional orthologs of key genes were identified in Aspergillus nidulans, which also showed a tenfold increase in psilocybin production upon gene deletion.
• Process optimization through respiratory activity measurements improved the yield of psilocybin in batch cultures.
• The engineered A. nidulans strain may be suitable for large-scale production of psilocybin and other related pharmaceuticals.

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