Good news! Cancer is history (soon)!
"... After isolating a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to deaths in the excavations of ancient tombs, the researchers modified the chemicals and tested them against leukemia cells. The result? A promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines. ...
The therapy in question is a class of ribosomally synthesized and post-translationally modified peptides, or RiPPs, ... The name refers to how the compound is produced — by the ribosome ... and the fact that it is modified later, in this case, to enhance its cancer-killing properties.
“Purifying these chemicals is difficult,” ... While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. ...
After purifying four different RiPPs, the researchers found the molecules shared a unique structure of interlocking rings. The researchers named these molecules, which have never been previously described, after the fungus in which they were found: asperigimycins.
Even with no modification, when mixed with human cancer cells, asperigimycins demonstrated medical potential: two of the four variants had potent effects against leukemia cells. ..."
From the abstract:
"Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored.
Here we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases.
Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus.
A derivative with a C-11 linear fatty acid, 2-L6, achieves nanomolar anticancer potency comparable to that of clinically approved antileukemia drugs.
High-throughput CRISPR screening identifies the SLC46A3 transporter as a critical factor mediating 2-L6 cellular uptake into human cells.
Our findings highlight the promise of engineering asperigimycins as therapeutic leads for cancer treatment."
Penn Engineers Turn Toxic Fungus into Anti-Cancer Compound (original news release)
A class of benzofuranoindoline-bearing heptacyclic fungal RiPPs with anticancer activities (no public access)
Adding lipids to the newly discovered chemicals helped the asperigimycins enter cells.
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