Compiled by Mike Retzlaff
In the summer and fall of 2019, certain cancer treatment drugs became unavailable and many cancer patients suffered from non-treatment. These drugs, vinblastine and vincristine, are crucial medications for several types of cancer.
There are no known alternatives to these drugs. The two active ingredients, Vindoline and catharanthine, combine to form vinblastine which inhibits the division of cancer cells. They are isolated from the leaves of the Madagascar periwinkle plant. This is a common plant but it takes more than 2,000 kilograms of dried leaves to produce 1 gram of vinblastine.
The shortage which lasted until 2021, was due to supply chain delays.
The Technical University of Denmark (DTU) leads an international team of scientists who have worked to genetically engineer yeast to produce the basic chemicals and to purify and combine the two to form vinblastine. A new synthetic procedure to produce these drugs has been developed.
This research should result in a source for the drugs which is sustainable and less vulnerable. They can now be independent of the downside of farming such as plant disease, drought, weather anomalies, and other natural disasters.
The essential ingredients needed to make these compounds are yeast (Saccharomyces) and renewable substrates such as sugars and amino acids. Laboratory production is virtually immune to pandemics and global logistics problems.
Vinblastine belongs to a group called monoterpene indole alkaloids (MIAs). MIAs are biologically active and useful in treating various diseases. However, they are highly complex molecules and, therefore, difficult to produce synthetically. This study aimed to prove that the researchers could do it.
The team performed 56 genetic edits to program the 31-step biosynthetic pathway into yeast. Though the work was difficult, tedious, and further work is needed, the researchers expect that yeast cells will be a scalable platform for producing more than 3,000 naturally-occurring MIAs and millions of new-to-nature analogues in the future.
The project was designed to look for new ways of manufacturing a complex chemistry essential for human health. The technology may also be useful in agricultural sciences and other problem areas. Biotechnology offers something exciting because chemical synthesis is difficult to scale, and natural resources are finite. This provides a needed third approach: fermentation or whole-cell manufacturing. Nature’s assembly lines are plugged into microbial cells and allow the cells to produce some of these complex chemicals in the laboratory.
Once again, yeast has risen to the aid of human endeavor. Yeast has served mankind in baking and brewing for millennia which apparently is only the beginning of its usefulness.
Referenced from an article in NATURE Journal of 8/2022
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