title: Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non-Natural Rhodium Homologue of Coenzyme B12.
abstract: B12 is unique among the vitamins as it is biosynthesized only by certain prokaryotes. The complexity of its synthesis relates to its distinctive cobalt corrin structure, which is essential for B12 biochemistry and renders coenzyme B12 (AdoCbl) so intriguingly suitable for enzymatic radical reactions. However, why is cobalt so fit for its role in B12 -dependent enzymes? To address this question, we considered the substitution of cobalt in AdoCbl with rhodium to generate the rhodium analogue 5'-deoxy-5'-adenosylrhodibalamin (AdoRbl). AdoRbl was prepared by de novo total synthesis involving both biological and chemical steps. AdoRbl was found to be inactive in vivo in microbial bioassays for methionine synthase and acted as an in vitro inhibitor of an AdoCbl-dependent diol dehydratase. Solution NMR studies of AdoRbl revealed a structure similar to that of AdoCbl. However, the crystal structure of AdoRbl revealed a conspicuously better fit of the corrin ligand for Rh(III) than for Co(III) , challenging the current views concerning the evolution of corrins.
authors.affiliation: Institut für Organische Chemie und Centrum für Molekulare Biowissenschaften (CMBI), Universität Innsbruck, 6020, Innsbruck, Austria.|Plant and Microbial Biology Department, University of California, Berkeley, CA, USA.
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Widner
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Lawrence
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Deery
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
authors.forename: Dana
authors.initials: D
authors.lastname: Heldt
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Frank
authors.affiliation: Institut für Molekulare Biowissenschaften, Universität Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Gruber
authors.affiliation: Institut für Allgemeine, Anorganische und Theoretische Chemie, Universität Innsbruck, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wurst
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK. M.J.Warren@kent.ac.uk.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Warren
authors.affiliation: Institut für Organische Chemie und Centrum für Molekulare Biowissenschaften (CMBI), Universität Innsbruck, 6020, Innsbruck, Austria. bernhard.kraeutler@uibk.ac.at.
authors.forename: Bernhard
authors.identifier: 0000-0002-2222-0587
authors.initials: B
authors.lastname: Kräutler
mesh_terms: D016971:Citrobacter freundii / Q000201:enzymology; D003038:Cobamides / Q000737:chemistry / Q000494:pharmacology*; D045728:Corrinoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D003038:Cobamides; D045728:Corrinoids; C000628151:adenosylrhodibalamin; D013401:Sugar Alcohol Dehydrogenases; C020672:glycerol dehydrogenase; C000913:cobamamide
keywords: Vitamin B12; biosynthesis; cobalt; total synthesis; transition metal