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Abstract Native metalloenzymes are unparalleled in their ability to perform efficient small molecule activation reactions, converting simple substrates into complex products. Most of these natural systems possess multiple metallocofactors to facilitate electron transfer or cascade catalysis. While the field of artificial metalloenzymes is growing at a rapid rate, examples of artificial enzymes that leverage two distinct cofactors remain scarce. In this work, we describe a new class of artificial enzymes containing two different metallocofactors, incorporated through bioorthogonal strategies. Nickel-substituted rubredoxin (Ni^Rd), which is a structural and functional mimic of [NiFe] hydrogenases, is used as a scaffold. Incorporation of a synthetic bimetallic inorganic complex based on a macrocyclic biquinazoline ligand (M^MBQ) was accomplished using a novel chelating thioether linker. Neither the structure of the Ni^Rdactive site nor the M^MBQwere altered upon attachment, and each site retained independent redox activity. Electrocatalysis was observed from each site, with the switchability of the system demonstrated through the use of catalytically inert metal centers. This M^MBQ–Ni^Rdplatform offers a new avenue to create multicofactor artificial metalloenzymes in a robust system that can be easily tuned both through modifications to the protein scaffold and the synthetic moiety, with applications for redox catalysis and tandem reactivity. Graphical abstract