Last week, UW-Madison researchers announced they had created a new form of an enzyme that adds sugar to a variety of chemicals. In the future, researchers hope to use the newly evolved sugar enzymes to improve current drug treatments.
Enzymes serve as the driving force to numerous ongoing biological processes occurring throughout nature. The sugar-happy enzyme, also known as glycotransferase (GT), changes the function of chemicals by adding sugar molecules to them.
The ability of GT to add sugar to chemicals is especially important in the creation and tailoring of “natural drugs,” drugs developed from natural products such as plants, microbes, marine organisms and more.
“Sugars can be used to alter the molecular mechanism of a drug, improve pharmacological properties and decrease unwanted toxicities,” said Jon Thorson, UW-Madison professor of pharmacy and senior author of the study.
While researchers have known for some time that sugars can alter the efficacy of drugs, the ability to promote and control the amount of sugar added or subtracted to drugs has remained just out of reach. Equally challenging to scientists was the fact that GTs are rather selective about what types of chemicals they will offer sugar.
By tinkering with the genes that code for GT, Thorson and others were able to nudge the new enzyme to be more generous with the sweet-stuff. Screening tests revealed the new GT attached sugars to a variety of chemicals.
“Many of the approved anti-infectives and anti-cancer agents derive from natural products,” Thorson said. “The ability to manipulate these very complex molecules holds high promise for drug discovery.”
In the future, Thorson plans to expand his exploration of the properties of GTs and create libraries that document how GTs work to improve currently available drugs.
“This work is a major step forward in generating bacteria specifically engineered to connect sugars with drug-like scaffolds in a single step,” Thorson said. “Such simplified glycosylation studies will greatly advance the discovery of sugar-enhanced drug leads and is likely to have a broad impact in a variety of therapeutic areas.”
