Iron-sulfur clusters have been reported to catalyze various redox transformations, including the multielectron reduction of CO2 to hydrocarbons. Herein, we report the design and assembly of an artificial [Fe4S4]-containing Fischer-Tropschase relying on the biotin-streptavidin technology. For this purpose, we synthesized a bis-biotinylated [Fe4S4] cofactor with marked aqueous stability and incorporated it in streptavidin. The effect of the second coordination sphere provided by the protein environment was scrutinized by cyclic voltammetry, highlighting the accessibility of the doubly reduced [Fe4S4] cluster. The Fischer-Tropschase activity was improved by chemo-genetic means for the reduction of CO2 to hydrocarbons with up to 14 turnovers.