Scientists have finally solved a 50-year-old fungal puzzle.
According to a new study published in the Journal of the American Chemical Society, chemists at MIT have finally cracked the code on synthesising Verticillin A - a compound found in fungi that scientists have been eyeing since 1970.
And early tests suggest it has potential for treating certain types of brain cancer, especially in kids.
Why Did This Take Half a Century?
Verticillin A and related fungal compounds have drawn interest for their potential anticancer and antimicrobial activity, but their complexity has made them difficult to synthesise.
Back in 2009, the same MIT lab managed to synthesise a nearly identical compound called (+)-11,11'-dideoxyverticillin A. The difference between that molecule and verticillin A is just two oxygen atoms.
But as MIT chemistry professor Mohammad Movassaghi explains, those two tiny oxygens made things exponentially harder. They made the molecule "so much more fragile, so much more sensitive" that even with years of advances in chemistry techniques, it remained maddeningly out of reach.
Those oxygen atoms basically meant the researchers had to rethink their entire approach, changing the order of operations in a synthesis that already required 16 painstaking steps.
The Breakthrough
What finally worked was getting the timing exactly right. The team had to add certain chemical groups earlier in the process than they'd done with the similar compound, carefully "masking" and protecting sensitive parts of the molecule so they wouldn't fall apart during later steps. It's chemistry as precision engineering.
Now, after more than 50 years, they can now not only make verticillin A, but also create custom variants of it to test for different medical applications.
The Cancer Connection
This is where things get really interesting. Fungi produce verticillin A as protection against pathogens, but researchers have long suspected it might have anticancer properties. Now we're getting proof.
When the team at Dana-Farber Cancer Institute tested derivatives of verticillin A against diffuse midline glioma, a rare and particularly nasty paediatric brain tumour, they found something promising. The compounds were especially effective against cancer cells with high levels of a protein called EZHIP, which has been identified as a potential drug target for this type of cancer.
The best-performing compounds were modified versions of both verticillin A and its predecessor, tweaked to make them more stable by adding sulfur and oxygen groups. Apparently the natural version isn't the most potent on its own, but now that scientists can synthesise it, they can fine-tune it to be more effective.
What's Next?
The researchers are now working on two fronts: confirming exactly how these compounds kill cancer cells, and testing them in animal models of paediatric brain cancers. If those tests go well, we could be looking at new treatment options for cancers that currently have very few.
The research was funded by the National Institute of General Medical Sciences, the Ependymoma Research Foundation, and the Curing Kids Cancer Foundation, so there's clearly institutional interest in pushing this forward.
It's still early days, obviously. We're talking about lab and cell studies here, not human trials. But after 50 years, it feels like scientists are finally getting somewhere with this mysterious fungal compound.
What do you think about fungi as medicine factories? Drop your thoughts in the comments below.
