Vitamin B12 Industrial Production PDF

Vitamin B12 Industrial Production  Vitamin B Vitamin B12, also known as cyanocobalamin, belongs to the 12 cobalamin family of compounds, which are composed of a corrinoid ring and an upper and lower ligand. The u...

Vitamin B12 Industrial Production  Vitamin B Vitamin B12, also known as cyanocobalamin, belongs to the 12 cobalamin family of compounds, which are composed of a corrinoid ring and an upper and lower ligand. The upper ligand can be adenosine, methyl, hydroxy, or a cyano group. Vitamin B12 (cyanocobalamin) is a water soluble vitamin with disease,pernicious The complex structure. The empirical anemia, formula of characterized cyanocobalamin by low hemoglobin, is C63Hof levels decreased90N14O14PCo. number of erythrocytes and neurological manifestations, has been known for several decades. It was in 1926someworkers reported the liver extracts couldcure pernicious anemia. The active principle was later identified as vitamin B12, a water soluble B- complex vitamin. Vitamin B12 is exclusively synthesized in nature by microorganisms. Vitamin B12 is synthesized by prokaryotes and inhibits the  Commercial Production of Vitaminfirst Vitamin B12obtained asa byproduct B1 fermentation was in of the production Streptomyces of certain antibiotics 2 (streptomycin, chloramphenicol, or neomycin). – But the yield was very low. Later, high-yielding strains were developed. It is estimated that the world’s annual production of vitamin B12 is around 15,000 kg. High concentrations of vitamin B12 are detected in sewage-sludge solids. This is produced by microorganisms. Recovery of vitamin B12 from sewage-sludge was carried out in some parts of United States. Unlike most other vitamins, the chemical synthesis of vitamin B12 is not practicable, since about 20 complicated reaction steps need to be carried out.  Microorganisms and Yields of Vitamin B12 The natural process of vitB12 synthesis by approximately 30 enzyme mediated steps. Several microorganisms can be employed for the production of vitamin B12, with varying yields. Glucose is the most commonly used carbon source. Some examples of microbes and their corresponding yields are given in Table 1. The most commonly used microorganisms are — – Propionibacterium freudenreichii, – Pseudomonas denitrificans, – Bacillus megaterium – Streptomyces olivaceus  Production of Vitamin B12 Using Propionibacterium Propionibacterium sp. and their freudenreichii and P. shermanii, mutant strains are commonly used for vitamin B12 production. The process is carried out by adding cobalt in two phases. Anaerobic phase: This is a preliminary phase that may take 2-4 days. In this phase 5′-deoxyadenosylcobinamide is predominantly produced. Aerobic phase: In this phase, 5, 6-dimethyl- Benz imidazole is produced from riboflavin which gets incorporated to finally form coenzyme of vitamin namely 5′- deoxyadenosylcobalamin. In recent years, some fermentation technologists have successfully clubbed both an anaerobic and aerobic phases to carry The out theproduction bulk operation continuously of vit in two is reaction mostlytanks. B1 done by submerged fermentation bacterial with beet molasses medium supplemented with 2 cobalt chloride. The specific details of the process are kept as  Recovery of vitamin The cobalamins B12by fermentation produced are mostly bound to the cells. They can be solubilized by heat treatment at 80- 120°C for about 30 minutes at pH 6.5-8.5. The solids and mycelium are filtered or centrifuged and the fermentation broth collected. The cobalamins can be converted to more stable cyanocobalamins. This vitamin B12 is around 80% purity and can be directly used as a feed additive. However, for medical use (particularly for treatment of pernicious anemia), vitamin B12 should be further purified (95-98% purity).  Production of Vitamin B12 using Pseudomonas Pseudomonas denitrificans is sp. also used for large scale production of vitamin B12 in a cost-effective manner. Starting with a low yield (0.6 mg/l) two decades ago, several improvements have been made in the strains of P. denitrificans for a tremendous improvement in the yield (60 mg/l). Addition of cobalt and 5, 6-dimethyl Benz imidazole to the medium is essential. The yield of vitamin B12 increases when the  Carbon Sources for Vitamin B12 Production Glucose is the most commonly used carbon source for large scale manufacture Other carbon of vitamin lik B12alcoho. (methan ethanol, sources isopropanol)e and ls hydrocarbons ol, (alkanes, decane, hexadecane) with varying yields can also be used. A yield of 42 mg/l of vitamin B12 was reported using methanol as the carbon source by the microorganism Methanosarcina barkeri, in fed- batch culture system.