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MetaCyc Pathway: adenosylcobalamin biosynthesis from cobyrinate a,c-diamide I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Vitamins Biosynthesis Cobalamin Biosynthesis

Some taxa known to possess this pathway include ? : Acidianus ambivalens , Propionibacterium freudenreichii shermanii , Pseudomonas denitrificans , Salmonella enterica enterica serovar Typhimurium

Expected Taxonomic Range: Archaea , Bacteria

Summary:
This pathway describes the late steps in the biosynthesis of vitamin B12 starting with cob(II)yrinate a,c-diamide - the step where the early-insertion and late-insertion pathways combine. In this pathway the lower ligand base of cobamides is tethered to the corrin ring via a structure known as the nucleotide loop, which is composed from (R)-1-amino-2-propanol O-2-phosphate and 5,6-dimethylbenzimidazole.

Until 2007 it was believed that the last reaction in the biosynthesis of coenzyme B12 was the linking of α-ribazole (a product of 5,6-dimethylbenzimidazole) to adenosylcobinamide-GDP, in a reaction catalyzed by cobalamine synthase (this view is described in adenosylcobalamin biosynthesis from cobyrinate a,c-diamide II). However, it has been shown that at least in Salmonella enterica enterica serovar Typhimurium the true substrate for the enzyme is α-ribazole 5'-phosphate, and not α-ribazole [Zayas07], and that the product of the reaction is actually adenosylcobalamin 5'-phosphate. Thus, there is one more reaction in the pathway, the dephosphorylation of adenosylcobalamin 5'-phosphate to coenzyme B12, which is catalyzed by α-ribazole-5'-phosphate phosphatase, the enzyme initially proposed to catalyze the dephosphorylation of α-ribazole 5'-phosphate [Zayas07].

This model addresses several questions that were associated with the previous model, such as the presence of adenosylcobalamin 5'-phosphate (which has been documented much earlier in the organism Propionibacterium freudenreichii shermanii [Friedmann68]), the higher affinity of the CobS protein (and its homologs in other organisms) towards α-ribazole 5'-phosphate, and the inability of cobC mutants to salvage cobyrate under aerobic conditions [Zayas07].

For more information, please see the summaries for the pathways adenosylcobalamin biosynthesis I (early cobalt insertion) and adenosylcobalamin biosynthesis II (late cobalt incorporation).

Superpathways: adenosylcobalamin biosynthesis I (early cobalt insertion) , adenosylcobalamin biosynthesis II (late cobalt incorporation)

Credits:
Created 23-Apr-2007 by Caspi R , SRI International


References

Friedmann68: Friedmann HC (1968). "Vitamin B 12 biosynthesis. Evidence for a new precursor vitamin B 12 5'-phosphate." J Biol Chem 243(8);2065-75. PMID: 4296474

Warren02: Warren MJ, Raux E, Schubert HL, Escalante-Semerena JC (2002). "The biosynthesis of adenosylcobalamin (vitamin B12)." Nat Prod Rep 19(4);390-412. PMID: 12195810

Zayas07: Zayas CL, Escalante-Semerena JC (2007). "Reassessment of the late steps of coenzyme B12 synthesis in Salmonella enterica: evidence that dephosphorylation of adenosylcobalamin-5'-phosphate by the CobC phosphatase is the last step of the pathway." J Bacteriol 189(6);2210-8. PMID: 17209023

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Blanche91a: Blanche F, Debussche L, Famechon A, Thibaut D, Cameron B, Crouzet J (1991). "A bifunctional protein from Pseudomonas denitrificans carries cobinamide kinase and cobinamide phosphate guanylyltransferase activities." J Bacteriol 1991;173(19);6052-7. PMID: 1655696

Blanche91b: Blanche F, Couder M, Debussche L, Thibaut D, Cameron B, Crouzet J (1991). "Biosynthesis of vitamin B12: stepwise amidation of carboxyl groups b, d, e, and g of cobyrinic acid a,c-diamide is catalyzed by one enzyme in Pseudomonas denitrificans." J Bacteriol 1991;173(19);6046-51. PMID: 1917839

Blanche92b: Blanche F, Maton L, Debussche L, Thibaut D (1992). "Purification and characterization of Cob(II)yrinic acid a,c-diamide reductase from Pseudomonas denitrificans." J Bacteriol 1992;174(22);7452-4. PMID: 1429467

Blanche95: Blanche F., Cameron B., Crouzet J., Debussche L., Thibaut D., Vuilhorgne M., Leeper F. J., Battersby A. R. (1995). "Vitamin B12: how the problem of its biosynthesis was solved." Angewandte Chemie. International edition in English 34(4): 383-411.

