How corrinoids are synthesized without oxygen: nature's first pathway to vitamin B12
By P.J.Santander, C. A.Roessner, N.J.Stolowich, M.T.Holderman, A. I. Scott, . Chem. Biol., 1997, 4(9), 659-666.

During the biosynthesis of vitamin B12, the aerobic bacterium Pseudomonas denitrificans uses 2 enzymes, CobG and CobJ, to convert precorrin-3 to the ring-contracted intermediate, precorrin-4.
CobG is a monooxygenase that adds an OH group, derived from O2, to C-20, whereas CobJ is bifunctional, inserting a Me group at C-17 of the macrocycle and catalyzing ring contraction.
O2 is not available to vitamin B12-producing anaerobic bacteria and members of the ancient Archaea, so the question arises of how these microbes accomplish the key ring-contraction process?
Cloning and overexpression of Salmonella typhimurium genes has led to the discovery that a single enzyme, CbiH, is responsible for ring contraction during anaerobic biosynthesis of vitamin B12. The process occurs when CbiH is incubated with precorrin-3, but only in the presence of cobalt. CbiH functions as a C-17 methyltransferase and mediates ring contraction and lactonization to yield the intermediate, Co-precorrin-4, isolated as Co-factor IV. 13C labeling studies have proved that Co-precorrin-4 is incorporated into cobyrinic acid, thereby confirming that Co-precorrin-4 is an intermediate in vitamin B12 biosynthesis.
Two distinct mechanisms exist in nature for the ring contraction of porphyrinoids to corrinoids - an ancient anaerobic pathway that requires cobalt complexation prior to nonoxidative rearrangement and a more recent aerobic route in which O2 serves as the cofactor.

  1. in anaerobes there is exchange of O2 at the C-27 acetate site, extrusion of acetaldehyde and early insertion of cobalt
  2. the aerobes show no exchange of O2 at C-27, extrude acetic acid, and insert cobalt very late in the biosynthetic pathway, after ring contraction has occurred.
There is thus a rationale for the main differences between aerobic and anaerobic biosynthesis of vitamin B12.