New understanding of antibiotic synthesis | 1/13/2016 | Staff
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Researchers at McGill University's Faculty of Medicine have made important strides in understanding the functioning of enzymes that play an integral role in the production of antibiotics and other therapeutics. Their findings are published in Science.

"Many of the medicines that we rely on today are natural products, made by the Earth's flora," explains Dr. Martin Schmeing, Associate Professor in the Department of Biochemistry at McGill and the study's senior author. "This includes compounds made in microbes by massive enzymes called nonribosomal peptide synthetases, or NRPSs. NRPSs synthesize all sorts of antibiotics, which can kill dangerous fungi and bacteria, as well as compounds to help us fight off viral infections and cancers. For example, these compounds include viomycin, an antibiotic used for the treatment of multidrug-resistant tuberculosis; cyclosporin, which has been widely used as an immunosuppressant in organ transplants; and the familiar antibiotic penicillin."

Order - Drugs - NRPSs - Factory - Line

In order to synthesize these drugs, NRPSs operate similar to a factory assembly line, consisting of a series of workstations. Each station, called a "module," has multi-step workflows and moving parts that allow it to add one building block component to the growing drug.

Previous work by Dr. Schmeing and others has led to a solid understanding of how one module works. Now, using a technique called X-ray crystallography at the Canadian Light Source in Saskatchewan, and the Advanced Photon Source in Illinois, the team was able to take ultra-high resolution 3-D pictures of the NRPSs.

Time - Quality - Observations - Module - Assembly

For the first time, they were able to make high quality observations about how an individual module relates to the bigger assembly line, by visualizing a two-module portion of the NRPSs that makes the antibiotic linear gramicidin (found in Polysporin treatments). The study found a surprising lack of synchronisation between modules at all points other than when they must coordinate to pass the intermediate...
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