Researchers at the University of Pennsylvania have transformed a toxic fungus once linked to deaths in ancient tombs into an anti-cancer drug. The team discovered powerful compounds hidden within Aspergillus flavus, a mold long known for its deadly effects, and successfully modified it to attack leukemia cells.
The breakthrough highlights how a toxic fungus could lead to a new anti-cancer drug, and opens the door to future treatments derived from natural sources.
The study, published in Nature Chemical Biology, revealed that molecules isolated from A. flavus—a fungus notorious for producing harmful spores—can be turned into potent compounds that rival existing cancer drugs.
The researchers altered the structure of these natural substances in the lab and found they were highly effective against certain leukemia cells. In some cases, their performance matched that of FDA-approved treatments.
The fungus at the center of the study has a notorious history. After the opening of King Tutankhamun’s tomb in the 1920s, several archaeologists died under mysterious circumstances. Later, scientists suspected dormant fungal spores could have played a role.
A similar pattern emerged in the 1970s when ten out of twelve researchers died shortly after entering the tomb of Polish king Casimir IV. Investigations later found A. flavus in both tombs.
From ancient tombs to fighting cancer! Researchers have found a powerful cancer-killing compound in a deadly fungus. Here’s a quick thread:
A deadly tomb fungus (Aspergillus flavus) linked to ancient tomb deaths & a “pharaoh’s curse” rumor is now a source for cancer-killing… pic.twitter.com/xAEuRcSj3d
— Arunachalam B (@AI_Techie_Arun) June 23, 2025
Despite its dangers, A. flavus has now emerged as a surprising source of hope. Researchers identified a class of small, ring-shaped molecules from the fungus known as RiPPs—natural compounds made by cells and modified to boost their effects. Although thousands of RiPPs have been found in bacteria, they are rare in fungi due to past confusion over their origins.
The team employed a novel approach, integrating genetic analysis and chemical screening to identify the source of the RiPPs in A. flavus. By deactivating specific genes associated with a particular protein, they observed the disappearance of chemical signals, thus confirming the connection. They have named the newly discovered compounds “asperigimycins.”
When tested, two asperigimycins effectively killed leukemia cells. A modified version, enhanced with a fatty molecule found in royal jelly, performed as well as long-standing cancer drugs like cytarabine and daunorubicin.
Researchers also found that a gene called SLC46A3 played a key role in helping asperigimycins enter cancer cells. The gene acts like a gateway that moves materials out of internal cell compartments. Understanding how this gateway works could enhance the delivery of other drugs—particularly similar ring-shaped molecules—into cells.
Additional tests showed that asperigimycins mainly target leukemia cells, leaving other cancer types, bacteria, and fungi largely unaffected. This selectivity makes them strong candidates for future therapies with fewer side effects.
