Vitamin B12 - Synthesis and Industrial Production

Synthesis and Industrial Production

Neither plants nor animals are independently capable of constructing vitamin B₁₂. Only bacteria and archaea have the enzymes required for its biosynthesis. The total synthesis of B₁₂ was reported by Robert Burns Woodward and Albert Eschenmoser in 1972, and remains one of the classic feats of organic synthesis. Species from the following genera are known to synthesize B₁₂: Acetobacterium, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Lactobacillus, Micromonospora, Mycobacterium, Nocardia, Propionibacterium, Protaminobacter, Proteus, Pseudomonas, Rhizobium, Salmonella, Serratia, Streptomyces, Streptococcus and Xanthomonas.

Industrial production of B₁₂ is through fermentation of selected microorganisms. Streptomyces griseus, a bacterium once thought to be a yeast, was the commercial source of vitamin B₁₂ for many years. The species Pseudomonas denitrificans and Propionibacterium shermanii are more commonly used today. These are frequently grown under special conditions to enhance yield, and at least one company, Rhône-Poulenc of France, which has merged into Sanofi-Aventis, used genetically engineered versions of one or both of these species. Since a number of species of Propionibacterium produce no exotoxins or endotoxins and are generally regarded as safe (have been granted GRAS status) by the Food and Drug Administration of the United States, they are presently the FDA-preferred bacterial fermentation organisms for vitamin B₁₂ production.

The total world production of vitamin B₁₂, by four companies (the French Sanofi-Aventis and three Chinese companies) is said to have been 35 tonnes in 2008. Most of this production is used as an additive to animal feed.

See cyanocobalamin for discussion of the chemical preparation of reduced-cobalt vitamin analogs and preparation of physiological forms of the vitamin such as adenosylcobalamin and methylcobalamin.