Researchers at the University of Basel have engineered a natural enzyme to catalyze a highly selective and challenging chemical reaction, paving the way for more sustainable methods to synthesize complex molecules such as pharmaceuticals and fine chemicals. Their approach combines enzymatic catalysis with a cutting edge method known as metal hydride hydrogen atom transfer MHAT, offering a greener and more efficient route to chemical synthesis.

MHAT involves transferring a hydrogen atom from a metal hydride to a double bond in an organic molecule, generating a reactive intermediate that drives the formation of complex, three dimensional structures. However, controlling the exact spatial arrangement particularly producing only one of two mirror image  chiral forms remains a major challenge. This is critical in drug manufacturing, where the two forms can differ drastically in biological activity.

The Basel team overcame this by repurposing a naturally occurring haemoprotein to carry out MHAT reactions within its catalytic site. This engineered enzyme not only performs the reaction but does so with remarkable precision, favoring the desired chiral form of the product in up to a 98:2 ratio. Such selectivity is extremely difficult to achieve with conventional catalysts.

Published in Nature, the study is part of the National Center of Competence in Research  Molecular Systems Engineering, led by Prof. Dr. Thomas R. Ward. According to first author Dr. Xiang Zhang, this is the first time an enzyme has been shown to perform MHAT chemistry marking a significant step forward in biocatalysis and sustainable chemical manufacturing.

Source: https://www.unibas.ch/en/News-Events/News/Uni-Research/Engineered-enzyme-to-precisely-build-complex-molecules.html#:~:text=Researchers%20at%20the%20University%20of,environmentally%20friendly%20and%20efficient%20way