U professor discovers new enzyme-friendly antibiotic

The new method of producing medicine will combat drug-resistant bacteria.

Mike Enright

The fight against drug-resistant infections might have just gotten some much needed backup.

Robert Fecik, an assistant professor of medicinal chemistry, together with two University of Michigan colleagues, has developed a new way to make antibiotics.

The new method is hoped to be an important tool in fighting the growing problem of drug-resistant bacteria, and it is also more environmentally friendly than traditional ways of making drugs, Fecik said.

“This (new method) is one way to enable and foster green chemistry,” Fecik said. “Traditional methods use chemicals, not enzymes.”

These methods create toxic chemicals and waste, he said.

Fecik said his team’s research will help with the growing problem of drug resistance because they are looking at antibiotics that can target those kinds of bacteria, and their approach uses technology that should help to make new drugs and new classes of drugs.

J. Todd Weber, director of the anti-microbial resistance office at the Centers for Disease Control and Prevention, said drug-resistant bacteria are “truly a significant problem.”

“And it’s a problem that continues to get worse, despite a lot of good effort to improve our response,” Weber said.

“There is an urgent need for new drugs; new classes of drugs that don’t work in the same way as drugs we already have work,” he said.

Janet Smith, a Michigan professor of biological chemistry who worked with Fecik, said another benefit of their research is that the compounds they are manipulating are bioactive, meaning they easily interact with other living systems.

The bioactive aspect will be beneficial down the road because a drug needs to fulfill its intended function and be able to get into a living system, Smith said.

How it works

“Most antibiotics are made by bacteria,” Fecik said. “What we are trying to do is harness the power of bacteria to make new drugs.”

Bacteria create antibiotics by using proteins called enzymes to take molecules and convert them into ring-shaped antibiotic molecules called macrolides, according to a University Academic Health Center news release.

Molecules enter these enzymes in line formations, but they leave as rings with the ends connected, Smith said.

“One of the big puzzles in this field has been, How does that happen?” Smith said. “What is going on in the enzyme to make the two ends come together?”

Fecik said that before their research no one had been able to see the actual changes going on in the enzymes, so they could only guess what was happening.

“What we’ve discovered is using crystal structures to get a picture of these enzymes as they form the key ring structure to macrolide antibiotics,” Fecik said.

Fecik said he, Smith and fellow Michigan professor David Sherman brought together their three areas of expertise to catch the enzymes in action.

Fecik and former graduate student John Giracles first designed a compound called an “affinity label,” which mimics the compounds normally processed by enzymes.

But unlike the normal compounds, which pass through the enzyme, Fecik’s “affinity label” gets stuck, he said.

Sherman tested the “affinity label” against the enzyme to make sure it would work, and Smith was then able to get a picture of the process and solve the structure of the molecules, Fecik said.