Engineering Enzymes for New‐to‐Nature Carbene Chemistry

Abstract

Transition metal catalysis has traditionally been at the forefront of carbene-mediated transformations. As a complement, a new paradigm that envisions the use of enzymes to harness carbene reactivity has arisen in the past decade. Natural proteins containing competent cofactors like heme can promote carbene transfer chemistry. Directed evolution of such proteins, along with the exploration of artificial metalloproteins, has enabled the development of efficient enzyme catalysts for cyclopropanation and X–H insertion reactions with exquisite selectivity. Enzymatic carbene chemistry is emblematic of a new age of biocatalysis, where new-to-nature reactions can revolutionize the capabilities of synthetic chemistry.