The enzyme CobI then converts this to precorrin-3A: precorrin-2 + S-adenosyl methionine precorrin-3A + S-adenosyl-L-homocysteine From precorrin-3A to precorrin-3B Next, the enzyme CobG transforms precorrin-3A to precorrin-3B: precorrin-3A + NADH + H+ + O2 precorrin-3B + NAD+ + H2O This enzyme is an oxidoreductase that requires oxygen and hence the reaction can only operate under aerobic conditions. The naming of these precorrins as 3A and 3B reflects the fact that each contains three more methyl groups than uroporphyrinogen III but with different structures: in particular, precorrin-3B has an internal γ-lactone ring formed from the ring A acetic acid sidechain closing back on to the macrocycle. From precorrin-3B to precorrin-4 The enzyme CobJ continues the theme of methyl group insertion. Importantly, during this step the macrocycle ring-contracts so that the product contains for the first time the corrin core which characterises cobalamin. precorrin-3B + S-adenosyl methionine precorrin-4 + S-adenosyl-L-homocysteine From precorrin-4 to precorrin-5 Methyl group insertions continue as the enzyme CobM acts on precorrin-4: precorrin-4 + S-adenosyl methionine precorrin-5 + S-adenosyl-L-homocysteine The newly-inserted methyl group is added to ring C at the carbon attached to the methylene (CH2) bridge to ring B. This is not its final location on cobalamin as a later step involves its rearrangement to an adjacent ring carbon. From precorrin-5 to precorrin-6A The enzyme CobF now removes the acetyl group located at position 1 of the ring system in precorrin-4 and replaces it with a newly-introduced methyl group. The name of the product, precorrin-6A, reflects the fact that six methyl groups in total have been added to uroporphyrinogen III up to this point. However, since one of these has been extruded with the acetate group, the structure of precorrin-6A contains just the remaining five. precorrin-5 + S-adenosyl methionine + H2O precorrin-6A + S-adenosyl-L-homocysteine + acetate From precorrin-6A to precorrin-6B The enzyme CobK now reduces a double bond in ring D using NADPH: precorrin-6A + NADPH + H+ precorrin-6B + NADP+ Precorrin-6B therefore differs in structure from precorrin-6A only by having an extra two hydrogen atoms. From precorrin-6B to precorrin-8 The enzyme CobL has two active sites, one catalysing two methyl group additions and the other the decarboxylation of the CH2COOH group on ring D, so that this substituent becomes a simple methyl group: precorrin-6B + 2 S-adenosyl methionine precorrin-8X + 2 S-adenosyl-L-homocysteine + CO2 From precorrin-8 to hydrogenobyrinic acid The enzyme CobH catalyzes a rearrangement reaction, with