Pathways & interactions
Cobalamin (vitamin B12) biosynthesis CbiE, precorrin-6Y methyltransferase (IPR012818)
Short name: Cbl_synth_CbiE
Overlapping homologous superfamilies
- Tetrapyrrole methylase superfamily (IPR035996)
- Tetrapyrrole methylase (IPR000878)
- Cobalamin (vitamin B12) biosynthesis CbiE, precorrin-6Y methyltransferase (IPR012818)
Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [PMID: 12869542]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase [PMID: 17163662].
There are at least two distinct cobalamin biosynthetic pathways in bacteria [PMID: 11153269]:
- Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [PMID: 16042605]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.
- Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [PMID: 12055304, PMID: 23922391]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii.
Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [PMID: 11215515]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans.
This entry represents CbiE subunit of precorrin-6Y C5,15-methyltransferase (EC:126.96.36.199) from the anaerobic pathway, a bifunctional enzyme that catalyses two methylations (at C-5 and C-15) in precorrin-6Y, as well as the decarboxylation of the acetate side chain located in ring C, in order to generate precorrin-8X. In the anaerobic pathway, two enzymes are required to produce precorrin-8X: CbiE and CbiT, which can be fused as CbiET (sometimes called CobL) [PMID: 12429089]. In the aerobic pathway, the bifunctional enzyme is CobL [PMID: 1732195].