A little over 100 years ago, King Tutankhamun’s tomb was opened in Egypt, releasing rumors of a curse. Today, researchers have harnessed the source of that “curse” into a cancer-fighting compound.
As it turns out, the curse of King Tut’s tomb wasn’t actually paranormal. It was Aspergillus flavus, a toxic crop fungus that also caused 10 out of a dozen scientists who entered the tomb of Casimir IV in Poland to die within weeks of opening the tomb in the 1970s.
“Sherlock Holmes” author Sir Arthur Conan Doyle did once suggest that Egyptian priests left the lethal yellow spores to punish grave robbers, according to the University of Texas Medical Branch at Austin. That theory hasn’t been proven, but researchers at Penn’s School of Engineering and Applied Science have shown that the deadly fungus can also be a life-saver.
Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in Bioengineering (BE) and senior author of research on the subject recently published in Nature Chemical Biology, noted that fungus has already been used to make a life-saving medicine, the antibiotic penicillin. To study the potential uses of Aspergillus fungi, her team scanned a dozen strains and found that A. flavus was a candidate for further study.
In particular, the researchers were looking for a class of ribosomally synthesized and post-translationally modified peptides, or RiPPs. These are short strings of amino acids made in the ribosome cellular structure that makes proteins that are then modified later to enhance certain properties.
“Genetic analysis pointed to a particular protein in A. flavus as a source of fungal RiPPs,” explained Penn Engineering Today. “When the researchers turned the genes that create that protein off, the chemical markers indicating the presence of RiPPs also disappeared.”
Qiuyue Nie, a postdoctoral fellow in CBE and the paper’s first author, said the synthesis of RiPPs in fungi is different and more complicated than in bacteria.
“That’s also what gives them this remarkable bioactivity,” Nie added.
Researchers found the molecules shared a unique structure of interlocking rings after purifying four different RiPPs from the fungus. They named these asperigimycins. According to Penn Engineering Today, two of the four variants had potent effects against leukemia cells without any modification.
“Another variant, to which the researchers added a lipid, or fatty molecule, that is also found in the royal jelly that nourishes developing bees, performed as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used for decades to treat leukemia,” said Penn Engineering Today.
Leukemia is a cancer of early blood-forming cells, often of white blood cells, per the American Cancer Society. National Cancer Institute data indicates that 536,245 people in the U.S. were living with leukemia as of 2022 and approximately 1.5% of people will be diagnosed with the disease at some point int their lifetime. Last year, there were nearly 67,000 new cases in the U.S. and more than 23,500 deaths from the cancer.
After the RiPP discoveries, the team conducted further experimentation and found that asperigimycins likely disrupts the process of cell division. Cancers such as leukemia are characterized by cells that divide uncontrollably.
“These compounds block the formation of microtubules, which are essential for cell division,” Gao explained of the A. flavus-derived compounds.
Penn Today described the compound as one that “rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines.”
For readers who want to know more about fungus, Audacy’s “Something Offbeat” has covered the “zombie fungus” featured in the HBO show “The Last of Us”. Just this week, the show also covered the growing field research into magic mushrooms.