The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6-dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole, an intermediate in the synthesis of the nucleotide loop of cobalamin

Trzebiatowski, Jodi R.; O’Toole, George A.; Escalante‐Semerena, Jorge C.

doi:10.1128/jb.176.12.3568-3575.1994

Cited by 63 publications

(72 citation statements)

References 21 publications

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“…Escalante-Semerena and coworkers have posited that the enzymes for this alternate pathway for phosphoribosyl transfer are encoded by the Salmonella cobB and/or cobC gene ( Fig. 1) (48,49,64); this explanation is supported by the findings of Chen et al (12). Since E. coli cobT mutations also fail to yield CobIII Ϫ phenotypes, E. coli may harbor homologs to the Salmonella cobB and cobC genes.…”

Section: Discussionsupporting

confidence: 66%

“…The question why E. coli cobT mutations yield CobII phenotypes remains to be answered. One possibility is that internal DMB synthesis provides insufficient DMB for the CobB and CobC proteins, which are presumably not acting on their preferred substrates (49,64). More likely, the E. coli CobT protein participates directly in the synthesis of DMB, as the data of Chen et al (11) suggest.…”

Section: Discussionmentioning

confidence: 64%

“…This phenotype is somewhat surprising. The E. coli CobT protein is homologous to the S. typhimurium CobT and P. denitrificans CobU proteins, which both perform the nicotinate mononucleotide::DMB phosphoribosyltransferase reaction (10,64). Loss of this function should result in a CobIII phenotype, since DMB and cobinamide would not correct the defect.…”

Section: Discussionmentioning

confidence: 99%

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The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli

Lawrence

Roth

1995

J Bacteriol

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The enteric bacterium Escherichia coli synthesizes cobalamin (coenzyme B 12 ) only when provided with the complex intermediate cobinamide. Three cobalamin biosynthetic genes have been cloned from Escherichia coli K-12, and their nucleotide sequences have been determined. The three genes form an operon (cob) under the control of several promoters and are induced by cobinamide, a precursor of cobalamin. The cob operon of E. coli comprises the cobU gene, encoding the bifunctional cobinamide kinase-guanylyltransferase; the cobS gene, encoding cobalamin synthetase; and the cobT gene, encoding dimethylbenzimidazole phosphoribosyltransferase. The physiological roles of these sequences were verified by the isolation of Tn10 insertion mutations in the cobS and cobT genes. All genes were named after their Salmonella typhimurium homologs and are located at the corresponding positions on the E. coli genetic map. Although the nucleotide sequences of the Salmonella cob genes and the E. coli cob genes are homologous, they are too divergent to have been derived from an operon present in their most recent common ancestor. On the basis of comparisons of G؉C content, codon usage bias, dinucleotide frequencies, and patterns of synonymous and nonsynonymous substitutions, we conclude that the cob operon was introduced into the Salmonella genome from an exogenous source. The cob operon of E. coli may be related to cobalamin synthetic genes now found among non-Salmonella enteric bacteria.Although commonly touted as one of the largest and oldest of the cofactors participating in modern biochemistry (20,23,59,60), the physiological importance of cobalamin (coenzyme B 12 ), especially among enteric bacteria, has remained enigmatic (58, 63). Cobalamin is derived from uroporphyrinogen III, a precursor in the synthesis of heme, siroheme, and chlorophylls as well as cobamides (Fig. 1). The conversion of uroporphyrinogen III to the complex intermediate cobinamide is referred to as part I of the biosynthetic pathway (hereafter designated CobI). Part II of the pathway (CobII) entails the biosynthesis of dimethylbenzimidazole (DMB) from probable flavin precursors (11,27,39). The covalent linkage of cobinamide, DMB, and a phosphoribosyl group donated by nicotinate mononucleotide is achieved by part III of the pathway (CobIII). Although most enteric bacteria can synthesize cobalamin de novo under either aerobic or anaerobic conditions (38), Escherichia coli synthesizes cobalamin only when provided with the complex intermediate cobinamide (38, 66); therefore, E. coli performs only parts II and III of the cobalamin biosynthetic pathway.The cobalamin biosynthetic genes in the closely related enteric bacterium Salmonella typhimurium have been characterized, and most constitute a large, 20-gene operon located at min 41 on the genetic map (28, 29, 52). It has been proposed that these genes are not ancestral to the Salmonella chromosome but have been introduced by horizontal transfer at or following the divergence of the salmonellae from Escherichia speci...

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli

Lawrence

Roth

1995

J Bacteriol

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“…Although this enzyme is a phosphoribosyltransferase, it does not utilize PRPP as a substrate. Rather, the 5-phosphoribosyl moiety is detached from the nicotinamide mononucleotide and is added to the 5,6-dimethylbenzimidazole, and thus one N-glycoside bond is replaced by a second N-glycoside bond (293,294). A variant of this enzyme (EC 2.4.2.55) has been characterized from the bacterium Sporomusa ovata.…”

Section: Reactions At the Anomeric Carbon Of Prppmentioning

confidence: 99%

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

Hove‐Jensen

Andersen

Kilstrup

et al. 2017

Microbiol Mol Biol Rev

157

187

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SUMMARY Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.

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“…On the basis of sequence homology to genes of known function in Pseudomonas denitrificans (for a recent review, see reference 2), it has been possible to assign functions to many of the genes in parts I and III of the cob operon. Mutations in the CobIII region have been analyzed genetically and biochemically, demonstrating that the cobU and cobS open reading frames correspond to part III of the genetic map (11,24,35). These two genes have been assigned the functions diagrammed in Fig.…”

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confidence: 99%

The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole

et al. 1995

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Salmonella typhimurium makes cobalamin (vitamin B 12 ) during anaerobic growth (17). Most of the cobalamin synthetic genes are organized into a single operon (cob or cbi) mapping at min 41 (3, 18). The genetic map of the cob operon can be divided into three distinct regions, each of which includes mutations with characteristic phenotypes. Part I has 17 genes (cbi) needed for cobinamide (Cbi) synthesis; strains with mutations in this region (CobI) can synthesize vitamin B 12 when Cbi is provided. Part II of the operon includes mutations that prevent vitamin B 12 synthesis unless 5,6-dimethylbenzimidazole (DMB) is provided (CobII), suggesting that this region contains the genes for DMB synthesis. Part III includes genes for joining Cbi and DMB to produce functional adenosyl-cobalamin (Ado-B 12 ); these mutants (CobIII) cannot make vitamin B 12 even when both DMB and Cbi are provided. The standard view of the pathway is depicted in Fig. 1.A fine-structure genetic map of the cob or cbi operon shows that the three types of mutations are ordered as parts I, III, and II in a single operon (3,18). The nucleotide sequences of parts I and III have been determined (27). On the basis of sequence homology to genes of known function in Pseudomonas denitrificans (for a recent review, see reference 2), it has been possible to assign functions to many of the genes in parts I and III of the cob operon. Mutations in the CobIII region have been analyzed genetically and biochemically, demonstrating that the cobU and cobS open reading frames correspond to part III of the genetic map (11,24,35). These two genes have been assigned the functions diagrammed in Fig.

show abstract

The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6-dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole, an intermediate in the synthesis of the nucleotide loop of cobalamin

Cited by 63 publications

References 21 publications

The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli

The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole

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