The biosynthesis of cobalamin (vitamin B-12) is described, revealing how th
e concerted action of around 30 enzyme-mediated steps results in the synthe
sis of one of Nature's most structurally complex 'small molecules'. The ple
thora of genome sequences has meant that bacteria capable of cobalamin synt
hesis can be easily identified and their biosynthetic genes compared. Where
as only a few years ago cobalamin synthesis was thought to occur by one of
two routes, there are apparently a number of variations on these two pathwa
ys, where the major differences seem to be concerned with the process of ri
ng contraction. A comparison of what is currently known about these pathway
s is presented. Finally, the process of cobalt chelation is discussed and t
he structure/function of the cobalt chelatase associated with the oxygen-in
dependent pathway (CbiK) is described.