Subsystem: Cobalamin synthesis
This subsystem's description is:
For more information, please check out the description and the additional notes tabs, below
Diagram | Functional Roles | Subsystem Spreadsheet | Additional Notes | |||||||||
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Anaerobic pathway adapted from proposal in: Roessner, C. A., Williams, H. J., Scott, A. I. 2005. Genetically Engineered Production of 1-Desmethylcobyrinic Acid, 1-Desmethylcobyrinic Acid a,c-Diamide, and Cobyrinic Acid a,c-Diamide in Escherichia coli Implies a Role for CbiD in C-1 Methylation in the Anaerobic Pathway to Cobalamin. J. Biol. Chem. 280: 16748-53. 5-aminolevulinic acid | | HemB | Porphobilinogne | | HemC | Hydroxymethylbilane | | HemD | Uroporphyrinogen III | | S-adenosyl-methionine |/ | CysG or CobA |\ | S-adenosyl-homocysteine | Precorrin 2 | | Co(2+) |/ | CysG or Sirohydrochlorin cobaltochelatase (EC 4.99.1.3) (CbiK) |\ | 2 H(+) | Cobalt-precorrin 2 | | S-adenosyl-methionine |/ | Cobalt-precorrin-2 C20-methyltransferase (EC 2.1.1.130) (CbiL) |\ | S-adenosyl-homocysteine | Cobalt-precorrin 3 = Cobalt-precorrin-3b | | S-adenosyl-methionine |/ | Cobalt-precorrin-3b C17-methyltransferase (CbiH) |\ | S-adenosyl-homocysteine | Cobalt-precorrin 4 | | S-adenosyl-methionine |/ | Cobalt-precorrin-4 C11-methyltransferase (CbiF) (EC 2.1.1.133) |\ | S-adenosyl-homocysteine | Cobalt-precorrin 5 | | S-adenosyl-methionine |/ | CbiD? |\ | S-adenosyl-homocysteine + Acetaldehyde | Cobalt-precorrin 6 = Cobalt-precorrin 6x | | NADPH, H+ |/ | Cobalt-precorrin-6x reductase (EC 1.3.1.54) (CbiJ) |\ | NADP+ | Dihydro-cobalt-precorrin 6 = Cobalt-precorrin 6y | | 2 S-adenosyl-methionine |/ | CbiE + CbiT (Cobalt-Precorrin 7 intermediate) |\ | 2 S-adenosyl-homocysteine + CO2 | Cobalt-precorrin 8 = Cobalt-precorrin 8x | | CbiC | Cobyrinic acid | | 2 glutamine |/ | CbiA |\ | 2 glutamate | Cob(II)yrinic acid a,c-diamide | | NADH + FMN |/ | Cobalt reductase | Cob(I)yrinic acid a,c-diamide | | ATP |/ | Cob(I)alamin adenosyltransferase (EC 2.5.1.17) (CobA or EutT or PduO) |\ | PPPi | Adenosyl-cobyrinic acid a,c-diamide | | 4 glutamine + 4 ATP |/ | Cobyric acid synthase (CbiP) |\ | 4 glutamate + 4 ATP + 4 Pi | Adenosyl-cobyrinc acid = Adenosyl-cobyrinic acid a,b,c,d,e,g-hexamide | | (R)-1-amino-2-propanol O-2-phosphate (see below) |/ | CbiB | Adenosyl-cobinamide phosphate | | GTP |/ | CobU |\ | PPi | Adenosyl-cobinamide-GDP | | alpha-ribozole (see below) |/ | CobS |\ | GMP | Adenosyl-cobalamin Keller et al. [Keller, J. P., Smith, P. M., Benach, J., Christendat, D., deTitta, G. T., Hunt, J. F. 2002. The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase. Structure (Camb) 10: 1475-87] suggest that CbiE methylates one site (probably C5) and CbiT methylates the other (probably C15), and that the C15 methylation destabilizes the acetyl group, which is lost with little or no additional enzymatic help. Alpha-ribazole: O'Toole, G. A., Trzebiatowski, J. R., and Escalante-Semerena, J. C. 1994. The cobC gene of Salmonella typhimurium codes for a novel phosphatase involved in the assembly of the nucleotide loop of cobalamin. J. Biol.0 Chem. 269: 26503-11. 5,6-dimethylbenzimidazole (DMB) | | Nicotinic acid mononucleotide |/ | Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21) (CobT) | Alpha-ribazole phosphate | | H2O |/ | Alpha-ribazole-5'-phosphate phosphatase (EC 3.1.3.73) (CobC) |\ | Pi | Alpha-ribazole = alpha-ribosyl-5,6-dimethylbenzimidazole (R)-1-amino-2-propanol O-2-phosphate: Brushaber, K. R., O'Toole, G. A., and Escalante-Semerena, J. C. 1998. CobD, a novel enzyme with L-threonine-O-3-phosphate decarboxylase activity, is responsible for the synthesis of (R)-1-amino-2-propanol O-2-phosphate, a proposed new intermediate in cobalamin biosynthesis in Salmonella typhimurium LT2. J. Biol. Chem. 273: 2684-91. L-threonine | | ATP |/ | ??? |\ | PPi | L-threonine-O-3-phosphate | | L-threonine-O-3-phosphate decarboxylase (CobD) |\ | CO2 | (R)-1-amino-2-propanol O-2-phosphate (CbiB substrate above) For unclear reasons, UniProt calls many instances of "L-threonine-O-3-phosphate decarboxylase" "Cobalamin biosynthesis protein CobC" (instead of CobD). The source of the confusion is not clear, but the function identification was in Salmonella, where the gene is CobD. CobU = Adenosylcobinamide-phosphate guanylyltransferase (EC 2.7.7.62) was originally thought to include Adenosylcobinamide kinase (EC 2.7.1.156) activity. The above pathway produces the phosphorylated form already, so the kinase activity is now removed from the annocation. |