Yeast cells can produce drugs for treatment of psychotic disorders

An international team of researchers has demonstrated that genetically engineered yeast cells can produce the natural plant product alstonine, which has shown positive effects in treating schizophrenia.

Genetically engineered yeast cells can be used to produce the naturally occurring substance, alstonine, which has shown promising results in terms of being used in the treatment of mental disorders. Photo: Steve Gschmeissner.
The research team behind experiments with genetically engineered yeast cells. From left: Jie Zhang (Co-founder & CSO Biomia), Beata Lehka (postdoc, DTU Biosustain), Samuel Bradley (research assistant, DTU Biosustain), and Michael Krogh Jensen (Co-founder & CEO Biomia, senior researcher DTU Biosustain). Photo: Lea Gram Hansen.

The researchers created the yeast-based cell factories by inserting a large number of genes from plants that can generate biosynthesis of natural plant substances. In addition, they inserted enzymes from bacteria to halogenate these natural substances and tested the production in yeast. Following the conversion into serpentine and alstonine, the substances were purified. The researchers then tested their structure - using an NMR analysis (Nuclear Magnetic Resonance spectroscopy), which looks at the composition of atoms - and investigated their bioactivity in a cell line from monkeys.

Tested in human trials

The researchers have filed a patent application for the manufacture of the chemistry involved and established the company Biomia, which has a license to the patent portfolio that protects the manufacturing method. For drug discovery within part of the chemistry that the researchers presented in their Nature article from 2022 and this new study, Biomia raised 3 million USD in September 2023.

The research into the new yeast-based production of the halogenated plant-inspired natural substances and the 19 variants is still in an early phase, where the researchers are now finding the best candidates to use in treating mental disorders. The candidates must then be prepared for testing in clinical studies. At best, Michael Krogh Jensen expects to be able to send substances derived from alstonine to clinical trials in 2026.

Even if the clinical studies show promising results against schizophrenia or other mental disorders, it will still be at least ten years before the research may lead to new medicines for purchase at pharmacies.

Read the paper in Nature Chemical Biology: Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast 


Michael Krogh Jensen

Michael Krogh Jensen Senior Researcher Novo Nordisk Foundation Center for Biosustainability