Modified E. coli pump out psilocybin

A team of chemical engineers engineered the bacterium Escherichia coli to produce large quantities of psilocybin, the psychoactive compound in magic mushrooms. The work, published in Metabolic Engineering, addresses the challenge of manufacturing psilocybin as it enters clinical trials for depression and other brain conditions. The fungal enzymatic pathway for psilocybin was only described in 2017; it starts with a tryptophan-based compound and ends with a phosphorylated product. The phosphate group is unstable in synthetic chemistry but readily added by biological systems, and in the human body it is removed to form psilocin, which crosses the blood-brain barrier.

Study at a glance

Abstract

A team of researchers has turned Escherichia coli into tiny bioreactors that can manufacture large amounts of psilocybin, the ingredient in magic mushrooms that leads to their psychoactive effects (Metab. Eng. 2019, DOI: 10.1016/j.ymben.2019.09.009). With the compound in clinical trials for treating depression and other brain diseases, says J. Andrew Jones, the Miami University chemical engineer who led the work, scaled-up manufacturing processes may soon be needed to meet consumer demand. Scientists discovered psilocybin decades ago, but the enzymatic pathway that fungi use to make the molecule wasn't described until 2017. That synthesis, scientists found, starts with a tryptophan-based compound and ends with a phosphorylated product. The phosphate on psilocybin is unstable, however, and in the human body, it's stripped to make psilocin, which can cross the blood-brain barrier, Jones says. So getting that phosphate onto psilocybin is challenging with synthetic methods, he says, but "biology is good at adding