Cobalamin biosynthesis

In both cases, the macrocycle that will form a coordination complex with the cobalt ion is a corrin ring, specifically one with seven carboxylate groups called cobyrinic acid.

In the final part of the biosynthesis, common to all organisms, an aminopropanol sidechain is added to the one free carboxylic group and assembly of the nucleotide loop, which will provide the second ligand for the cobalt, is completed.

It consists of a modified tetrapyrrole, a corrin, with a centrally chelated cobalt ion and is usually found in one of two biologically active forms: methylcobalamin and adenosylcobalamin.

In bacteria and archaea, these enzymes include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia-lyase, and diol dehydratase.

[5] Species from the following genera and the following individual species are known to synthesize cobalamin: Propionibacterium shermanii, Pseudomonas denitrificans, Streptomyces griseus, Acetobacterium, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Lactobacillus, Micromonospora, Mycobacterium, Nocardia, Proteus, Rhizobium, Salmonella, Serratia, Streptococcus and Xanthomonas.

[14][15] In the early steps of the biosynthesis, a tetrapyrrolic structural framework is created by the enzymes deaminase and cosynthetase which transform aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III.

It was not until scientists at Rhône-Poulenc Rorer used a genetically-engineered strain of Pseudomonas denitrificans, in which eight of the cob genes involved in the biosynthesis of the vitamin had been overexpressed, that the complete sequence of methylation and other steps could be determined, thus fully establishing all the intermediates in the pathway.

Many of the steps beyond uroporphyrinogen III in anaerobic organisms such as Bacillus megaterium involve chemically similar but genetically distinct transformations to those in the aerobic pathway.

The introduction of the methyl group at C-11 in the next step is catalysed by Cobalt-precorrin-4 methyltransferase (CbiF, EC 2.1.1.271)[29] The scene is now set for the extrusion of the two-carbon fragment corresponding to the acetate released in the formation of precorrin-6A in the aerobic pathway.

In this case the fragment released is acetaldehyde and this is catalysed by CbiG:[29] The steps from cobalt-precorrin-5B to cob(II)yrinic acid a,c-diamide in the anaerobic pathway are essentially chemically identical to those in the aerobic sequence.

Methylmalonic aciduria and homocystinuria type C protein is the enzyme which catalyzes the decyanation of cyanocobalamin as well as the dealkylation of alkylcobalamins including methylcobalamin and adenosylcobalamin.