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IMAGE: The synthesis of the potent antibiotic thiostrepton uses a radical SAM protein TsrM, whose crystal structure is shown at left while bound to an iron-sulfur cluster and cobalamin. New images...
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Credit: Booker Lab, Penn State
UNIVERSITY PARK, Pa. -- Images of a protein involved in creating a potent antibiotic reveal the unusual first steps of the antibiotic's synthesis. The improved understanding of the chemistry behind this process, detailed in a new study led by Penn State chemists, could allow researchers to adapt this and similar compounds for use in human medicine.
"The antibiotic thiostrepton is very potent against Gram-positive pathogens and can even target certain breast cancer cells in culture," said Squire Booker, a biochemist at Penn State and investigator with the Howard Hughes Medical Institute. "While it has been used topically in veterinary medicine, so far it has been ineffective in humans because it is poorly absorbed. We studied the first steps in thiostrepton's biosynthesis in hopes of eventually being able to hijack certain processes and make analogs of the molecule that might have better medicinal properties. Importantly, this reaction is found in the biosynthesis of numerous other antibiotics, and so the work has the potential to be far reaching."