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How to Make Novel Antibiotics from Scratch

A method for designing novel compounds could help defeat drug-resistant bacteria

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It's hard to imagine a world without antibiotics, but because of widespread overuse of the drugs, that's where we're headed. The Centers for Disease Control and Prevention says that in the U.S. alone, more than 23,000 people now die every year from infections that antibiotics can no longer cure. A study commissioned by the U.K. government estimated that by 2050, antibiotic resistance will cause 10 million deaths worldwide annually. Scientists have struggled to develop new drugs that can kill these superbugs. Consider the major class of antibiotics called macrolides, which treat common bacterial infections, including pneumonia, strep throat, ear and skin infections, and sexually transmitted diseases.

Researchers have tried to revamp the chemistry of these antibiotics to make them more effective against resistant strains, but they have had little success so far. The chemical structure of macrolides is difficult to manipulate, and the raw materials that go into making them are produced in large vats of industrial bacteria—not an easy process to tweak with any precision. “Chemists have been hamstrung for decades,” says Andrew Myers, a professor of chemistry and chemical biology at Harvard University.

Recently, though, Myers and his team figured out a practical method for creating macrolides from the ground up. To do this, they break down the structure of macrolides into eight simple building blocks and then reconstruct them in different forms, tinkering with the chemistry as they go. In a research paper published this past May in Nature, Myers's group reported synthesizing more than 300 novel compounds. Tested against 14 pathogenic bacteria, the majority kept microbes at bay, and some could conquer drug-resistant strains.


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Since then, the researchers have made another 500-plus new compounds, and Myers has started a company, Macrolide Pharmaceuticals, to commercialize drugs produced by the process. The group has begun work on two additional classes of antibiotics, lincosamides and aminoglycosides. Only a handful of the compounds they create will become practical antibiotics, and even those have a long way to go before they reach pharmacies. But Myers is hopeful that research such as his own will help defeat superbugs. “I have every optimism that as we continue to explore,” he says, “this is only going to get better”.

Annie Sneed is a science journalist who has written for the New York Times, Wired, Public Radio International and Fast Company.

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Scientific American Magazine Vol 315 Issue 6This article was published with the title “2. New Antibiotics from Scratch” in Scientific American Magazine Vol. 315 No. 6 (), p. 35
doi:10.1038/scientificamerican1216-35a

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