Nearly a century ago, rumors of a deadly curse swirled around the team that unearthed King Tutankhamun’s resting place. One by one, archaeologists who entered the tomb fell ill or died under mysterious circumstances. Decades later, a similar fate met a group of Polish researchers excavating the crypt of King Casimir IV. Ten out of twelve scientists perished soon after exposure.
At the time, some cooler heads speculated that toxic mold may have been to blame. Eventually, this was confirmed. Now, scientists have gone back to that same fungus, Aspergillus flavus, not to fear it, but to harness its power.
A new study published in Nature Chemical Biology reveals that this deadly fungus could be the source of a potent cancer treatment. Researchers at the University of Pennsylvania and collaborators around the world have turned one of the most toxic molds known to science into a promising anti-leukemia compound.
“This is nature’s irony at its finest,” said Sherry Gao, senior author of the study and a professor of chemical and biomolecular engineering at UPenn. “The same fungus once feared for bringing death may now help save lives.”
The Cursed Fungus
Aspergillus flavus is a common soil fungus. It produces hardy yellow spores and has been infamous for contaminating crops and causing lung infections, particularly in people with weakened immune systems. But its sinister reputation was cemented by the so-called “pharaoh’s curse.”
When Lord Carnarvon, who funded the King Tut excavation, died months after entering the tomb in 1922, speculation ran wild. Was it superstition—or something biological?
In the 1970s, the deaths of Polish archaeologists entering King Casimir IV’s tomb led to closer scrutiny. Tests found A. flavus in the burial chamber. The fungus, it seemed, could lie dormant for centuries, waiting to release its spores when disturbed.
Now, scientists are taking a second look.
From Killer to Cure
The research team was searching for a class of molecules known as RiPPs—ribosomally synthesized and post-translationally modified peptides. These are small proteins made in cells and chemically tweaked afterward, often by enzymes.
While thousands of RiPPs have been found in bacteria, they’re rarely seen in fungi.
“Purifying these chemicals is difficult,” explained Qiuyue Nie, the study’s first author and a postdoctoral fellow at UPenn. “But that’s also what gives them this remarkable bioactivity.”
The team screened a dozen strains of Aspergillus fungi, comparing their chemical profiles to known RiPP structures. One strain of A. flavus stood out. Genetic analysis pointed to a protein that seemed key to RiPP production. When the researchers turned off the gene responsible for that protein, the RiPP markers vanished.
That led them to a new class of molecules with a complex architecture: interlocking rings built around a benzofuranoindoline core. They named the compounds asperigimycins.
Even in their natural state, some asperigimycins killed leukemia cells in lab tests. But the researchers went further. By attaching a fatty acid—similar to lipids found in royal jelly that feeds queen bees—they supercharged the compound’s cancer-killing power.
In head-to-head tests, the enhanced version, named 2-L6, performed as well as cytarabine and daunorubicin, two drugs that have been the cornerstone of leukemia treatment for decades.
“A derivative with a C-11 linear fatty acid… achieves nanomolar anticancer potency comparable to that of clinically approved antileukemia drugs,” the study notes.
Selective Strike
The researchers also discovered something unexpected: asperigimycins seem to target leukemia cells specifically. They had little to no effect on breast, liver, or lung cancer cells, nor on a range of bacteria and fungi.
That kind of precision is rare and very, very valuable.
“Cancer cells divide uncontrollably,” said Gao. “These compounds block the formation of microtubules, which are essential for cell division.”
By disrupting this process only in leukemia cells, the compounds may offer a way to treat cancer without the broad collateral damage caused by many chemotherapies.
The Hidden Fungal Pharmacy
The discovery of asperigimycins is just the beginning. Using the same methods, researchers have identified similar gene clusters in other fungi.
“Even though only a few have been found, almost all of them have strong bioactivity,” said Nie. “This is an unexplored region with tremendous potential.”
The next step is to test the compounds in animal models. If those trials are successful, the team hopes to begin human clinical trials in the future.
For now, A. flavus remains a danger in food crops and dusty tombs. But it’s also a reminder that nature often hides its best medicines in the unlikeliest places.
“Nature has given us this incredible pharmacy,” said Gao. “It’s up to us to uncover its secrets.”
The study was a global effort, drawing on expertise from the University of Pennsylvania, Rice University, MD Anderson Cancer Center, Washington University in St. Louis, Baylor College of Medicine, the University of Pittsburgh, and the University of Porto. It was funded by the National Institutes of Health, the National Science Foundation, and several foundations and cancer research institutes.
