The toxic fungus once thought to have caused a fatal lung infection to grave explorers could hold the key to powerful new cancer treatments, new research suggests.
Within months of the discovery of King Tutan Kamun’s tomb in 1922, the Count, who funded the excavations and visited the “great” burial site, died, leading many to cursed the people who had entered the tomb. In the 1970s, 10 of the 12 archaeologists who excavated the 15th century basement of Poland’s Kashmir IV brought similar fates.
Analysis of Kashmir tombs revealed the presence of a fungus called toxins, known to cause fatal pulmonary infections.
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A new study published in Nature Chemical Biology shows that the same fungus currently has promising treatment for leukemia. The team of researchers identified and designed a class of molecules within a fungus called asperigycin, which kills leukemia cells in laboratory settings.
“This is the best natural irony,” said senior author Shelley Gao, professor of chemistry and biomolecular engineering at the University of Pennsylvania, in a statement. “The same fungus that once feared death could now help save lives.”
Aspergillus flavus produces spores that can rest for centuries, including sealed tombs inside. If disturbed, the fungus can cause fatal respiratory infections, especially in people with weakened immune systems.
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In their new research, scientists have looked at unique compounds produced by fungi and discovered a class of natural compounds called RIPPS (peptides in which ribosomas are synthesized and modified after translation). These molecules are difficult to sequester and rarely found in fungi, but retain therapeutic promises due to their complex structure and biological activity. This means that it has complex and unique shapes that can interact with biological systems in powerful ways, such as killing cancer cells.
Author Qiuyue Nie, a researcher in chemistry and biomolecular engineering at the University of Pennsylvania, “We have found four new asperigine sewing machines with unusual interlocking ring structures,” the statement said. “Two of them had strong antileukemia properties even without modification.”
To increase the effectiveness of the drug, researchers have attached lipid molecules similar to those found in Royal Jelly, a nutrient-rich substance that maintains queen bees. This allowed the drug to enter cancer cells more efficiently, as lipids help the drug to cross the cell membrane.
Further analysis revealed how a gene called SLC46A3 functions as a kind of molecular gateway, helping the drug directly target cell compartments and leukemia cells. This finding could help provide other promising but unruly drugs in the future.
Unlike broad-spectrum chemotherapeutic agents that can damage healthy cells, asperigycin appears to specifically destroy leukemia cell division without affecting healthy tissue. Early testing also suggests that the compounds have minimal effects on breast, liver and lung cancer cells. Researchers say this selectivity is important to minimize unnecessary side effects.
In addition to asperigycin, the team believes similar life-saving compounds may be hidden in other fungal species.
The team plans to test asperigycin in animal models with the ultimate goal of starting human clinical trials. And by scanning the fungal genome and exploring more strains of Aspergillus, they want to unlock new treatments.
“The ancient world still offers tools for modern medicine,” GAO said. “The grave was afraid of a curse, but it could be a source of healing.”
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