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 → Adenosylcobalamin Biosynthesis → Adenosylcobalamin Biosynthesis from Cobyrinate Diamide|
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 adenosylcobalamin 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 adenosylcobalamin, 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].
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
Blanche91a: 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
Blanche91b: 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
Blanche92: 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
Chen95: 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
Cheong02: 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
Hsu05: 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
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
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
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