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The production of biological substances for medicines using genetically engineered yeast cells shows new promising results in fundamental research by an international team of researchers. In 2022, the researchers attracted international attention by programming the longest biosynthetic pathway ever – or “assembly line” – into a microbial cell factory and designing it to produce biological compounds for cancer drugs.
In an article published in the scientific journal Nature Chemical Biology, Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast, the researchers now present results with the artificial production of the naturally occurring substance, alstonine, which has shown promising results for use in the treatment of mental illness.
“The development of medicines based on natural plant substances is widely used. However, because plants do not produce these substances to combat human diseases, it is often necessary to modify them to make them more effective and safer,” says Michael Krogh Jensen, a senior researcher. researcher at DTU Biosustain and co-founder of the biotech company Biomia.
The researchers hope that the yeast platform can play a prominent role in the discovery and development of plant-based medicines.
Fewer side effects for patients
The new research results prove that the manipulated yeast cells can produce substances from the alkaloid group other than the substance vinblastine, for which the researchers presented results in 2022. In addition to producing the two new natural plant compounds, alstonin and serpentine, the researchers further developed the method to create 19 new derivative variants of the two compounds through a chemical process called halogenation, which is commonly used in the development of medicines. Today, up to 40 percent of substances tested in human trials are produced by halogenation.
“We have found a method to get yeast cells to use enzymes and perform the same chemical process that occurs in halogenation. Plants generally cannot halogenate naturally. Therefore, our versatile biotechnological platform is a possible method for optimizing and developing plant-based alkaloids that can then be used to make drugs against, for example, schizophrenia, for which there are many negative side effects such as insomnia, weight gain and reduced immunity, when using existing drugs,” says Michael Krogh Jensen.
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