Technology Unlocks Mold Genomes For New Drugs.





Science, 13 Jun - 2017 ,

Technology Unlocks Mold Genomes For New Drugs.
Credit: Northwestern University

Fungi are rich sources of natural molecules for drug discovery, but numerous challenges have pushed pharmaceutical companies away from tapping into this bounty.

Fungi are rich sources of natural molecules for drug discovery, but numerous challenges have pushed pharmaceutical companies away from tapping into this bounty. Now scientists at Northwestern University, the University of Wisconsin-Madison and the biotech company Intact Genomics have developed technology that uses genomics and data analytics to efficiently screen for molecules produced by molds to find new drug leads — maybe even the next penicillin.

Scientists believe there are thousands or even millions of fungal molecules waiting to be discovered, with enormous health, social and economic benefits. The new technology systematically identifies powerful bioactive molecules from the microbial world — honed through millennia of evolution — for new drug leads. These small molecules could lead to new antibiotics, immunosuppressant drugs and treatments for high cholesterol, for example.

For four years, Kelleher has collaborated with Nancy P. Keller, the Robert L. Metzenberg and Kenneth B. Raper Professor of Mycology at Wisconsin, and colleagues at Intact Genomics in St. Louis on developing the technology, called FAC-MS (Fungal Artificial Chromosomes with Metabolomic Scoring).

In recent work, the researchers applied their refined method to three diverse fungal species and discovered 17 new natural products from the 56 gene clusters they screened with the new process. That’s a hit rate of 30 percent, which, Kelleher says, is “absolutely phenomenal.”

The study was published June 12 by the journal Nature Chemical Biology. Kelleher, Keller and Chengcang C. Wu of Intact Genomics are the corresponding authors of the paper.

Scientists using fungal species for drug discovery have recently faced a number of problems: the slow rate at which researchers can systematically unlock fungal compounds; the rediscovery of old compounds, such as penicillin; the difference between what a fungus could produce versus what it actually does; and the ability to know when you have a new chemical as opposed to the thousands of more mundane compounds cells produce.


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