Over the past three decades, the advent of directed evolution has enabled enhancements to catalytic activity and stereoselectivity through customized enzymes; demonstrating the potential of biocatalysis to revolutionize the practice of asymmetric synthesis. Until recently, however, the catalytic repertoire of enzymes has been mostly limited to reactions found in nature, posing constraints on the types of products available from enzyme catalysis. Furthermore, to date, a variety of catalysis modes discovered and optimized by synthetic chemists has remained out of reach of natural enzymes. It follows that bringing new catalytic functions to naturally-occurring enzymes can dramatically expand the repertoire of enzymology and generate novel biocatalysts applicable to fields such as pharmaceuticals and agrochemistry.
Researchers at the University of California, Santa Barbara have repurposed naturally occurring metalloenzymes to catalyze unnatural radical reactions in a stereocontrolled fashion. Steering the absolute and relative stereochemistry of these free radical processes is notoriously difficult in asymmetric catalysis, however, this technology imposes excellent stereocontrol over the radical addition step and the halogen rebound step, allowing enantio- and diastereodivergent radical catalysis to be easily carried out. These metalloenzymes are fully genetically encoded, highly active at room temperature (up to 20,000 total turnover number), and readily function in bacterial cells and cell-free lysates. This evolvable metalloenzyme platform represents a promising solution to tame fleeting radical intermediates for asymmetric catalysis.