Researchers crack the synthetic code of rare molecules

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A research team from Lund University in Sweden has succeeded in producing two molecules in a disused mine in South Korea that are otherwise only formed by microorganisms from heavily polluted wastewater. The method, which took four years to develop, could pave the way for novel drugs. The study is published in Journal of the American Chemical Society.

Glionitrin A and B are two molecules with properties that make them useful tools in drug development. However, researchers who want to harness these molecules have faced an uphill battle for nearly a decade.

Glionitrin A and B are natural products and are produced by a fungus found in extremely contaminated acidic sewage from a decommissioned South Korean mine. Since the fungus only makes the molecules by releasing certain bacteria from the same wastewater, it has proven difficult to make them through fermentation.

“We have been working on this problem for four years. Every time we thought we had a solution, the molecules showed unexpected properties that sent us back to the drawing board, ”says Daniel Strand, chemical researcher at Lund University.

Despite the complexity of the problem, the solution turned out to be simpler and more effective than the researchers thought. By developing a new so-called asymmetric organocatalytic reaction, Daniel Strand and his colleagues succeeded in forging the most inaccessible parts of the molecules.

“Even when we thought the problem was finally solved, the molecule had one final surprise. It turned out that the real structure was the mirror image of what we originally thought was glionitrin A. So all along, we and others had been chasing a molecule that was never there,“Says beach.

Complex natural substances with unique properties such as glionitrin A and B are important tools in drug development.

Glionitrin A has shown antibiotic properties against resistant bacteria, while glionitrin B makes cancer cells less prone to migration. The ability to make the molecules synthetically helps researchers not only understand how they work, but also improve their properties.

“There is a great need for new types of antibiotics, especially those that can help fight resistant bacteria. We expect that our results will stimulate further developments in basic synthetic chemistry, but will also be used in drug development, ”concluded Strand.

– This press release was originally published on the Lund University website


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