( secondary metabolites in that species ...)Mining for gems in the fungal genome

The method developed by Keller and her colleagues solves this problem and promises to broaden the search for medically useful agents by taking a powerful, genome-wide approach. Their technique is called "genomic mining" because of its robust ability to dig through an entire fungal genome to locate nearly all the hidden gems-the actively-produced secondary metabolites-at once.

The key to Keller's approach lies in a single fungal protein called LaeA. A few years ago, her team discovered that the presence of LaeA is required to turn on the genes that manufacture secondary metabolites in Aspergillus nidulans. "LaeA controls the production of secondary metabolites," says Keller.

For some as-yet unknown biological reason, all the genes required for the production of any given secondary metabolite-usually between three and two dozen genes-are located right next to each other along the chromosome in a gene cluster. These groups of genes stand out in certain scientific analyses, making secondary metabolite gene clusters easy to spot. Keller capitalized on these facts to find actively-produced secondary metabolites.

In one experiment, Jin Woo Bok, a research scientist in Keller's lab and co-author on the paper, deleted the LaeA gene in Aspergillus nidulans. Using a device called a microarray, the research team measured the activity of every gene in the LaeA-free mutant. "We looked at the entire 10,000 genes in this fungus," says Keller.

Keller's team searched the genome for groups of contiguous genes that were inactive in the mutant. They knew these were very likely to be gene clusters involved in the production of seco
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Source:University of Wisconsin-Madison