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Mining for gems in the fungal genome

Ever since penicillin, a byproduct of a fungal mold, was discovered in 1929, scientists have scrutinized fungi for other breakthrough drugs. As reported Jan. 20 in the Journal of Chemistry and Biology, a team led by a University of Wisconsin-Madison researcher has developed a new method that may speed the ongoing quest for medically useful compounds in fungi.

By manipulating a single fungal protein, the team, led by professor of plant pathology and medical microbiology Nancy Keller, pinpointed the genes responsible for creating dozens of secondary metabolites, a class of compounds that make good drug candidates. Already, analysis of one subset of these genes has revealed that they encode proteins required to produce an anti-tumor agent.

"We now have a new tool we can use to find secondary metabolites that are of pharmaceutical interest," says Keller. Although the team worked on a widely studied fungus, Aspergillus nidulans, the method can be used to find secondary metabolites in many other fungal species.

While primary metabolites are essential compounds that aid basic growth and reproduction in fungi, secondary metabolites are not required for life. "Secondary metabolites are bioactive compounds that are only produced at select times during the life cycle of the organism," explains Keller, noting that the compounds can help fungi survive various environmental stressors.

Some secondary metabolites have powerful heath effects in humans, such as penicillin, which certain fungi produce in the presence of bacteria. Fungi are also natural producers of antiviral agents, antifungals, other antibacterials, immunosuppressants and the popular cholesterol-lowering drug lovastatin.

Earlier methods to find secondary metabolites located just one compound at a time, and sometimes required prior knowledge about the compound of interest. Even after the genetic sequence of Aspergillus nidulans was completed in 2003, the search for
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Source:University of Wisconsin-Madison


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