Latest news with #RiPPs
Gizmodo
29-06-2025
- Science
- Gizmodo
Notorious Fungus Blamed for ‘Mummy's Curse' Is Now a Promising Cancer Treatment
In the 1920s, a number of workers on the excavation team that uncovered King Tutankhamun's tomb met untimely deaths. Five decades later, 10 out of 12 scientists died after entering the tomb of the 15th-century Polish King Casimir IV. In both cases, researchers suggested that fungal spores could have played a role in the mysterious deaths, specifically identifying the fungus Aspergillus flavus within the Polish burial. A. flavus is now making a comeback, but not as a reawakened killer from ancient tombs, but instead as a surprisingly effective cancer-fighting compound. By modifying a newly identified molecule found in the fungus, the researchers created a compound that performed as effectively against leukemia cells as FDA-approved drugs. The molecules at the center of these anti-cancer properties, known as ribosomally synthesized and post-translationally modified peptides, or RiPPs, are a diverse group of natural molecules assembled by the ribosome (which makes proteins) and later modified by enzymes. They conduct many different biological activities, some of which are already known for their anti-cancer properties. To date, researchers have identified only a handful of RiPPs in fungi—which is significantly less than the thousands previously discovered in bacteria. Part of the problem is that scientists didn't fully understand how fungi create RiPPs. 'The synthesis of these compounds is complicated,' Qiuyue Nie, a postdoctoral fellow at the University of Pennsylvania's Department of Chemical and Biomolecular Engineering, said in a university statement. 'But that's also what gives them this remarkable bioactivity.' Genetic analysis suggested that a specific A. flavus protein could be a source of fungal RiPPs. Sure enough, when Nie and her colleagues turned off the genes responsible for said protein, RiPPs' chemical markers also vanished. Using this approach, the team discovered four different A. flavus RiPPs with a previously undocumented structure of interlocking rings. After researchers purified these RiPPs, which they named asperigimycins, two of the four unique molecules performed well against human leukemia cells without further modifications. When mixed with a lipid (a fatty molecule), a separate RiPPs variant performed as well as cytarabine and daunorubicin, both of which are long-established FDA-approved leukemia drugs. To investigate this lipid's enhancement properties, the researchers went back to turning genes off and on. In this way, they identified a gene associated with the process that lets enough asperigimycins into the cancer cells. 'This gene acts like a gateway,' said Nie, the first author of the study published Monday in Nature Chemical Biology. 'It doesn't just help asperigimycins get into cells, it may also enable other 'cyclic peptides' to do the same.' Cyclic peptides are other chemicals with known medicinal properties. 'Knowing that lipids can affect how this gene transports chemicals into cells gives us another tool for drug development,' Nie added. The researchers also discovered that asperigimycins might disrupt the process of cell division—which is good news for cancer treatment, since cancer consists of uncontrolled cell division. Furthermore, the compounds had little to no effect on breast, liver, or lung cancer cells, as well as on a number of bacteria and fungi. While this might sound like a negative thing, asperigimycins' potentially targeted impact would be an important characteristic for future medications. Moving forward, the researchers aim to test asperigimycins in animal trials. The recent study investigates a promising new cancer therapy, but it also paves the way for future research into fungal medicines. 'Nature has given us this incredible pharmacy,' said Sherry Gao, senior author of the study and an associate professor also in the University of Pennsylvania's Department of Chemical and Biomolecular Engineering. 'It's up to us to uncover its secrets.'
Daily Mirror
24-06-2025
- Health
- Daily Mirror
'Curse' which killed explorers entering Egyptian tombs could fight cancer
When people died after entering the ancient pyramids for the first time it was blamed on a Pharaoh's Curse or Mummy's Revenge The "Pharaoh's Curse" which killed archaeologists, scientists and explorers who broke into the tombs of ancient kings in Egypt has been transformed into an anti-cancer drug. After archaeologists opened King Tutankhamun's tomb in the 1920s, a series of untimely deaths among the excavation team fuelled rumours of a "pharaoh's curse". A dozen scientists entered the tomb of Casimir IV in Poland In the 1970s but, within weeks, 10 of them died. Decades later, doctors theorised that fungal spores, dormant for millennia, could have played a role. Scientists isolated a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to infamous deaths following the excavations of ancient tombs. Later investigations revealed the tomb contained A. flavus, whose toxins can lead to lung infections, especially in people with compromised immune systems. Now, that same fungus is the unlikely source of a promising new cancer therapy. American scientists modified the chemicals they isolated from A. flavus and tested them against leukaemia cells. Their findings, published in the journal Nature Chemical Biology, showed a "promising" cancer-killing compound that rivals already-approved drugs - and opens new frontiers for fungal medicines. Study senior author Professor Sherry Gao, of the University of Pennsylvania, said: 'Fungi gave us penicillin. 'These results show that many more medicines derived from natural products remain to be found.' She explained that the therapy in question is a class of ribosomally synthesised and post-translationally modified peptides, or RiPPs. The name refers to how the compound is produced - by the ribosome, a tiny cellular structure that makes proteins - and the fact that it is modified later to enhance its cancer-killing properties. Study first author Dr Qiuyue Nie said: 'Purifying these chemicals is difficult." She says that while thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. Dr Nie said that is because researchers previously misidentified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi created the molecules. She added: 'The synthesis of these compounds is complicated. But that's also what gives them this remarkable bioactivity.' To find more fungal RiPPs, the research team first scanned a dozen strains of Aspergillus, which previous research suggested might contain more of the chemicals. By comparing chemicals produced by these strains with known RiPP building blocks, the researchers identified A. flavus as a "promising" candidate for further study. Genetic analysis pointed to a particular protein in A. flavus as a source of fungal RiPPs. When the researchers turned the genes that create that protein off, the chemical markers indicating the presence of RiPPs also disappeared. They said the new approach - combining metabolic and genetic information - not only pinpointed the source of fungal RiPPs in A. flavus, but could also be used to find more fungal RiPPs in the future. Further experiments suggested that asperigimycins likely disrupt the process of cell division. Prof Gao said: 'Cancer cells divide uncontrollably. These compounds block the formation of microtubules, which are essential for cell division.' She says the compounds had little to no effect on breast, liver or lung cancer cells - or a range of bacteria and fungi - suggesting that asperigimycins' disruptive effects are specific to certain types of cells, a critical feature for any future medication. As well as showing the medical potential of asperigimycins, the research team also identified similar clusters of genes in other fungi, suggesting that more fungal RiPPS remain to be discovered. Dr Nie said: 'Even though only a few have been found, almost all of them have strong bioactivity. This is an unexplored region with tremendous potential.' The researchers say the next step is to test asperigimycins in animal models, with the hope of one day moving to human clinical trials. Prof Gao added: 'Nature has given us this incredible pharmacy. 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.'
