The Hydrogenobyric Acid Structure Reveals the Corrin Ligand as an Entatic State Module Empowering B(12) Cofactors for Catalysis

The B(12) cofactors instill a natural curiosity regarding the primordial selection and evolution of their corrin ligand. Surprisingly, this important natural macrocycle has evaded molecular scrutiny, and its specific role in predisposing the incarcerated cobalt ion for organometallic catalysis has remained obscure. Herein, we report the biosynthesis of the cobalt‐free B(12) corrin moiety, hydrogenobyric acid (Hby), a compound crafted through pathway redesign. Detailed insights from single‐crystal X‐ray and solution structures of Hby have revealed a distorted helical cavity, redefining the pattern for binding cobalt ions. Consequently, the corrin ligand coordinates cobalt ions in desymmetrized “entatic” states, thereby promoting the activation of B(12)‐cofactors for their challenging chemical transitions. The availability of Hby also provides a route to the synthesis of transition metal analogues of B(12).