Investigating the role of the strong field ligands in [FeFe] hydrogenase: spectroscopic and functional characterization of a semi-synthetic mono-cyanide active site

Marco Lorenzi (1) , Joe Gellett (2) , Afridi Zamader (3, 1) , Moritz Senger (1) , Zehui Duan (2) , Patricia Rodriguez-Macia , Gustav Berggren

1 Uppsala University
2 University of Oxford
3 SolHyCat - Solar fuels, hydrogen and catalysis

Artificial maturation of hydrogenases provides a path towards generating new semi-synthetic enzymes with novel catalytic properties. Here enzymes featuring a synthetic asymmetric mono-cyanide cofactor have been prepared using two different hydrogenase scaffolds. Their structure and reactivity was investigated in order to elucidate the design rationale behind the native di-cyanide cofactor, and by extension the second coordination sphere of the active-site pocket. Surprisingly, the choice of host enzyme was found to have a dramatic impact on reactivity. Moreover, the study shows that synthetic manipulations of the active-site can significantly increase inhibitor tolerance, as compared to native [FeFe] hydrogenase, while retaining the enzyme's native capacity for reversible catalysis.

Domains: Coordination chemistry; Theoretical and/or physical chemistry

Marco Lorenzi, Joe Gellett, Afridi Zamader, Moritz Senger, Zehui Duan, et al.. Investigating the role of the strong field ligands in [FeFe] hydrogenase: spectroscopic and functional characterization of a semi-synthetic mono-cyanide active site. Chemical Science, 2022, 13 (37), pp.11058-11064. ⟨10.1039/d2sc02271k⟩. ⟨hal-04041579⟩