Unusual aerobic stabilization of Cob(I)alamin by a B12-trafficking protein allows chemoenzymatic synthesis of organocobalamins.

Abstract

CblC, a B12 trafficking protein, exhibits glutathione transferase and reductive decyanase activities for processing alkylcobalamins and cyanocobalamin, respectively, to a common intermediate that is subsequently converted to the biologically active forms of the cofactor. We recently discovered that the Caenorhabditis elegans CblC catalyzes thiol-dependent decyanation of CNCbl and reduction of OH2Cbl and stabilizes the paramagnetic cob(II)alamin product under aerobic conditions. In this study, we report the striking ability of the worm CblC to stabilize the highly reactive cob(I)alamin product of the glutathione transferase reaction. The unprecedented stabilization of the supernucleophilic cob(I)alamin species under aerobic conditions by the intrinsic thiol oxidase activity of CblC, was exploited for the chemoenzymatic synthesis of organocobalamin derivatives under mild conditions.