Revealing nature’s antibiotic factories
Many of the drugs that are now in use are actually made by bacteria and fungi. These microbes make compounds that kill competing microbes or that provide themselves with a growth advantage.
Dr. Martin Schmeing, Canada Research Chair in Macromolecular Machines, is studying a class of proteins called nonribosomal peptide synthetases (NRPS), which synthesize (or put together) these compounds in microbes. NRPSs produce a myriad of compounds that can interact with living tissues or systems. These include penicillin (the first widely-used antibiotic), viomycin (an antibiotic used to treat multidrug-resistant tuberculosis) and cyclosporine (which is used as an immunosuppressant in organ transplants).
Schmeing is expanding the knowledge of the mechanisms these proteins use to synthesize important drugs. He is using a number of techniques to understand how building blocks are chemically assembled into antibiotics, how NRPSs undergo the large-scale rearrangements needed to make these drugs, and other matters.
NRPSs hold a vast potential to produce new drugs. Because NRPSs are divided into segments, with each segment adding one building block to the drug, it is possible to switch the order and specific type of segments to produce new variants of the drug.
Schmeing’s research will provide better understanding of how to best rearrange NRPS segments. His work could result in millions of new compounds, including drugs to fight antibiotic resistant bacteria, viruses and cancer.