New research from Penn Engineering has uncovered the catalyst that creates a compound in fungi whose derivatives are applied to treatments for cancer and inflammation.
Fungi are a goldmine for medicines, but the process by which fungi synthesize some of their most potent compounds remains opaque. This is especially true of cyclopentachromone, a key building block in fungal products whose derivatives have shown promise in fighting cancer and reducing inflammation, among other medicinal properties.
Qiuyue Nie and Maria Zotova at work in the lab, in a room designed for culturing fungi.
(Image: Bella Ciervo)
While chemists have made progress in creating chromone derivatives in the lab, the molecule’s distinctive structure has proven difficult to precisely and reliably copy. “It’s very easy to wind up with a version where the chemical bonds aren’t in the right place, or the structure is flipped,” says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering and in Bioengineering.
In a new paper in the Journal of the American Chemical Society, members of the Gao Lab describe how they deciphered nature’s own instructions—namely, the genes of Penicillium citrinum, a mold commonly found on citrus fruits—to discover a previously unreported enzyme that catalyzes the creation of cyclopentachromone-containing compounds.
Part of what makes cyclopentachromone unique is its distinctive structure, which includes a trio of carbon rings, two with six carbons, and one with five carbons. Like the scaffold used to erect a building, this series of rings provides the structural foundation for numerous bioactive molecules. The researchers were able to source the chemical precursor to developing the different ring structure. The researchers hope that future work will walk this newly discovered pathway using the genetic map that guides it to further advance the use of fungal compounds in medicine.
“Nature has had billions of years to develop pathways for creating these compounds,” says Gao, the paper’s senior author. “Now we can borrow nature’s tools to develop and study these compounds further, which could potentially lead to the development of new pharmaceuticals.”
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