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A fungus once feared as the source of the so-called “Pharaoh’s Curse” has been transformed into a potential treatment for leukemia, according to researchers at the University of Pennsylvania.
The fungus, Aspergillus flavus, has long been associated with mysterious deaths linked to ancient tombs. After the discovery of King Tutankhamun’s tomb in the 1920s, several members of the excavation team died under unexplained circumstances, giving rise to rumors of a curse. In later decades, experts speculated that dormant fungal spores, possibly thousands of years old, might have contributed to the deaths.
In another case in the 1970s, 12 scientists entered the tomb of 15th-century Polish king Casimir IV. Ten died within weeks. Investigators later detected Aspergillus flavus, which produces toxins known to cause severe lung infections, especially in people with weakened immune systems.
Now, scientists have found a way to harness the deadly fungus to fight cancer.
“Fungi gave us penicillin. These results show that many more drugs derived from natural products remain to be discovered,” said Xue Sherry Gao, associate professor of chemical and biomolecular engineering at Penn and senior author of the study published in Nature Chemical Biology.
The new treatment is based on a class of molecules called RiPPs: ribosomally synthesized and post-translationally modified peptides. While common in bacteria, RiPPs have rarely been identified in fungi. Researchers focused on 12 strains of Aspergillus, narrowing in on A. flavus as the most promising.
The team isolated four previously unknown RiPPs, which shared a unique ring-shaped structure. They named the molecules aspergilimicins, after the fungus in which they were found.
When tested against human cancer cells, two of the aspergilimicins showed strong activity against leukemia. A third, modified with a lipid molecule found in royal jelly, the substance that feeds developing honeybee queens, was as effective as cytarabine and daunorubicin, two standard chemotherapy drugs.
The compounds appear to disrupt cell division, the researchers said. They had little to no impact on breast, liver or lung cancer cells, suggesting the molecules may selectively target certain types of cancer, an important feature for drug development.
The researchers also identified similar gene clusters in other fungi, raising the possibility that many more fungal RiPPs are waiting to be discovered.
Next, the team plans to test the aspergilimicins in animal models, with the goal of advancing to human clinical trials.
