A metallophotoredox strategy for biocatalytic radical C-N₃ and C-SCN bond formatio

Metallophotoredox catalysis, an approach that combines photoredox and transition metal catalysis, has emerged as a powerful strategy in modern synthetic chemistry. This dual-catalyst system takes advantage of the broad mechanisms of photocatalysts for substrate activation and the capabilities of transition metal complexes to control reactive radical species. Its modular nature allows each catalytic component to be independently tuned for desired reactivity and selectivity. Despite its significance on synthetic methodologies, biocatalytic analogs of metallophotoredox catalysis remain largely unexplored. To bridge this gap, our group has recently discovered that several nonheme iron enzymes can be combined with synthetic photocatalysts such as eosin Y and fluorescein to enable radical generation from redox-active NHPI esters. The resulting substrate radicals can then be selectively intercepted by the enzymes to promote enantioselective transformations. Particularly, we have successfully repurposed a nonheme iron enzyme, (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis (SavHPPD), to catalyze enantioselective photoredox decarboxylative C-N₃ and C-SCN bond formation. This chapter provides a detailed experimental protocol for this latest development in biocatalytic metallophotoredox catalysis. Moreover, the outlined procedures could serve as a general framework for engineering metalloenzymes toward new photocatalytic functions.