Abstract
Nitrogenase employs a sophisticated electron transfer system and a Mo-Fe-S-C cofactor, designated the M-cluster [(cit)MoFe(7) S(9) C]), to reduce atmospheric N(2) to bioaccessible NH(3) . 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 [Fe(6) S(9) (SEt)(2) ](4-) . Here, we demonstrate the utility of an asymmetric Mo-Fe-S cluster [Cp*MoFe(5) S(9) (SH)](3-) as an alternative artificial cofactor upon incorporation into the cofactor-free nitrogenase scaffold. The resultant semi-artificial enzyme catalytically reduces C(2) H(2) to C(2) H(4) , and CN(-) into short-chain hydrocarbons, yet it is clearly distinct in activity from its [Fe(6) S(9) (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.