Family

Cobalamin (vitamin B12) biosynthesis, bifunctional CbiH/CbiC (IPR014422)

Short name: Cbl_synth_bifunc_CbiH/CbiC

Overlapping homologous superfamilies

Family relationships

None.

Description

This entry represents a bifunctional enzyme of the cobalamin biosynthesis pathway. They contain both CbiH precorrin-3B C(17)-methyltransferase (EC:2.1.1.131, IPR006363) and CbiC precorrin-8X methylmutase (EC:5.4.1.2, IPR003722). CbiH catalyses the methylation of precorrin-3B at C-17 to produce precorrin-4. CbiC catalyses catalyses a methyl rearrangement in precorrin-8 that moves the methyl group from C-11 to C-12 to produce hydrogenobyrinic acid [PMID: 11470433].

CbiH belongs to the superfamily of tetrapyrrole (corrin/porphyrin) methylases (IPR000878), which includes methylases that use S-adenosylmethionine (S-AdoMet) in the methylation of diverse substrates. A number of other methylases in the cobalamin biosynthesis pathway also belong to this domain superfamily (precorrin-3 methylase, IPR012382, IPR012797, amongst others), and a fusion of precorrin-3B C17-methyltransferases with precorrin isomerase is represented by IPR014422.

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.

GO terms

Biological Process

GO:0009236 cobalamin biosynthetic process

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PIRSF