Absolute stereochemistry of precorrin-3x and its relevance to the dichotomy of ring contraction mechanism in vitamin B-12 biosynthesis

In Nature, two pathways of vitamin B-12 biosynthesis have been discovered. In the aerobe Pseudomonas denitrificans molecular oxygen is utilized in the formation of the novel hydroxy-gamma-lactone intermediate precorrin-3x. In the subsequent conversion of precorrin-3x to hydrogenobyrinic acid catalyzed by the Ps. denitrificans Cob enzymes, we demonstrate that no oxygen exchange of the peripheral carboxylic acid functions with the medium takes place. This result is in sharp contrast to the anaerobic pathway in Propionibacterium shermanii, where a unique carboxylate function (ring A acetate) undergoes extensive oxygen exchange. The stereochemistry of precorrin-3x at the C-20 center was determined using NMR and it is proposed that the C-20 hydroxyl is cis to the oxygen terminus of the gamma-lactone at C-1, a result that has a distinct bearing on the ring contraction mechanism of corrin biosynthesis in Ps. denitrificans. The implications of these findings for both the aerobic and anaerobic pathways are discussed and two discrete mechanisms for ring contraction and the subsequent loss of acetic acid are presented.