title: Salmonella enterica synthesizes 5,6-dimethylbenzimidazolyl-(DMB)-α-riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin.
abstract: 5,6-Dimethylbenzimidazolyl-(DMB)-α-ribotide [α-ribazole-5'-phosphate (α-RP)] is an intermediate in the biosynthesis of adenosylcobalamin (AdoCbl) in many prokaryotes. In such microbes, α-RP is synthesized by nicotinate mononucleotide (NaMN):DMB phosphoribosyltransferases (CobT in Salmonella enterica), in a reaction that is considered to be the canonical step for the activation of the base of the nucleotide present in adenosylcobamides. Some Firmicutes lack CobT-type enzymes but have a two-protein system comprised of a transporter (i.e., CblT) and a kinase (i.e., CblS) that can salvage exogenous α-ribazole (α-R) from the environment using CblT to take up α-R, followed by α-R phosphorylation by CblS. We report that Geobacillus kaustophilus CblT and CblS proteins restore α-RP synthesis in S. enterica lacking the CobT enzyme. We also show that a S. enterica cobT strain that synthesizes GkCblS ectopically makes only AdoCbl, even under growth conditions where the synthesis of pseudoCbl is favored. Our results indicate that S. enterica synthesizes α-R, a metabolite that had not been detected in this bacterium and that GkCblS has a strong preference for DMB-ribose over adenine-ribose as substrate. We propose that in some Firmicutes DMB is activated to α-RP via α-R using an as-yet-unknown route to convert DMB to α-R and CblS to convert α-R to α-RP.
authors.affiliation: Department of Microbiology, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Theodoric A
authors.initials: TA
authors.lastname: Mattes
authors.affiliation: Department of Microbiology, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Escalante-Semerena
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D003038:Cobamides / Q000096:biosynthesis* / Q000378:metabolism; D000068536:Bacillota / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D010766:Phosphorylation; D012263:Ribonucleosides / Q000096:biosynthesis*; D019779:Salmonella enterica / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003038:Cobamides; D009097:Multienzyme Complexes; D012263:Ribonucleosides; D009537:Nicotinamide Mononucleotide; C015491:alpha-ribazole; C002953:nicotinate mononucleotide; D054409:Nicotinamide Phosphoribosyltransferase; D009713:Nucleotidyltransferases; C000913:cobamamide