August 7, 2015

Bridging the antibiotic gap

Vanderbilt researchers have discovered how certain molecules with antibiotic properties are synthesized, findings that could lead to new drugs that overcome the increased antibiotic resistance in bacteria.

Antibiotics are the mainstay in a doctor’s toolkit. However, extensive use of antibiotics has also led to increased resistance in bacteria, prompting the search for new antibiotics.

Orthosomycins, which are produced by terrestrial bacteria, exhibit broad-spectrum antibiotic properties. They have a unique scaffold, or structure, which may reduce the potential for bacterial resistance. However, it has been difficult to make these compounds because their biosynthetic pathway was unknown.

Until now.

With Brian Bachmann, Ph.D., whose group mines microbes in odd places, including caves, for their pharmaceutical potential, Tina Iverson, Ph.D., and colleagues have solved a 50-year-old mystery.

In a paper published online this week by the Proceedings of the National Academy of Sciences, they show that bacterial enzymes called oxygenases assemble a chemical structure, the orthoester linkage, required for orthosomycin’s antibiotic activity.

By inserting an oxygen molecule between two sugars to close a ring of carbon chains, oxygenases play a key role in the production of orthosomycin antibiotics, the researchers concluded.

The study was supported in part by National Institutes of Health grants HL007751 and RR026915.

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