InterPro: IPR012798 Cobalamin (vitamin B12) biosynthesis CobG-like

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 [1]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase [2].

There are at least two distinct cobalamin biosynthetic pathways in bacteria [3]:

• Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [4]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.
• Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [5]; 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) [6]. 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 CobG from the aerobic pathway. CobG (precorrin-3b synthase, EC:1.14.13.83,) is a mono-oxygenase containing an iron-sulphur centre. CobG generates a gamma-lactone with the acetate side chain on ring A to give precorrin-3b. An oxygen atom from dioxygen is incorporated into the macrocycle at C-20. In the aerobic cobalamin biosynthesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. The first of the four steps is carried out by CobG, yielding precorrin-3B as the product. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ; EC:2.1.1.131), C-11 (CobM; EC:2.1.1.133) and C-1 (CobF; EC:2.1.1.152) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively.

This entry also contains ferredoxin-nitrite reductase (EC:2.1.1.152), a key enzyme in the process of nitrogen assimilation that makes use of a sirohaem-iron-sulphur cofactor [7].