Incorporation of an Asymmetric Mo−Fe−S Cluster as an Artificial Cofactor into Nitrogenase

Nitrogenase employs a sophisticated electron transfer system and a Mo−Fe−S−C cofactor, designated the M‐cluster [(cit)MoFe7S9C]), to reduce atmospheric N2 to bioaccessible NH3. Previously, we have shown that the cofactor‐free form of nitrogenase can be repurposed as a protein scaffold for the incorporation of a synthetic Fe−S cluster [Fe6S9(SEt)2]4−. Here, we demonstrate the utility of an asymmetric Mo−Fe−S cluster [Cp*MoFe5S9(SH)]3− as an alternative artificial cofactor upon incorporation into the cofactor‐free nitrogenase scaffold. The resultant semi‐artificial enzyme catalytically reduces C2H2 to C2H4, and CN− into short‐chain hydrocarbons, yet it is clearly distinct in activity from its [Fe6S9(SEt)2]4−‐reconstituted counterpart, pointing to the possibility to employ molecular design and cluster synthesis strategies to further develop semi‐artificial or artificial systems with desired catalytic activities. Incorporation of a synthetic asymmetric Mo−Fe−S cluster, [Cp*MoFe5S9(SH)]3−, into the active site of the cofactor‐free nitrogenase scaffold results a semi‐artificial enzyme that catalytically reduces C2H2 to C2H4, and CN− into short‐chain hydrocarbons.