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Pharmaceuticals surrounding a toy human showcasing the gastrointestinal tract
Pharmaceutical ineffectiveness caused by bacterial enzymes in the gastrointestinal tract can cause treatment delays and negative implications for patients. Dr. Xuejun Zhu is working to uncover and characterize those enzymes. | Image: Getty Images
Dr. Xuejun Zhu, assistant professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, was awarded a Welch Foundation grant to help uncover and characterize enzymes involved in modifications that lead to pharmaceutical ineffectiveness. In turn, this could help medical professionals prescribe medications based on an individual’s gut characteristics in the future.

Certain bacteria in the gastrointestinal tract can decrease the effectiveness of pharmaceuticals, potentially causing treatment delays and adverse impacts on individuals’ physical and mental health. Despite research that suggests bacterial enzymes are responsible for modifying the structures and properties of small-molecule pharmaceuticals, these enzymes remain poorly understood.

“There are many pharmaceuticals that are becoming increasingly ineffective,” said Zhu. “They can even have side effects, partly due to certain modifications of the pharmaceuticals by some gut bacteria. The key player in these modifications are enzymes — a kind of protein found in bacteria. Our goal is to determine which enzymes are involved in these changes.”

However, there are hundreds of enzymes, making it difficult to decipher which enzymes are responsible for causing modifications. To help determine these specific enzymes, Zhu and her team will expose substrate specificities — the feature of an enzyme to select the kind of substrate to allow a chemical reaction.

Once they uncover which enzymes are responsible for modifying pharmaceuticals, they will use the information to help predict the enzyme’s unique sequence fingerprints, which determine the substrate specificity and will ease future enzyme discovery.

Moving forward, this research could potentially change the way medicines are prescribed to enhance the effectiveness of medications based on the enzymes in an individual’s gut.

“For example, if we have a fecal sample, we can sequence the DNA or RNA to see which enzymes could be abundant,” said Zhu. “Based on that information, we will be able to determine whether an enzyme will degrade the medication or will likely be more effective. This will hopefully help ensure that what is being prescribed is the most effective treatment for an individual.”

The Welch Foundation is one of the largest private funding resources for chemical research in Texas. The grant supports researchers within the state of Texas who are making significant contributions to chemistry.