The B12 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 B12 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 B12‐cofactors for their challenging chemical transitions. The availability of Hby also provides a route to the synthesis of transition metal analogues of B12.

Vitamin B is made by only certain prokaryotes yet is required by a number of eukaryotes such as mammals, fish, birds, worms, and Protista, including algae. There is still much to learn about how this nutrient is trafficked across the domains of life. Herein, we describe ways to make a number of different corrin analogs with fluorescent groups attached to the main tetrapyrrole-derived ring. A further range of analogs were also constructed by attaching similar fluorescent groups to the ribose ring of cobalamin, thereby generating a range of complete and incomplete corrinoids to follow uptake in bacteria, worms, and plants. By using these fluorescent derivatives we were able to demonstrate that Mycobacterium tuberculosis is able to acquire both cobyric acid and cobalamin analogs, that Caenorhabditis elegans takes up only the complete corrinoid, and that seedlings of higher plants such as Lepidium sativum are also able to transport B.

Die B 12 -Cofaktoren erzeugen eine natürliche Neugier bezüglichd er ursprünglichen Selektion und Evolution ihres Corrin-Liganden. Bisher entzogs ich dieser wichtige na-türlicheM akrocyclus überraschenderweise einer detaillierten Untersuchung, sodass seine spezifischeR olle bei der Prädisposition des eingebauten Cobalt-Ions zur organometallischen Katalyse ungeklärt blieb.H ier berichten wir über die Hydrogenobyrsäure (Hby), den cobaltfreien Corrin-Liganden von Vitamin B 12 ,der über eine neuartig programmierte Biosynthese hergestellt wurde.D etaillierte Einblicke in die Rçntgen-Einkristall-und Lçsungs-Strukturen der Hby zeigten einen verzerrt helikalen Hohlraum, der das Bindungsmuster fürCobalt-Ionen in B 12 redefiniert. Der Corrin-Ligand koordiniert Cobalt-Ionen in unsymmetrischen entatischen Zuständen, was B 12 -Cofaktoren füra nspruchsvolle chemische Übergänge aktiviert. Die Verfügbarkeit von Hby erçffnet auch neue Syntheserouten für Übergangsmetallanaloga von Vitamin B 12 .