Researchers led by the University of Pennsylvania have turned the deadly fungus Aspergillus flavus, linked to the curse of the pharaohs, into a powerful cancer-fighting compound that opens new avenues in the discovery of more fungal drugs.

After archaeologists opened the tomb of King Tutankhamun in the 1920s, a series of untimely deaths among the excavation team fueled rumors of a pharaoh’s curse. Decades later, doctors theorized that fungal spores, dormant for millennia, could have played a role.

In the 1970s, a dozen scientists entered the tomb of Kazimir IV in Poland. Within weeks, ten of them died. Subsequent investigations revealed that the tomb contained Aspergillus flavus, whose toxins can lead to lung infections, especially in people with weakened immune systems.

Now, this same fungus is the source of a promising new cancer treatment.

“The fungi gave us penicillin. These results show that many more drugs derived from natural products remain to be found,” says Sherry Gao, associate professor of chemical and biomolecular engineering and industrial engineering and senior author of the paper in Nature Chemical Biology.

The therapy in question is a class of ribosomally synthesized and post-translationally modified peptides (RiPPs). While thousands of RiPPs have been identified in bacteria, only a few have been found in fungi. To find more RiPPs from fungi, the researchers first studied twelve strains of Aspergillus, which previous research had suggested may contain more of these chemicals, and found that Aspergillus flavus was promising for further study.

After purifying four different RiPPs, the researchers found that the molecules shared a unique structure of interlocking rings. The researchers named these molecules, which had never been described before, after the fungus in which they were found: aspergimicins.

Even without modification, when mixed with human cancer cells, the aspergimicins had medical potential: two of the four variants had potent effects against leukemia cells. Another variant, to which the researchers added a lipid or fatty molecule, also found in the royal jelly that feeds growing bees, worked as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used for decades to treat leukemia.

Through further experimentation, the researchers found that the aspergimicins probably disrupt the process of cell division.

Notably, the compounds had little to no effect on breast, liver or lung cancer cells, suggesting that the effects of aspergimicins are specific to certain cell types, a critical feature for any future drug treatment.

The researchers identified similar groups of genes in other fungi, suggesting that more fungal RiPPS remain to be discovered.

The next step is to test the aspergimicins in animal models, with the hope of one day moving on to clinical trials in humans.