Fungus linked to the infamous 'curse' of Tutankhamun potentially holds life-saving properties
Fungus Derived Compounds Show Promise Against Leukemia
A new class of compounds called asperigimycins, derived from the toxic fungus Aspergillus flavus, have demonstrated strong activity against human leukemia cells. These compounds, which have the potential to rival current chemotherapy drugs, were discovered by a team of researchers led by Dr. Gao.
The fungus Aspergillus flavus has a sinister history, having been linked to the 'pharaoh's curse' after archaeologists opened King Tutankhamun's tomb in the 1920s. However, recent research has harnessed this fungus' previously unknown bioactive molecules to develop promising anti-leukemia compounds.
Aspergillus flavus produces a type of molecule known as a RiPP (ribosomally synthesized and post-translationally modified peptide). Gao's team isolated four RiPPs with a distinctive ring-shaped structure from the fungus, and two were found to be highly effective against leukaemia. Two of these compounds, named asperigimycins, showed strong anti-cancer activity.
One of the asperigimycins variants performed as well as two FDA-approved drugs at killing off cancerous cells. Gao stated that modification of the RiPP compound improved its ability to enter the cell, with the addition of a lipid chain enhancing its effectiveness. This modification allows the compound to enter leukemia cells through a transporter protein called SLC46A3, leading to effective killing of the cancer cells.
Of the four identified asperigimycin variants (A-D), C and D possess a pyroglutamate chemical modification associated with anticancer activity, while A and B are inactive. This insight helps understand the structural features crucial for their bioactivity.
The study, published in Nature Chemical Biology, reveals that Aspergillus flavus produces previously unknown molecules. Gao mentioned that the team is planning to create a platform to discover more potentially useful products from fungi, with 95% of these potential products being unknown to science.
More research is needed to understand how RiPPs target cancer cells and why they are effective against leukaemia cells but not other types of cancer cells tested. The discovery highlights fungi as an underexplored reservoir of natural products with medicinal potential, encouraging further research and development.
A third artificially modified RiPP with a lipid chain worked as well as cytarabine and daunorubicin, standard chemotherapy agents. The historical context of the fungus Aspergillus flavus and its link to fatal infections in the past makes the recent discovery of its potential medicinal benefits all the more intriguing. Gao referred to fungi as a "incredible pharmacy" with secrets yet to be uncovered.
1) The study, published in Nature Chemical Biology, indicates that the fungus Aspergillus flavus produces previously unknown molecules that show strong activity against human leukemia cells, potentially rivaling current chemotherapy drugs.
2) Gao's team discovered four RiPPs (ribosomally synthesized and post-translationally modified peptides) with a distinctive ring-shaped structure from the fungus Aspergillus flavus, and two were found to be highly effective against leukemia.
3) One of the asperigimycins variants performed as well as two FDA-approved drugs at killing off cancerous cells, and this reveals its potential as a promising treatment for certain medical-conditions like cancer.
4) The team is planning to create a platform to discover more potentially useful products from fungi, as 95% of these potential products are unknown to science, suggesting a vast untapped resource in the field of health-and-wellness and medical-conditions research.
