A Mutated Assembly Line Makes Antibiotics


Enzymes manipulated to include targeted mutations could make discovering new antibiotics easier.

A new method developed at North Carolina State Univ. (NCSU) allows researchers to pinpoint particular amino acids in the series of enzymes that make the antibiotic erythromycin. The drug is used to treat a variety of bacterial infections, from the intestinal invader Campylobacter to ear infections to pneumonia.

Erythromycin is produced by a mega enzyme assembly line, called a polyketide synthase, made up of many enzyme modules; each module places a particular small-molecule building block onto the antibiotic’s scaffold structure. Polyketide synthases catalyze the condensation of acyl-CoA thioster building blocks to form the scaffolds of a wide variety of clinically relevant polyketides.

“These assembly lines are analogous to a car assembly line,” says Gavin Williams, an associate professor of bioorganic chemistry at NCSU. Each enzyme, he says, is like a robotic workstation that assembles a particular car part.

Unfortunately, these enzymatic robots are not very flexible in the task they can perform. Each module in the polyketide synthase is specific to its own...

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