The three were published in the May 2022 issue of Science for their work on engineering nonheme iron enzymes for new-to-nature chemistry

Despite the rapid development of enzymes for non-natural transformations in the past decade, only a limited set of synthetic reactions has been imported into the biocatalysis toolbox. To this end, the Huang group reported the reprogramming of nonheme iron enzymes to catalyze a novel C(sp³)‒H azidation reaction via iron-catalyzed radical relay, a reaction mechanism that is not utilized by naturally occurring enzymes. This new-to-nature biotransformation features the use of amidyl radicals as hydrogen atom abstractors and Fe(III)‒N₃ intermediates as radical trapping agents. A high-throughput screening platform based on click chemistry was established which enables the rapid evolution of the catalytic performance of enzymes identified via directed evolution. The final optimized variants function in whole Escherichia coli cells and deliver a range of azidation products with up to 10600 total turnovers and 93% enantiomeric excess. Given the high prevalence of radical relay reactions in organic synthesis and the large diversity of NHFe enzymes, this discovery will stimulate future development of metalloenzyme catalysts for synthetically useful transformations unexplored by natural evolution.