Salmonella enterica synthesizes 5,6-dimethylbenzimidazolyl-(DMB)-α-riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin

Mol Microbiol. 2017 Jan;103(2):269-281. doi: 10.1111/mmi.13555. Epub 2016 Nov 22.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / metabolism
  • Cobamides / biosynthesis*
  • Cobamides / metabolism
  • Firmicutes / metabolism
  • Multienzyme Complexes / metabolism
  • Nicotinamide Mononucleotide / analogs & derivatives
  • Nicotinamide Mononucleotide / metabolism
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Nucleotidyltransferases / metabolism
  • Phosphorylation
  • Ribonucleosides / biosynthesis*
  • Salmonella enterica / metabolism*


  • Bacterial Proteins
  • Cobamides
  • Multienzyme Complexes
  • Ribonucleosides
  • Nicotinamide Mononucleotide
  • alpha-ribazole
  • nicotinate mononucleotide
  • Nicotinamide Phosphoribosyltransferase
  • Nucleotidyltransferases
  • cobamamide