LAWRENCE — Genetic research involving fungi being conducted at the University of Kansas could lead to treatments for a variety of diseases such as cancer and osteoporosis.

Fungi have long been known to contain chemical compounds that inhibit harmful biological processes. A team of researchers including Berl Oakley, the Irving S. Johnson Distinguished Professor of Molecular Biology at KU, has developed a method to activate genes of the fungus Aspergillus nidulans to produce such compounds, also known as secondary metabolites.

“Fungal secondary metabolites are a rich source of medically useful compounds. Our work is leading to the rapid discovery of new compounds, and they are being evaluated for potential medical utility,” Oakley said.

Useful medical compounds found in fungi include penicillin, lovastatin and terrequinone. Various fungi produce antibiotics such as penicillin to inhibit the growth of bacteria that compete with the fungi for nutrients. More recently, the compound lovastatin was found to inhibit the production of cholesterol, and terrequinone was shown to fight tumors.

After earlier research sequenced the genome of Aspergillus nidulans, scientists realized this model organism had the potential to make many more secondary metabolites than were produced under normal laboratory conditions. Each potentially could be a disease-fighting chemical compound.

“In nature, they are probably made in response to particular environmental conditions or competing organisms, but in the lab they are not produced,” Oakley said.

Oakley’s study changes this. His team has found a way to activate genes to produce more medically useful compounds within a lab setting. They discovered that the regulation of production of some secondary metabolites occurs at the chromatin level. Chromatin is a collection of proteins packed around DNA. By genetically manipulating chromatin, Oakley’s team stimulated production of a group of secondary metabolites that normally would not be produced in significant amounts in a lab. This approach will allow researchers to discover new secondary metabolites and understand the biochemical pathways that produce them. They have also discovered how to delete or modify genes in the biochemical pathways, which also leads to the production of additional compounds.

Oakley’s team published this research in May in the journal Nature Chemical Biology in a brief commentary, “Chromatin-level Regulation of Biosynthetic Gene Clusters.”

Oakley’s research is part of a more than $4 million, five-year program project, “Mining the Aspergillus Nidulans Secondary Metabolome,” funded by the National Institutes of Health. Clay Wang of the University of Southern California and Nancy Keller of the University of Wisconsin are also funded by the project. The project uses the complementary expertise of the three labs to accelerate the pace of the research. Oakley initiated the project while at Ohio State University but began research soon after his arrival at KU last fall.

Contact: Debra Simon, Higuchi Biosciences Center, (785) 864-5209, Email: kunews@ku.edu

Source: The University of Kansas