Anaerobic bacteria need their vitamin B ₁₂ to digest estrogen

Often described as nature’s most beautiful cofactor (1), vitamin B12 (cobalamin) is a complex and fascinating organometallic molecule that, although made only by some prokaryotes, has key functional roles in microbes, animals, and humans (2). Its two major biological forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), have a central cobalt atom in a corrin ring that is coordinated via a cobalt–carbon bond to an upper axial methyl or 5′-deoxyadenosyl group, respectively; in both forms the lower axial ligand is the 5,6-dimethylbenzimidazole (DMB) base of a nucleotide tail attached to the corrin ring (2⇓⇓–5). Finely controlled enzymatic or photolytic cleavage of the upper axial cobalt–carbon bond underlies the use of B12 as an enzyme cofactor or, in a new twist, as the light-sensing molecule in a photoreceptor protein (2⇓⇓–5). As an enzyme cofactor, MeCbl is used for methyl transfer reactions by methyltransferases and AdoCbl for radical-based transformations by mutases, dehydratases, deaminases, and ribonucleotide reductases (2⇓–4). In a broad range of organisms and biological processes, B12-dependent methyltransferases catalyze the transfer of a methyl group from a donor to a final acceptor, utilizing MeCbl or its methylcobamide analogs (with a base other than DMB) as methyl carriers. In these enzymes the nucleotide base in B12 is always displaced, often by a histidine ligand of a conserved DxHxxG protein motif (6⇓–8). Methionine synthase, a well-studied MeCbl-dependent methyltransferase present in many bacteria and mammals, is a single polypeptide with four modules that uses methyltetrahydrofolate as donor and homocysteine as acceptor to catalyze the terminal step in methionine biosynthesis (6, 7). In many microbes that thrive in anaerobic habitats, such as methanogens and acetogens, growth and energy production rely on B12-dependent methyltransferase systems that employ … [↵][1]1Email: melias{at}um.es. [1]: #xref-corresp-1-1