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Genome mining uncovers how a fungus makes a chemical agent against others of its kind.

The key to creating new antifungal drugs might be hiding in the genomes of fungi that need to protect themselves from their own chemical weapons.

To defend itself against other fungi, Penicillium restrictum makes a molecule called restricticin, which blocks a crucial fungal enzyme. Shutting down the enzyme can curb the growth of fungi, such as Candida albicans, that infect humans.

How P. restrictum makes restricticin has been unknown, but Yi Tang at the University of California, Los Angeles, and his colleagues realized that any fungus that makes restricticin would also need to protect itself from its own poison. They suspected that the fungal genes that encode restricticin might sit close to genes for a restricticin-resistant version of its target enzyme.

The researchers built a genome-mining algorithm to look for genes encoding a resistant enzyme near clusters of genes that could potentially make restricticin. The algorithm led to the discovery of the biosynthetic pathway for restricticin — and showed that the compound is also produced by other species of fungus. The authors hope that their genome-mining method will lead to the identification of other naturally occurring antifungal substances.

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