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Unlocking potential of bacterial gene clusters to discover new antibiotics

Date:
May 20, 2014
Source:
Princeton University
Summary:
A method for activating biosynthetic silent gene clusters could aid in the discovery of new antibiotics, researchers report. The vast majority of anti-infectives on the market today are bacterial natural products, made by biosynthetic gene clusters. Genome sequencing of bacteria has revealed that these active gene clusters are outnumbered approximately ten times by so-called silent gene clusters.

A new method developed at Princeton could lead to the discovery of new antibiotic compounds. Mohammad Seyedsayamdost, an assistant professor of chemistry at Princeton University, has devised a high-throughput screening strategy to activate silent biosynthetic gene clusters, which are not expressed under normal circumstances. The strategy will help researchers explore the products made by these gene clusters and the signals that lead to their activation.
Credit: Mohammad Seyedsayamdost

Resistance to antibiotics has been steadily rising, posing a threat to public health. Now, a method from Mohammad Seyedsayamdost, an assistant professor of chemistry at Princeton University, may open the door to the discovery of a host of potential drug candidates.

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

"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 gene cluster. He used a genetic reporter that fluoresces or generates a color when the gene cluster is activated to easily identify positive hits. Using this method, two silent gene clusters 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.


Story Source:

The above story is based on materials provided by Princeton University. The original article was written by Tien Nguyen. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. R. Seyedsayamdost. High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1400019111

Cite This Page:

Princeton University. "Unlocking potential of bacterial gene clusters to discover new antibiotics." ScienceDaily. ScienceDaily, 20 May 2014. <www.sciencedaily.com/releases/2014/05/140520123519.htm>.
Princeton University. (2014, May 20). Unlocking potential of bacterial gene clusters to discover new antibiotics. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/05/140520123519.htm
Princeton University. "Unlocking potential of bacterial gene clusters to discover new antibiotics." ScienceDaily. www.sciencedaily.com/releases/2014/05/140520123519.htm (accessed November 28, 2014).

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