One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica

Peter J. Anderson, Jozsef Lango, Colleen Carkeet, Audrey Britten, Bernhard Kräutler, Bruce D. Hammock, John R. Roth

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Corrinoid (vitamin B12-like) cofactors contain various α-axial ligands, including 5,6-dimethylbenzimidazole (DMB) or adenine. The bacterium Salmonella enterica produces the corrin ring only under anaerobic conditions, but it can form "complete" corrinoids aerobically by importing an "incomplete" corrinoid, such as cobinamide (Cbi), and adding appropriate α- and β-axial ligands. Under aerobic conditions, S. enterica performs the corrinoid-dependent degradation of ethanolamine if given vitamin B12, but it can make B12 from exogenous Cbi only if DMB is also provided. Mutants isolated for their ability to degrade ethanolamine without added DMB converted Cbi to pseudo-B12 cofactors (having adenine as an α-axial ligand). The mutations cause an increase in the level of free adenine and install adenine (instead of DMB) as an α-ligand. When DMB is provided to these mutants, synthesis of pseudo-B12 cofactors ceases and B12 cofactors are produced, suggesting that DMB regulates production or incorporation of free adenine as an α-ligand. Wild-type cells make pseudo-B12 cofactors during aerobic growth on propanediol plus Cbi and can use pseudo-vitamin B12 for all of their corrinoid-dependent enzymes. Synthesis of coenzyme pseudo-B12 cofactors requires the same enzymes (CobT, CobU, CobS, and CobC) that install DMB in the formation of coenzyme B12. Models are described for the mechanism and control of α-axial ligand installation.

Original languageEnglish (US)
Pages (from-to)1160-1171
Number of pages12
JournalJournal of Bacteriology
Volume190
Issue number4
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Immunology

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    Anderson, P. J., Lango, J., Carkeet, C., Britten, A., Kräutler, B., Hammock, B. D., & Roth, J. R. (2008). One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica. Journal of Bacteriology, 190(4), 1160-1171. https://doi.org/10.1128/JB.01386-07