Family

Cobalamin (vitamin B12) biosynthesis CobF, precorrin-6A synthase (IPR012797)

Short name: Cbl_synth_CobF

Overlapping homologous superfamilies

Family relationships

None.

Description

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 CobF precorrin-6A synthase (EC:2.1.1.152), a pathway-specific enzyme in the aerobic pathway. After precorrin-4 is methylated at C-11 by CobM to produce precorrin-5, the extruded acyl group is then removed in the subsequent step, which also sees a methyl group added at C-1 in a reaction catalysed by CobF. The product of this reaction is precorrin-6A, which is subsequently reduced by an NADH-dependent reductase to precorrin-6B [PMID: 11215515]. This entry identifies CobF in high GC Gram-positive, alphaproteobacteria and pseudomonas-related species.

GO terms

Biological Process

GO:0009236 cobalamin biosynthetic process

Molecular Function

GO:0043819 precorrin-6A synthase (deacetylating) activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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