Blitz Bureau
NEW DELHI: A team of US researchers has turned a deadly fungus into a potent cancer-fighting compound, according to a new study. 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 was a promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines, according to the study by University of Pennsylvania’s School of Engineering and Applied Science.
“Fungi gave us penicillin. These results show that many more medicines derived from natural products remain to be found,” said Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and senior author of a new paper in Nature Chemical Biology journal. The therapy in question is a class of ribosomally synthesized and post-translationally modified peptides, or RiPPs, pronounced like the “rip” in a piece of fabric.
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, in this case, to enhance its cancer-killing properties. “Purifying these chemicals is difficult,” says Qiuyue Nie, a postdoctoral fellow in CBE and the paper’s first author.
While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. In part, this is because past researchers misidentified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi created the molecules.
“The synthesis of these compounds is complicated,” adds Nie. “But that’s also what gives them this remarkable bioactivity.” To find more fungal RiPPs, the researchers 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.
