A major consideration in designing an organic synthesis is the selective activation of a center that enables a new bond to be made or an existing bond to be broken. For instance, protons bound to a carbon that is adjacent to a carbonyl are more readily abstracted than alkyl protons. The synthetic chemist is able to bring to bear a sophisticated armamentarium of reagents and catalysts in addition to the capability of manipulating the solvent and environmental conditions. In contrast, microbes rely on enzymes that, in most cases, operate at ambient temperatures and pressures in aqueous solution at physiological pH.
In one such case, the energetically difficult reduction (dearomatization) of benzoyl-CoA is achieved by using the stoichiometric hydrolysis of ATP to drive the addition of two electrons to the aromatic ring, in a fashion that is somewhat similar to the even more difficult reduction of dinitrogen that is catalyzed by nitrogenase. Unciuleac and Boll present biochemical evidence for the formation of a phosphorylated intermediate of benzoyl-CoA reductase. They suggest that the energy of the phosphoanhydride bond is used to activate an electron in the guise of converting one of the intrinsic [4Fe-4S] clusters into a high-spin state that then initiates the reduction of the substrate. -- GJC
Proc. Natl. Acad. Sci. U.S.A., 10.1073/pnas.241375598.
