In a recent study, researchers at Penn's School of Engineering and Applied Science transformed a toxic fungus known for contaminating crops into a promising "cancer-killing compound" and treatment for leukemia.
The study, published June 23 in the Nature Chemical Biology journal, outlined the development of a new cancer treatment formed by isolating a rare class of molecules — ribosomally synthesized and post-translationally modified peptides — from Aspergillus flavus, a fungus typically associated with deadly aflatoxins. Chemical and Biological Engineering professor Sherry Gao and postdoctoral student Qiuyue Nie led the team in creating the compound to kill leukemia cells with potency comparable to FDA-approved therapies by modifying these molecules.
Nie explained the benefits of exploring RiPPs in a written statement to The Daily Pennsylvanian.
“Fungal natural products are an important source for drug screening, for example, penicillin is one of [the] most famous antibiotics used in clinics, Lovastatin is a medication used to lower high cholesterol levels,” Nie wrote. “Fungal RiPPs are a kind of unexplored type in fungal natural products, however, most of them exhibited bioactivity and close relationship to chemical ecology.”
The newly developed compound — part of a group the researchers called “asperigimycins” — showed significant promise in lab test results. “Lipid-modified asperigimycin matched the efficacy of frontline leukemia drugs while targeting leukemia cells more specifically,” Gao wrote to the DP. The “compounds’ novelty, selectivity and potency” reflects in “its ability to use a transporter protein that’s more active in leukemia cells.”
Gao and Nie’s team focused on Aspergillus flavus due to its rich genome and underexplored biosynthetic capabilities. Despite its reputation for producing dangerous toxins, the strain revealed entirely new RiPPs with previously uncharacterized structures — one of many surprises in the study, according to Nie.
Nie wrote that one of the “biggest challenges” in the project was the “highly complex” structure of the compounds.
“Many fungal molecules are made in tiny amounts and are structurally complex, making them hard to isolate at scale,” Gao agreed. “Another hurdle is getting them into cells without being degraded, which is why we invested in chemical modifications like lipid tagging.”
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According to Gao, the team hopes to identify the compound’s direct molecular targets and test its safety and efficacy on animal models. While clinical trials remain a few years away, she described her optimism for improvement. The researchers believe the work signals a broader shift in drug discovery — one that looks to fungi as a powerful source of therapeutic compounds.
“With better genomic tools and synthetic biology approaches, we’re only now starting to unlock their potential,” Gao wrote. “I think we’ll see a wave of fungal-derived compounds entering pipelines for cancer and many other diseases.”
