Linked to the infamous
Tutankhamun's curse, the deadly spores can now be turned into a powerful treatment for leukemia.
Microbes have a dual nature: they can cause harm, but they are also a source of cures for disease. The most famous fungus-based drug, penicillin, revolutionized medicine.
Now researchers are digging even deeper - literally - in search of new treatments. What's their latest source? A fungus that once haunted ancient tombs and possessed a real curse for those explorers and archaeologists brave and reckless enough to venture into these sacred burial sites.
Aspergillus yellow (Aspergillus flavus), a mold known for surviving in sealed burial chambers for thousands of years before endangering archaeologists and their teams, has now been found to contain a compound capable of doing the exact opposite - resisting death through its unexpected ability to fight cancer.
A new study conducted by the University of Pennsylvania School of Engineering and Applied Sciences and published in Nature Chemical Biology shows that with a little chemical modification, the substance produced by this fungus could even compete with FDA-approved leukemia drugs.
The dangers of ancient tombs
Aspergillus flavus has a deadly reputation. It is known as a common mold on crops and a hidden danger in ancient tombs, and its spores have been linked to mysterious deaths, from the excavation of Tutankhamun's tomb in the 1920s to an incident in a Polish royal tomb in the 1970s that apparently killed several archaeologists.
The fungus produces toxins and can cause serious respiratory infections, especially in immunocompromised people. But now scientists are changing the scenario.
The Aspergillus yellow compound under study belongs to the RiPPs group, which are peptides produced by ribosomes (cell organelles necessary for protein production) and subsequently chemically modified to enhance their function.
Many RiPPs have been found in bacteria, but fungi have gone largely undetected - they were often misidentified or poorly understood. But this situation is changing. In their search for promising RiPP compounds found in fungi, the team screened a dozen Aspergillus species, looking for chemical clues.
Aspergillus flavus stood out among the rest. "The synthesis of these compounds is complex," said the study's lead author Qiyue Ni. "But this is what gives them such remarkable biological activity."
Fighting cancer cells
By switching off certain genes in Aspergillus flavus, the team pinpointed the responsible protein. They purified four previously unknown molecules with complex, interconnected ring structures and named them aspergimycins.
When mixed with human cancer cells, two of these compounds demonstrated strong activity against leukemia. The third, initially inactive, was chemically modified using lipid chains to enhance its efficacy and eventually demonstrated similar efficacy to traditional chemotherapy drugs such as cytarabine and daunorubicin.
Photo: hi-tech.mail.ru
Further tests show that aspergimycins prevent cancer cells from dividing. "Cancer cells divide uncontrollably," explains senior author Sherry Gao in a press release. "These compounds block the formation of microtubules, which are essential for cell division."
Developing safer cancer treatments
Importantly, these molecules had virtually no effect on other types of cancer, such as breast, liver or lung cancer, as well as other bacteria and fungi, indicating a rare level of specificity. This targeted effect is key to developing safer therapies.
The researchers also identified similar gene clusters in other fungi, hoping that there are many more RiPPs contained within them waiting to be discovered. "Although only a few have been found, almost all of them have strong biological activity," says Ni. "This is an unexplored area with great potential."
The next step for this deadly fungus turned helper will be animal testing and, it is hoped, further human clinical trials. "Nature has given us this incredible pharmacy," says Gao. "We only have to unlock its secrets. As engineers, we are passionate about continuing to explore, learn from nature, and use this knowledge to develop better solutions. These results show that many drugs derived from natural materials are yet to be discovered."