Microbes are double-edged swords — they can harm us, but they also carry the cure for disease. The most famous fungal-based pharmaceutical, penicillin, revolutionized medicine. Now, researchers are digging even deeper — quite literally — in the search for new treatments. Their latest source? A fungus that once haunted ancient tombs, and brought an all-too-real curse upon those explorers and archaeologists intrepid and foolhardy enough to venture into those sacred burial sites.
Aspergillus flavus, a mold known for surviving in sealed burial chambers for thousands of years before endangering archaeologists and their crews, has now been found to contain a compound with the potential to do quite the opposite — defying death by its unexpected ability to fight cancer.
A new study led by the University of Pennsylvania’s School of Engineering and Applied Science, published in Nature Chemical Biology, reveals that with a small chemical tweak, a substance made by this fungus can even compete with FDA-approved leukemia drugs.
Ancient Tomb Danger
Aspergillus flavus has a deadly reputation. Known both as a common crop mold and a lurking danger in ancient tombs, its spores have been linked to mysterious deaths — from King Tutankhamun’s 1920s excavation to a 1970s Polish royal tomb incident that apparently killed several archaeologists. The fungus produces toxins and can cause serious respiratory infections, particularly in people with weakened immune systems.
But now, scientists are flipping the script. The compound under investigation belongs to a group called RiPPs, which are peptides made by ribosomes (cell organelles essential for protein production) and later chemically altered to enhance their function.
Many RiPPs have been found in bacteria, but fungi remained mostly overlooked — often misidentified or poorly understood. That’s changing.
To hunt for promising fungal RiPPs, the team screened a dozen Aspergillus species, looking for chemical clues. A. flavus stood out. “The synthesis of these compounds is complicated,” said study lead author Qiuyue Nie in a press release. “But that’s also what gives them this remarkable bioactivity.”
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Fighting Cancer Cells
By disabling certain genes in A. flavus, the team pinpointed the exact protein responsible. They purified four previously unknown molecules with complex, interlocking ring structures, naming them asperigimycins.
When mixed with human cancer cells, two of these compounds showed strong activity against leukemia. A third, initially inactive, was chemically modified with lipid chains to boost its performance and ended up performing as well as traditional chemotherapy drugs like cytarabine and daunorubicin.
Further tests suggest asperigimycins interfere with cancer cell division. “Cancer cells divide uncontrollably,” explained senior author Sherry Gao in the news release. “These compounds block the formation of microtubules, which are essential for cell division.”
Developing Safer Cancer Treatments
Importantly, the molecules showed little to no effect on other cancer types, such as breast, liver, or lung cancer cells, as well as on other bacteria and fungi, hinting at a rare level of specificity. That kind of targeted effect is key for developing safer treatments.
The researchers also identified similar gene clusters in other fungi, hoping there could be many more fungal RiPPs waiting to be discovered.
“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.”
Next up for this fatal fungus-turned-friend: animal testing and, hopefully, human clinical trials. “Nature has given us this incredible pharmacy,” said Gao. “It’s up to us to uncover its secrets. As engineers, we’re excited to keep exploring, learning from nature, and using that knowledge to design better solutions. These results show that many more medicines derived from natural products remain to be found.”
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
Nature Chemical Biology: A class of benzofuranoindoline-bearing heptacyclic fungal RiPPs with anticancer activities
Phys.org: Engineers turn toxic ancient tomb fungus into anti-cancer drug
Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
