Could an ancient killer be the key to curing cancer? Penn engineers have turned a notorious, toxic fungus—once blamed for mysterious deaths—into a promising new leukemia drug, unlocking nature’s hidden pharmacy for the next generation of cancer therapies.
Key Points at a Glance
- Researchers isolated a new class of cancer-fighting compounds, asperigimycins, from the toxic fungus Aspergillus flavus.
- The compounds, called RiPPs, show powerful effects against leukemia cells—sometimes matching or beating FDA-approved drugs.
- Adding natural lipids to asperigimycins boosted their ability to enter cancer cells, thanks to a gene called SLC46A3.
- The study reveals an untapped world of fungal medicines, suggesting many more life-saving drugs remain to be found.
The same fungus that once haunted ancient tombs with deadly spores is now giving hope to cancer patients. In a breakthrough led by the University of Pennsylvania and published in Nature Chemical Biology, scientists have discovered how to extract and enhance molecules from Aspergillus flavus—the toxic microbe infamously linked to mysterious deaths in Egyptian and Polish burial sites. The result? A new family of anti-cancer drugs with remarkable precision and power.
The story starts with the search for new medicines in the most unlikely places. “Fungi gave us penicillin,” notes lead researcher Sherry Gao. “Now, we’re finding that their pharmacy is much bigger than anyone imagined.”
The molecules at the heart of the study are called RiPPs—ribosomally synthesized and post-translationally modified peptides. Unlike most known RiPPs, which are made by bacteria, these newly found versions come from fungi, making their discovery even more extraordinary. After purifying four variants, the team found two that hit leukemia cells hard, while a third became even more potent when the scientists added a lipid—a trick borrowed from bee royal jelly.
This added fat helped the compounds enter cancer cells more efficiently, thanks to a gene (SLC46A3) that acts as a molecular gateway. It’s a finding that could unlock new ways to deliver medicines precisely where they’re needed, not just for cancer but potentially for other diseases, too.
Importantly, the asperigimycins left healthy cells and bacteria untouched, a critical feature for any future cancer therapy. Instead of causing widespread damage, these molecules seem tuned to target only the cells researchers want to stop—offering hope for safer, more selective treatments.
The path to these new medicines was anything but simple. The team used advanced genetic and chemical analysis to pinpoint the fungal genes responsible, then “switched them off” to prove their connection. This combined approach could help scientists find many more fungal RiPPs hiding in nature, with new medicinal powers waiting to be discovered.
With nearly two dozen cyclic peptides already approved for clinical use since 2000, and this new discovery showing even more promise, the future of fungal drug research looks brighter than ever. “Nature has given us this incredible pharmacy,” says Gao. “It’s up to us to keep exploring.”
Source: University of Pennsylvania School of Engineering and Applied Science
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