B12-Cofactor Inactivation by Cobalt to Rhodium Mutation in Methylrhodibalamin: An Antivitamin B12 and Antibiotic

Widner FJ, Wurst K, Ruetz M, Kieninger C, Kreutz C, Paxhia M, Deery E, Warren MJ, Krautler B. (2025)

ChemistryEurope

Cobalt-corrins, such as coenzyme B₁₂ (AdoCbl) and methylcobalamin (MeCbl), are indispensable enzyme-cofactors found across all kingdoms of life. Their Rh-homologues are promising coordination-chemical and structural B₁₂-mimics. Herein, the preparation of methylrhodibalamin (MeRhbl) in over 90% yield is reported, achieved through template-assisted assembly from Rh_ß-methylrhodibyrate and the B₁₂-nucleotide. NMR and X-ray crystallography studies confirm that MeRhbl is iso-structural with the B₁₂-cofactor MeCbl. The human B₁₂-tailoring enzyme CblC binds and activates MeRhbl, but Rh-demethylation of MeRhbl is inhibited by its stable Rh-C bond, whose strength is also determined. Thus, MeRhbl meets the key criteria for a genuine antivitamin B₁₂, making it a useful tool for biomedical applications. The B₁₂-antimetabolite MeRhbl also acts as an effective growth inhibitor of the acne-causing bacterium Cutibacterium acnes.

ChemistryEurope

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