Biotechnologists learned to turn toxic tomb fungus into anti-tumor drugs
Researchers at the University of Pennsylvania have transformed the toxic fungus Aspergillus flavus into a potent cancer-fighting compound that destroys tumors. The discovery of aspergimycins, a class of RiPP molecules, demonstrates significant potential in treating leukemia.
Researchers led by the University of Pennsylvania have transformed a deadly fungus into a potent cancer-fighting compound. The promising oncology tumor-destroying compound rivals medications approved by the U.S. Food and Drug Administration (FDA) and opens new horizons in the discovery of new fungal medicines. This is reported by UNN with reference to Phys.
After isolating a new class of molecules from Aspergillus flavus, a toxic fungus associated with deaths during ancient tomb excavations, researchers modified the chemicals and tested them against leukemia cells.
Fungi have played and continue to play an important role in the life of the planet and humankind, says Sherri Gao, associate professor of Chemical and Biomolecular Engineering (CBE) and Bioengineering (BE) at the President's College of the University of Pennsylvania, and senior author of a new paper in Nature Chemical Biology on this scientific work. Fungi gave us penicillin. These results show that many more medicines derived from natural products are still to be found - she said.
Aspergillus flavus, named for its yellow spores, has long been a villainous microorganism. After archaeologists opened Tutankhamun's tomb in the 1920s, a series of premature deaths among the excavation team fueled rumors of a "pharaoh's curse." Decades later, doctors theorized that fungal spores, dormant for millennia, may have played a role in a series of mysterious deaths. In the 1970s, a dozen scientists entered the tomb of Casimir IV in Poland. Within a few weeks, 10 of them died. Later investigations showed that the tomb contained A. flavus, whose toxins can lead to lung infections, especially in people with weakened immune systems.
Now this fungus is a confirmed source of a promising new cancer therapy. It is about a therapy that is a class of ribosome-synthesized and post-translationally modified peptides or RiPPs. The name refers to the way the compound is produced - by a ribosome, a tiny cellular structure that produces proteins - and the fact that it is later modified, in this case, to enhance its cancer-killing properties.
Purifying these chemicals is a difficult task. Although thousands of RiPPs have been identified in bacteria, only a few have been found in fungi. This is partly because previous researchers mistakenly identified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi create these molecules - says CBE postdoctoral fellow and first author of the article Quyue Nian. The synthesis of these compounds is complex, adds Nian. But that's what gives them such excellent bioactivity.
After purifying four different RiPPs, the researchers found that the molecules had a unique interlocked ring structure. The scientists named these molecules, which had never been described before, after the fungus in which they were found: aspergimycins. Even without modification, when mixed with human cancer cells, aspergimycins demonstrated medical potential: two of the four variants had a powerful effect against leukemic cells.
Another variant, to which researchers added a lipid, or fatty molecule, also found in royal jelly that feeds developing bees, worked as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used to treat leukemia for decades.
In addition to demonstrating the medical potential of aspergimycins, the researchers found similar gene clusters in other fungi. This indicates that there is a prospect of discovering more fungal RiPPs and their beneficial properties.
