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Researchers Tweak Enzyme ‘Assembly Line’ to Improve Antibiotics

In Associate Professor Gavin Williams' lab, researchers are learning how to make hybrid assembly lines.

In Associate Professor Gavin Williams’ lab, researchers are learning how to make hybrid assembly lines.

Researchers have discovered a way to make pinpoint changes to an enzyme-driven “assembly line” that will enable scientists to improve or change the properties of existing antibiotics as well as create designer compounds. The work is the first to efficiently manipulate which building blocks the enzyme selects in the act of synthesizing erythromycin, an important antibiotic.

Many antibiotics are synthesized by huge sets of enzymes called polyketide synthases, a series of proteins arranged in a particular order that recruit specific small-molecule building blocks to assemble the drug of interest. Picture an automobile assembly line—a car is assembled sequentially, using various interchangeable parts as it moves from one workstation to the next in line. Drug synthesis via polyketide synthases works in much the same way. Each protein module acts as a workstation responsible for selecting and adding another specific building block to the antibiotic.

Improving upon existing antibiotics is an efficient way to create new drugs in terms of both time and cost. If researchers could manipulate the function of each module in the enzyme assembly line, it would allow them to design man-made molecules, thus fine-tuning the pharmacological properties of a drug. However, no one had been able to discover how to make small tweaks to an enzyme module in order to completely change which building blocks are selected during the assembly process.

Gavin Williams, associate professor of bio-organic chemistry at NC State, is corresponding author of a paper describing the work, along with several current and former Ph.D. students.

This article was originally published by NC State News.