Saccharomyces cerevisiae — baker's yeast. Credit: Bob Blaylock
Key points:
- Researchers have developed a new screening method that makes it much more efficient to identify how and which plants can synthesize medicinal compounds.
- The screening method is based on baker’s yeast, which helps capture protein-protein interactions between plant enzymes.
- The new method led to the identification of six kratom enzymes from 20 candidates.
Aspirin, morphine and some chemotherapies are examples of drugs that are derived from natural compounds produced by plants. But, identifying the genes that allow plants to create such compounds is tedious and expensive.
Now, Cornell University researchers have created a cost-effective and highly efficient approach—using baker’s yeast. They even used the new method to identify key enzymes in a kratom tree.
According to their study in Angewandte Chemie, the new yeast-based screening method captures protein-protein interactions between plant enzymes, working in tandem with other screening methods to better pinpoint which genes are ultimately responsible for how a plant biosynthesizes medicinal compounds.
“Traditional methods find groups of proteins that exist in the plant at the same time, but our method complements that by looking at which of those groups physically cluster and play well with each other,” said Sijin Li, assistant professor of chemical and biomolecular engineering and lead author of the study. “Those are the ones responsible for the type of chemicals we might want to extract for a pharmaceutical.”
Once gene candidates are predicted using plant transcriptomics, baker’s yeast—the same kind used for brewing beer and baking bread—is engineered with the genes inside to see which ones produce proteins that interact with each other. As a result, the number of genes that must then be biochemically screened is significantly reduced.
In experiments with kratom leaves—which is not well studied but is thought to have pharmaceutical potential—the yeast-based method led to the identification of six kratom enzymes from 20 candidates predicted by genetic screening to produce mitragynine or other targeted chemicals. Subsequent biochemical testing showed that none of the 14 discarded candidates were functional enzymes, while four of the six identified by the yeast-based method were functional.
“For clinical trials, the chemical has to be purified from the plant or synthesized using a chemical approach, which is very expensive,” Li said. “Using the yeast method, we can more economically produce mitragynine and other chemicals that might lead us to new pharmaceuticals.”