%0 Journal Article %T C-H functionalization reactions catalyzed by artificial metalloenzymes. %A Yu K %A Ward TR %J J Inorg Biochem %V 258 %N 0 %D 2024 Sep 31 %M 38852295 %F 4.336 %R 10.1016/j.jinorgbio.2024.112621 %X CH functionalization, a promising frontier in modern organic chemistry, facilitates the direct conversion of inert CH bonds into many valuable functional groups. Despite its merits, traditional homogeneous catalysis, often faces challenges in efficiency, selectivity, and sustainability towards this transformation. In this context, artificial metalloenzymes (ArMs), resulting from the incorporation of a catalytically-competent metal cofactor within an evolvable protein scaffold, bridges the gap between the efficiency of enzymatic transformations and the versatility of transition metal catalysis. Accordingly, ArMs have emerged as attractive tools for various challenging catalytic transformations. Additionally, the coming of age of directed evolution has unlocked unprecedented avenues for optimizing enzymatic catalysis. Taking advantage of their genetically-encoded protein scaffold, ArMs have been evolved to catalyze various CH functionalization reactions. This review delves into the recent developments of ArM-catalyzed CH functionalization reactions, highlighting the benefits of engineering the second coordination sphere around a metal cofactor within a host protein.