In vivo production of psilocybin in E. coli

Sep 25, 2019Metabolic engineering

Producing Psilocybin Inside Living E. coli Bacteria

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Abstract

A production titer of 1.16 g/L of psilocybin was achieved in a recombinant organism.

The psilocybin production platform was developed in Escherichia coli.
A 32-fold improvement in psilocybin production was observed through genetic optimization techniques.
Fermentation optimization further enhanced production capabilities.
This achievement is associated with the highest psilocybin titer reported from a recombinant organism to date.
The findings suggest potential for industrial-scale production of biologically-derived psilocybin.

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Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.

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In vivo production of psilocybin in E. coli

Abstract

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