The Australian Genome Foundry (AGF) is developing a novel approach to improve the production of psilocybin, an emerging therapeutic compound being investigated for conditions including treatment-resistant depression, substance dependence and end-of-life anxiety.
Psilocybin can be extracted from fungi, but natural production is limited by variable and relatively low yields. Chemical synthesis can also be costly, creating a need for more efficient and scalable manufacturing approaches. This project is exploring how biotechnology can provide an alternative by using baker’s yeast, Saccharomyces cerevisiae, as a biological production platform.
The team is combining Ancestral Sequence Reconstruction with Adaptive Laboratory Evolution to effectively rewrite the evolutionary history of enzymes involved in psilocybin production. By reconstructing ancient versions of these enzymes and introducing them into modern yeast, the researchers aim to identify high-performing combinations and ultimately evolve yeast strains capable of producing greater quantities of psilocybin.
AGF has reconstructed ancestral versions of the four enzymes in the psilocybin pathway, engineered yeast strains and developed an LC-MS method to reliably detect and quantify psilocybin.
Supported by AGF’s automation, analytical chemistry and high-throughput engineering capabilities, the project demonstrates how advanced genomics and biotechnology can enable new approaches to sustainable biomanufacturing.