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Biological Chemistry

Spilling Bacteria’s Molecular Secrets

Genetic trick might pull back the curtain on potential drugs

by Carmen Drahl
December 10, 2012 | A version of this story appeared in Volume 90, Issue 50

Starting with soil from the Arizona desert, Rockefeller University chemists have hit pay dirt—a small molecule called tetarimycin A that kills methicillin-resistant Staphylococcus aureus in cell cultures (J. Am. Chem. Soc., DOI: 10.1021/ja3093828). They found the molecule by activating biosynthetic gene clusters plucked from the soil. The method has the potential to solve a vexing problem for chemists: Only a small portion of Earth’s microbial inhabitants are easy to culture in a lab, so it’s been tough to study the potentially useful natural products they make. One way around this problem is to pull bacterial DNA from environmental samples and insert natural-product-making genes into easily cultured bacteria, such as certain species of Streptomyces. Oftentimes, though, the genes don’t perform in that unfamiliar milieu. Working with their Arizona soil, Dimitris Kallifidas, Hahk-Soo Kang, and Sean F. Brady found an “on” switch—a transcription factor called tamI. By arranging for transcription to be constantly on, and by combining the transcription factor with the biosynthetic genes, the team isolated the natural product tetarimycin A from a Streptomyces host. The team thinks the strategy should be adaptable for high-throughput screens.


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