Toxic fungus of the Pharaohs’ curse is turned into an anti-leukaemia drug
A team of researchers from the University of Pennsylvania has repurposed the lethal fungus Aspergillus flavus, historically associated with the infamous curse of the pharaohs, into a potent cancer-fighting agent. This breakthrough paves the way for further exploration into fungal-based medications.
The curse of the pharaohs came into public consciousness after the opening of King Tutankhamun’s tomb in the 1920s, when several members of the excavation team died unexpectedly. Years later, medical experts proposed that dormant fungal spores could have been a factor.
In the 1970s, another incident occurred when a group of scientists explored the tomb of Casimir IV in Poland. Within weeks, ten out of the twelve researchers had died. Follow-up investigations revealed the presence of Aspergillus flavus, a fungus capable of producing toxins that can cause lung infections, particularly in individuals with compromised immune systems.
Interestingly, this very fungus is now at the heart of an innovative cancer treatment.
“Fungi have already provided us with penicillin. These findings indicate that there are still many undiscovered drugs derived from natural products,” states Sherry Gao, Associate Professor of Chemical and Biomolecular Engineering and Manufacturing, and the senior author of the published paper in Nature Chemical Biology.
The New Cancer Treatment
The treatment under investigation involves a category of ribosomally synthesized and post-translationally modified peptides (RiPPs). Although thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. To discover more fungal RiPPs, the researchers initially studied twelve strains of Aspergillus, which earlier research had suggested might contain more of these compounds. They found Aspergillus flavus to be a promising candidate for further research.
After isolating four distinct RiPPs, the team discovered that these molecules had a unique structure comprising interlocking rings. These previously unidentified molecules were named after the fungus from which they were derived: aspergimicins.
Even in their unmodified state, the aspergimicins demonstrated medical potential when combined with human cancer cells. Two of the four variants exhibited strong effects against leukemia cells. Another variant, enhanced with a lipid or fatty molecule also found in royal jelly, the sustenance for growing bees, was as effective as cytarabine and daunorubicin, two FDA-approved drugs used for leukemia treatment for several decades.
Further experimentation revealed that aspergimicins likely interfere with the process of cell division.
Interestingly, the compounds had minimal to no impact on breast, liver, or lung cancer cells, suggesting that aspergimicins’ effects are specific to certain cell types—an essential characteristic for any future drug treatment.
The researchers also identified similar gene clusters in other fungi, implying that more fungal RiPPs await discovery.
The following phase involves testing the aspergimicins in animal models, in anticipation of potentially progressing to clinical trials in humans.
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