Scientists have found a way to turn a deadly fungus into a powerful medicine for fighting cancer. The fungus, called Aspergillus flavus, was once feared for causing mysterious deaths after people opened ancient tombs like that of King Tutankhamun. Now, researchers at the University of Pennsylvania have found that this same fungus can produce new compounds that kill leukemia cells.
The study, led by Professor Sherry Gao, has been published in the journal Nature Chemical Biology. It explains how a team of scientists found a new class of molecules called asperigimycins. The researchers took these molecules from the fungus and tested them on human leukemia cells.
The results were exciting. The compounds killed cancer cells effectively, and with a small chemical change, they became even more powerful—performing as well as well-known cancer drugs used for many years.
Scientists know Aspergillus flavus for its toxic yellow-green spores. It grows in soil and old places, and can be very dangerous to people with weak immune systems. Many people believe it was part of the so-called “Pharaoh’s Curse,” which came after several people died suddenly following the opening of King Tut’s tomb in 1922.
Later, a similar case happened in Poland in the 1970s, when scientists exploring another royal tomb became ill, and many died. Medical experts believe the fungus, which had been dormant for centuries, released spores that caused deadly lung infections.
This dark history makes the discovery even more surprising. “Nature has given us this incredible pharmacy. It’s up to us to uncover its secrets,” said Professor Gao.
The researchers were not looking for old legends. Instead, they studied a group of natural compounds called RiPPs. Specifically, RiPPs stand for ribosomally synthesised and post-translationally modified peptides.
Cells make these molecules and then modify them to become stronger. Some RiPPs in bacteria fight disease, but very few RiPPs have been found in fungi. Fungi are hard to isolate.
Qiuyue Nie, the first author of the study, explained, “The synthesis of these compounds is complicated. But that’s also what gives them this remarkable bioactivity.”
The team examined more than a dozen Aspergillus species and discovered that Aspergillus flavus produced unique RiPPs. They named the new molecules asperigimycins. These compounds had a special structure, with rings that locked together. When tested on leukaemia cells, two of the four new compounds were strong enough to kill the cancer cells.
But things got even better when the scientists made a small change to the molecules. They added a lipid—a fatty molecule—to one of the asperigimycins. That change made it just as effective as two popular leukaemia drugs: cytarabine and daunorubicin.
To figure out why the change worked so well, the researchers studied how the molecule entered the cancer cells. They discovered a gene called SLC46A3 that helps aspergimycins enter cells. “SLC46A3 acts like a gateway,” Nie said. “It allows asperigimycins to escape the lysosome—basically, a cellular recycling bin—and get into the cell’s main chamber where they can do their job.”
Once inside, the compound stops the cancer cells from dividing. It does this by blocking microtubules, which are like tiny rods that help cells divide. Without them, the cancer can’t grow.
One of the most exciting things about asperigimycins is that they don’t harm healthy cells. When tested on breast, liver, and lung cancer cells, as well as on bacteria and other fungi, the compounds had little to no effect. This kind of cell-specific activity is very important for the development of new drugs. It means fewer side effects and more targeted treatment.
“This is what you want in a drug,” said Professor Gao. “Precision. Power. And safety.”
Even though asperigimycins are new, the researchers believe this is just the beginning. They have already found similar gene clusters in other fungi. This means scientists could discover many more hidden RiPPs. These discoveries could possibly lead to more antibiotics, antivirals, and cancer drugs in the future.
“Fungi are like a hidden library,” Nie said. “We’ve only just begun to read the first few pages.”
The next step for the team is to test asperigimycins in animals. If those tests are successful, the ultimate goal is to proceed to human clinical trials. It may take years, but this breakthrough has opened a new door in the search for better cancer treatments.
From tombs thought to be cursed, to labs filled with hope, Aspergillus flavus has made an incredible journey—from killer to healer.
