Biosynthesis of porphyrins and related macrocycles. Part 9. Biosynthesis of the corrin macrocycle of vitamin B12 including the stereochemistry of C-methylation in ring c

Abstract

Earlier work on the biosynthesis of vitamin B₁₂ is outlined; carbon-13 labelling coupled with n.m.r. spectroscopy is used for the current studies with Propionibacterium Shermanii. Growth of this organism, administration of precursors, and isolation of vitamin B₁₂ are described. Incorporation experiments with 5-amino[5-¹³C]laevulinic acid and with [methyl-¹³C]methionine confirm that the corrin macrocycle is constructed from eight molecules of 5-aminolaevulinic acid (one of which loses C-5) and seven methyl groups derived from methionine.

Degradation of the labelled vitamin B₁₂ derived from [methyl-¹³C] methionine proves that the pro-R methyl group at C-12 of ring c is the one derived from methionine. This result is confirmed by experiments with [methyl-²H₃]methionine which also establish that C-methylation at C-7 and C-1 2 of vitamin B₁₂ occurs by intact transfer of the S-methyl group from methionine.