Using evolution, UW team creates a template for many new therapeu...(subtracted to a chemical molecule to alt...)
subtracted to a chemical molecule to alter its therapeutic properties, it is difficult and not always possible to routinely modify them to enhance their beneficial effects.
The new enzyme was created by generating random mutations in genes that make a naturally occurring enzyme. The altered genes were then put into a bacterium, which fabricated a series of randomly mutated new enzymes. These enzyme variants were then tested in a high throughput screen where chemical molecules engineered to fluoresce stop glowing when a sugar is successfully attached.
"We're transferring the sugar to a beacon," Thorson explains. "When you attach a sugar, you shut off the fluorescence."
The development of the screen, according to Thorson, was critical, overcoming a key limitation in the glycosyltransferase field.
"We're assaying hundreds of very interesting drug-like molecules now with newly evolved glycosyltransferases. The ability to rapidly evolve these enzymes has opened a lot of doors."
The range of potential therapeutic agents that might be generated with the new technology includes important anti-inflammatory and anti-cancer compounds, and antibiotics.
What's more, the work could lead to the creation of a "super bug," an engineered bacterium that can perform the entire process in a laboratory dish: "There's no doubt that this is going to work in vivo," says Thorson. "We can create a bug where you feed it sugars and the compounds you want to hang those sugars on" to arrive at new medicines.
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| Contact: Jon Thorson jsthorson@pharmacy.wisc.edu 608-262-3829 University of Wisconsin-Madison Source:Eurekalert |
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