Cobalamin (vitamin B12) biosynthesis CobM/CbiF, precorrin-4 C11-methyltransferase (IPR006362)

Short name: Cbl_synth_CobM/CibF

Overlapping homologous superfamilies

Domain relationships

  • Tetrapyrrole methylase (IPR000878)
    • Cobalamin (vitamin B12) biosynthesis CobM/CbiF, precorrin-4 C11-methyltransferase (IPR006362)


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 CobM and CibF precorrin-4 C11-methyltransferase (EC:, both as stand-alone enzymes and when CobJ forms part of a bifunctional enzyme. In the aerobic pathway, CobM catalyses the methylation of precorrin-4 at C-11 to yield precorrin-5. The extruded acyl group is then removed in the subsequent step catalysed by CobF. In the anaerobic pathway, CibF catalyses the methylation of cobalt-precorrin-4 to cobalt-precoriin-5 [PMID: 11215515].

Nomenclature note: occasionally precorrin-4 C11-methyltransferase is one of two methyltransferases often referred to as precorrin-3 methylase (the other is precorrin-3 methylase (the other is precorrin-4 C11-methyltransferase, EC:

GO terms

Biological Process

GO:0009236 cobalamin biosynthetic process

Molecular Function

GO:0046026 precorrin-4 C11-methyltransferase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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