Can photolysis of the CoC bond in coenzyme B 12 -dependent enzymes be used to mimic the native reaction?

Coenzyme B ₁₂ (Adenosylcobalamin = AdoCbl)-dependent enzymes catalyze complex molecular transformations where cleavage of the CoC bond initiates the catalytic cycle. Alternatively, the CoC bond can be cleaved with light. In both cases, rupture of the CoC bond results in the formation of Co(II)/Ado radical pair (RP). Within the field of B ₁₂ chemistry, there has been a suspicion that photolytic cleavage can be used as a probe or a direct comparison of the native reaction. Herein, we seek to resolve what the connection between light induced RP formation and the native catalytic cycle is. We used a combined QM/MM approach to construct PESs for AdoCbl-dependent ethanolamine ammonia-lyase (EAL) as a function of axial bonds to describe the reaction mechanism. We have found that there is no direct comparison that can be made between photolysis and enzymatic cleavage as the mechanism associated with these involves different electronic states. With that being said, we have explored an alternate hypothesis for the connection which involves the one-electron reduced form of the AdoCbl cofactor. This hypothesis is in line with the concept based on proton-coupled electron transfer (PCET), which involves the formation of AdoCbl cofactor-tyrosine diradical complex. The topology of the PES for the one-electron reduced (D ₁ ) cofactor is very similar to the PES associated with photo-induced cleavage (S ₁ ). Both surfaces contain two energy minima that are, similarly, the result of two distinct electronic states. Thus, it appears that the reaction mechanism associated with the D ₁ surface and the S ₁ surface are very similar, providing a plausible connection between photolysis and native catalysis.
(Copyright © 2018. Published by Elsevier B.V.)