Vitamin B12 is commercially produced using:
Vitamin B12, cobalamin, featuring corrin ring coordinating cobalt ion, requires approximately thirty enzymatic steps making chemical synthesis with 60 steps economically unviable, so industrial production entirely depends on microbial fermentation. Propionibacterium freudenreichii and Propionibacterium shermanii, propionic acid bacteria used in Swiss cheese ripening, synthesize active cobalamin via anaerobic pathway where cobalt inserted early into precorrin-2 by CbiK chelatase, distinct from aerobic Pseudomonas denitrificans pathway inserting cobalt late. Gene clusters cob and cbi encode methylation by CbiL, amidation, adenosyl attachment. Fermentation operates two-stage: initial anaerobic growth for corrin ring formation from uroporphyrinogen III via eight SAM-dependent methylations, followed by microaerobic phase for synthesis of lower ligand 5,6-dimethylbenzimidazole and attachment via CobT and CobS forming complete cobalamin. Supplementation with cobalt chloride 10 to 50 mg per L and DMBI precursor elevates yield. Finished product primarily adenosylcobalamin converted to cyanocobalamin by potassium cyanide treatment for stability, supporting global nutrition and feed supplementation. Modern fed-batch processes achieve cobalamin titers above 200 mg per L after 6 days under strict axenic conditions, with downstream purification involving heat-kill, filtration, ion exchange and crystallization delivering pharmaceutical grade purity required for injection and fortification.
Ref: Martens et al. Applied Microbiology Biotechnology 2002 Vitamin B12 fermentation; Lehninger Ch B-vitamin biosynthesis pathways.