Non-natural carbenoid and nitrenoid insertion reactions catalyzed by heme proteins

Despite increasing interest in using enzymes as tools for synthesis, many reactions discovered through the creativity of synthetic chemists remain beyond the scope of biocatalysis. This vacancy in the field has compelled researchers to develop strategies to adapt protein scaffolds for new reactivity. Heme proteins have recently been shown to activate synthetic precursors to generate reactive metallocarbenoid and metallonitrenoid species that enable the biosynthetic construction of novel C-C, C-N, and other bonds using mechanisms not previously explored by Nature. By interrogating heme proteins with synthetic, non-natural reagents, scientists are merging the reaction space traditionally dominated by organocatalysis and transition metal catalysis with the mild reaction conditions, selectivity, and adaptability imparted by native protein scaffolds.