Discovery of bumblebee medicine’s simple structure makes synthetic production viable

Researchers at the University of Chemistry and Technology, Prague have successfully developed a method to chemically synthesize callunene, a natural compound that protects bumblebees from a deadly gut parasite. In a recent discovery, the team also determined that the naturally occurring compound is a 50/50 mixture of its mirror-image forms, meaning the synthetic version can be used directly to safeguard vital pollinator colonies.

The study, published in the Journal of Natural Products, addresses the threat posed by the parasite Crithidia bombi. This protozoan infects bumblebees, impairing their ability to find nectar-rich flowers, which ultimately leads to starvation, reduced colony fitness, and death. The problem is especially acute in commercial indoor farming operations that rely on healthy pollinator colonies. Not only because of the farming effectiveness, but also because parasites might be spread from indoor pollinators to wild colonies.

Nature provides a defense in the form of callunene, a compound found in the nectar of heather (Calluna vulgaris). Bumblebees that forage on heather are prophylactically protected from Crithidia infection. However, the loss of heathland habitats and the difficulty of isolating the compound from natural sources have made this solution impractical on a large scale.

The UCT Prague team, led by Dr. Pavla Perlíková, overcame this challenge by developing a five-step synthesis to produce callunene in the lab. More importantly, they solved a long-standing chemical mystery about the compound’s three-dimensional structure.

“We saw a clear threat to our vital pollinators from parasites like Crithidia bombi,” said Dr. Perlíková, a lead researcher at UCT Prague. “Nature offered a solution in callunene, but it wasn’t a practical one due to its scarcity. Our goal was to make this natural protection accessible.”

Using advanced analytical techniques, including nuclear magnetic resonance (NMR) spectroscopy, the researchers analyzed both their synthetic callunene and the compound isolated from heather honey. They found that natural callunene exists as a racemic mixture—an equal blend of its “left-handed” and “right-handed” molecular forms (enantiomers).

“The most exciting part of this work was solving the stereochemical puzzle of callunene,” Dr. Perlíková explained. “Discovering that natural callunene is a racemic mixture was a game-changer. It means our synthetic version is essentially bio-identical for this purpose, and we can now produce it in the quantities needed for prophylactic studies to demonstrate its potential for use in protecting pollinator colonies. This removes a major economic and technical barrier to its use.”

This finding is significant because it means the synthetic callunene does not require an additional, often complex and expensive, step to separate the two enantiomers. The synthetic mixture can be used directly as an additive to the food of pollinators, offering a way to protect them from parasitic infections. The research opens the door for further studies and the development of new prophylactic treatments to ensure the health of these essential insects.