by Researchers from Cornell University have developed a cost-effective and highly efficient method using baker’s yeast to unravel how plants synthesize medicinal compounds. This new approach has been successfully applied to the identification of key enzymes in a kratom tree.
Many drugs, including aspirin, morphine, and certain chemotherapies, are derived from natural compounds produced by plants. The process of understanding how a plant creates these compounds typically involves analyzing plant transcriptomes to identify hundreds of potential genes that may code for the enzymes responsible for synthesis. Each gene must then be further characterized through biochemical screening, using specific substrates and reaction conditions. However, this process is time-consuming and costly, which often hinders the discovery of new medicinal compounds.
The researchers published their yeast-based screening method in the journal Angewandte Chemie. This novel technique captures protein-protein interactions between plant enzymes, working alongside other screening methods to pinpoint the genes responsible for the biosynthesis of medicinal compounds more accurately.
Sijin Li, assistant professor of chemical and biomolecular engineering and lead author of the study, explained, “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. Those are the ones responsible for the type of chemicals we might want to extract for a pharmaceutical.”
The new approach greatly streamlines the process of biochemical screening. After predicting gene candidates using plant transcriptomics, the researchers engineered baker’s yeast to carry these genes to observe which ones produce proteins that interact with each other. This method reduces the number of genes that need to undergo biochemical screening significantly.
Li emphasized the potential of this method, stating, “This technique, which had been underutilized for pathway discovery, eliminates a big bottleneck for high-throughput screening. It’s cheaper and safer than using chemical substrates, and it’s highly efficient and accurate.”
To demonstrate the effectiveness of the yeast-based approach, the research team focused on kratom leaves. Kratom is a tropical tree native to Southeast Asia that has gained attention due to its pharmaceutical potential. The tree produces a chemical called mitragynine, which has a painkilling effect similar to opioids but does not cause dangerous respiratory depression. While the U.S. Food and Drug Administration has issued warnings regarding the use of kratom, the research aims to extract pure mitragynine, which would eliminate the risks associated with the use of the entire kratom matrix and potentially lead to safer treatments.
Through the yeast-based method, the researchers identified six kratom enzymes out of 20 candidates that were predicted to produce mitragynine or other targeted chemicals. In subsequent biochemical testing, it was determined that none of the discarded candidates were functional enzymes, while four out of the six identified by the yeast-based method were functional. This highlights the accuracy and potential efficiency of the method, allowing for the discovery of new medicinal compounds and further study of the kratom tree.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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