Scientists design engineered yeast to produce complex cancer drug, will save a lot of flowers
Madagascar periwinkle (C. roseus) is a flowering plant that has been used in traditional medicine for thousands of years and as a source of the chemotherapy drugs vinblastine and vincristine since the 1950s. Vincristine interferes with cell division and is used to treat lymphoma, breast, bladder, and lung cancer, among others, while vincristine can be used to treat leukemia due to its ability to inhibit the production of white blood cells.
Both are on the World Health Organization’s list of essential medicines, but frustratingly, they could be affected by shortages. That’s because it takes a lot of plants to produce usable quantities of the drug — 500 kilograms of dried leaves are needed to make one gram of vinblastine, and 2,000 kilograms of vincristine.
Making synthetic versions in the lab might seem like the obvious solution, but the complexity of these molecules means scientists haven’t found one so far. In the new study, researchers at Berkeley Lab and the Technical University of Denmark (DTU) turned to microbes for help, using commonbreadYeast to produce drug precursors.
The team made a total of 56 gene edits to the yeast genome, including adding 34 plant genes, while deleting, suppressing and overexpressing other genes native to the microbe. Yeast requires 30 steps to produce two molecules, catharanthine and vindoline, which are precursors to vinblastine. In the 31st and final step of the process, the scientists then combine these molecules to make a drug.
While the team has not specified how many drugs the yeast is capable of producing, this proof-of-concept study should show that, with further work, the microbial factory can be scaled up to make vinblastine and related therapeutic molecules, which are difficult to extract from Extracted from natural sources.
Jay Keasling, co-leader of the project, said: “The yeast platform we have developed will allow the production of vinblastine and more than 3,000 other molecules belonging to this family of natural products in an environmentally friendly and affordable manner. In addition to vinblastine, this platform will be able to produce anti-addiction and anti-malarial therapies as well as treatments for many other diseases.”
The study was published innature” magazine.