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The potential of bacterial gene clusters unlocked in the search for new antibiotics

Resistance to antibiotics has been steadily rising, posing a threat to public health.

Now, a method from , an assistant professor of chemistry at , may open the door to the discovery of a host of potential drug candidates.

The vast majority of anti-infectives on the market today are bacterial natural products, made by biosynthetic . Genome sequencing of bacteria has revealed that these active are outnumbered approximately ten times by so-called silent .

“Turning these clusters on would really expand our available chemical space to search for new antibiotic or otherwise therapeutically useful molecules,” Seyedsayamdost said.

In an article published in the journal Proceedings of the National Academy of Sciences, Seyedsayamdost reported a strategy to quickly screen whole libraries of compounds to find elicitors, small molecules that can turn on a specific . He used a genetic reporter that fluoresces or generates a color when the is activated to easily identify positive hits. Using this method, two were successfully activated and a new metabolite was discovered.

Application of this work promises to uncover new bacterial natural products and provide insights into the regulatory networks that control silent gene clusters.

Source

Seyedsayamdost, M. R. “High-throughput platform for the discovery of elicitors of silent bacterial gene clusters.” Proc. Natl. Acad. Sci. 2014, Early edition doi: 10.1073/pnas.1400019111

Princeton University