Cameron91: Cameron B, Blanche F, Rouyez MC, Bisch D, Famechon A, Couder M, Cauchois L, Thibaut D, Debussche L, Crouzet J (1991). "Genetic analysis, nucleotide sequence, and products of two Pseudomonas denitrificans cob genes encoding nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase and cobalamin (5'-phosphate) synthase." J Bacteriol 1991;173(19);6066-73. PMID: 1917841

Chen95a: Chen P, Ailion M, Weyand N, Roth J (1995). "The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole." J Bacteriol 177(6);1461-9. PMID: 7883701

Cheong01: Cheong CG, Escalante-Semerena JC, Rayment I (2001). "Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica." J Biol Chem 276(40);37612-20. PMID: 11441022

Cheong02a: Cheong CG, Escalante-Semerena JC, Rayment I (2002). "Structural studies of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica: the apo, substrate, and product-aldimine complexes." Biochemistry 41(29);9079-89. PMID: 12119022

Cheong99: Cheong CG, Escalante-Semerena JC, Rayment I (1999). "The three-dimensional structures of nicotinate mononucleotide:5,6- dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium complexed with 5,6-dimethybenzimidazole and its reaction products determined to 1.9 A resolution." Biochemistry 38(49);16125-35. PMID: 10587435

Crouzet90: Crouzet J, Cauchois L, Blanche F, Debussche L, Thibaut D, Rouyez MC, Rigault S, Mayaux JF, Cameron B (1990). "Nucleotide sequence of a Pseudomonas denitrificans 5.4-kilobase DNA fragment containing five cob genes and identification of structural genes encoding S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase and cobyrinic acid a,c-diamide synthase." J Bacteriol 172(10);5968-79. PMID: 2211520

Crouzet91: Crouzet J, Levy-Schil S, Cameron B, Cauchois L, Rigault S, Rouyez MC, Blanche F, Debussche L, Thibaut D (1991). "Nucleotide sequence and genetic analysis of a 13.1-kilobase-pair Pseudomonas denitrificans DNA fragment containing five cob genes and identification of structural genes encoding Cob(I)alamin adenosyltransferase, cobyric acid synthase, and bifunctional cobinamide kinase-cobinamide phosphate guanylyltransferase." J Bacteriol 173(19);6074-87. PMID: 1655697

Debussche91: Debussche L, Couder M, Thibaut D, Cameron B, Crouzet J, Blanche F (1991). "Purification and partial characterization of Cob(I)alamin adenosyltransferase from Pseudomonas denitrificans." J Bacteriol 1991;173(19);6300-2. PMID: 1917862

EscalanteSemere90: Escalante-Semerena JC, Suh SJ, Roth JR (1990). "cobA function is required for both de novo cobalamin biosynthesis and assimilation of exogenous corrinoids in Salmonella typhimurium." J Bacteriol 172(1);273-80. PMID: 2403541

Fonseca01: Fonseca MV, Escalante-Semerena JC (2001). "An in vitro reducing system for the enzymic conversion of cobalamin to adenosylcobalamin." J Biol Chem 276(34);32101-8. PMID: 11408479

Hsu05a: Hsu FC, Ho TJ, Lai CC, Lin CF, Chen HP (2005). "Cloning, sequencing, expression, and single-step purification of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) from Salmonella typhimurium ATCC 19585." Protein Expr Purif 42(1);178-81. PMID: 15939305

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lawrence08: Lawrence AD, Deery E, McLean KJ, Munro AW, Pickersgill RW, Rigby SE, Warren MJ (2008). "Identification, characterization, and structure/function analysis of a corrin reductase involved in adenosylcobalamin biosynthesis." J Biol Chem 283(16);10813-21. PMID: 18263579

Lawrence95: Lawrence JG, Roth JR (1995). "The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli." J Bacteriol 1995;177(22);6371-80. PMID: 7592411

MaggioHall04: Maggio-Hall LA, Claas KR, Escalante-Semerena JC (2004). "The last step in coenzyme B(12) synthesis is localized to the cell membrane in bacteria and archaea." Microbiology 150(Pt 5);1385-95. PMID: 15133100

MaggioHall99: Maggio-Hall LA, Escalante-Semerena JC (1999). "In vitro synthesis of the nucleotide loop of cobalamin by Salmonella typhimurium enzymes." Proc Natl Acad Sci U S A 96(21);11798-803. PMID: 10518530

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, BIOCYC14B.