Production of biological substances for medicine using genetically engineered yeast cells shows new promising results in basic research from an international team of researchers. In 2022, the researchers attracted international attention by programming the longest-ever biosynthetic pathway - or 'assembly line' - into a microbial cell factory and designing it to produce biological substances 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 treating mental disorders.
"Development of medicines from natural plant substances is widely used. However, since plants do not produce these substances to fight human diseases, there is often a need to modify them to make them more effective and safe," says Michael Krogh Jensen, a senior 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 discovering and developing plant-based medicine.
Fewer side effects for patients
The new research results prove that the engineered yeast cells can make other substances in the group of alkaloids than the substance vinblastine, for which the researchers presented results in 2022. In addition to producing the two new natural plant substances, alstonine and serpentine, the researchers have further developed the method to make 19 new derived variants of the two substances through a chemical process called halogenation, often used in medicine development. Today, up to 40 percent of the substances tested in human trials are produced by halogenation.
"We have found a method to make yeast cells use enzymes and carry out the same chemical process that takes place in halogenation. Plants generally can't naturally carry out halogenation. Therefore, our versatile biotechnological platform is a possible method for optimizing and developing plant-based alkaloids that may then be used to make medicines against, for example, schizophrenia, for which there are many negative side effects such as insomnia, weight gain and reduced immunity, when using existing medicines" says Michael Krogh Jensen.
