Engineered enzyme flirts with fluorine

There are many chemical methods for adding medicinally helpful fluorinated alkyl groups onto molecules, but doing so with high stereoselectivity can be a challenge. Enzymes, meanwhile, are superstars of stereoselectivity—but there’s only one enzyme that naturally works with fluorinated substrates. Fortunately, it’s possible to teach old enzymes new tricks. Researchers led by Huimin Zhao of the University of Illinois at Urbana-Champaign have engineered a light-activated enzyme to stereoselectively attach fluorinated alkyl groups to molecules that contain double bonds. They recently published a paper about the work in Science (2024, DOI: 10.1126/science.adk8464 ). Postdoctoral fellow Maolin Li, the paper’s first author, also presented the work at ACS Fall 2024. Zhao said that his group engineers enzymes with the goal of bringing together the versatility of radical photocatalysis and the selectivity of biocatalysis. The enxymes they work with are ene reductases which use a light-driven radical mechanism to facilitate stereoselective addition reactions