Generic placeholder image

Current Nutrition & Food Science


ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Review Article

Vitamin B12: From Deficiency to Biotechnological Solution

Author(s): Ramona Massoud, Kianoush Khosravi-Darani*, Seyed M.H. Bagheri, Amir M. Mortazavian and Sara Sohrabvandi

Volume 15, Issue 4, 2019

Page: [318 - 326] Pages: 9

DOI: 10.2174/1573401314666171207145429

Price: $65


Vitamin B12 production by using propionibacteria and enriching food to produce functional foods is an important subject for researches. Some microorganisms have the potential to produce a wide range of components that are health promoting for human. Among them Propionibacteria has been identified as an effective producer of vitamin B12 and anti-microbial compounds such as propionic acid for decades. In this study at first, the structure, health beneficial effects and properties of vitamin B12 as well as scaled up production of vitamin are mentioned. Then biotechnological strategy is described as a solution to overcome vitamin deficiency and production of functional food. Finally, the specification of propionibacteria and its growth condition as well as bacterium ability to produce some other interesting metabolite in human food as byproduct are discussed.

Keywords: Biosynthesis, functional food, health effects, propionibacteria, vitamin B12, anti-microbial compounds.

Graphical Abstract
Zhang A. Metabolic engineering and process development for enhanced propionic acid production by Propionibacterium acidipropionici. PhD dissertation. Ohio State University 2009
Li KT, Liu DH, Chu J, Wang YH, Zhuang YP, Zhang SL. An effective and simplified pH-stat control strategy for the industrial fermentation of vitamin B12 by Pseudomonas denitrificans. Bioprocess Biosyst Eng 2008; 31(6): 605-10. a
Demain AL, Daniels HJ, Schnable L, White RF. Specificity of the stimulatory effect of betaine on the vitamin B12 fermentation. Nature 1968; 220: 1324-33.
Hugenholtz J, Hunik J, Santos H, Smid E. Nutraceutical production by propionibacteria. Le Lait 2002; 82(1): 103-12.
Sánchez Tainta A, Zazpe I, Bes-Rastrollo M, Salas-Salvadó J, Bullo M, Vicente Sorlí J. Nutritional adequacy according to carbohydrates and fat quality. Eur J Nutr 2016; 55: 93-106.
Yongsmith B, Sonomoto K, Tanaka A, Fukui S. Production of vitamin B12 by immobilized cells of a propionic acid bacterium. Eur J Appl Microbiol 1982; 6(2): 70-4.
Kamikubo T, Hayashi M, Nishio N, Nagai S. Utilization of non-sugar sources for vitamin B12 production. Appl Environ Microbiol 1978; 35(5): 971-3.
Selvakumar P, Balamurugan G, Viveka S. Microbial production of vitamin B12 and antimicrobial activity of glucose utilizing marine derived Streptomyces species. Int J Chemtech Res 2012; 4(3): 236-42.
Wang P, Wang Y, Su Z. Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor. Bioresour Technol 2012; 104: 652-9.
Quesada-Chanto A, Afschar A, Wagner F. Optimization of a Propionibacterium acidipropionici continuous culture utilizing sucrose. Appl Microbiol Biotechnol 1994; 42(1): 16-21. a
Quesada-Chanto A, Wagner F. Microbial production of propionic acid and vitamin B12 using molasses or sugar. Appl Microbiol Biotechnol 1994; 41(4): 378-83. b
Kośmider A, Białas W, Kubiak P, Drożdżyńska A, Czaczyk K. Vitamin B12 production from crude glycerol by Propionibacterium freudenreichii ssp shermanii: Optimization of medium composition through statistical experimental designs. Bioresour Technol 2012; 105: 128-33.
Bullerman L, Berry E. Use of cheese whey for vitamin B12 production whey solids and yeast extract levels. Appl Microbiol 1966; 14(3): 353-5.
Combe JS. History of a case of anaemia. Trans Med Soc Edinb 1824; 1: 194-204.
Whipple G, Robscheit-Robbins F. Blood regeneration in severe anemia. Am J Physiol 1925; 72(3): 395-407.
Minot GR, Murphy WP. Treatment of pernicious anemia by a special diet. JAMA 1983; 250(24): 3328-35.
Schneider Z. Stroinski A Comprehensive B12: Chemistry, biochemistry, nutrition, ecology, medicine. Walter de Gruyter New York 2011; pp. 165-78.
Escalante-Semerena JC. Conversion of cobinamide into adenosylcobamide in bacteria and archaea. J Bacteriol 2007; 189(13): 4555-60.
Roth JR, Lawrence JG, Rubenfield M, Kieffer-Higgins S, Church GM. Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. J Bacteriol 1993; 175(11): 3303-16.
Roth J, Lawrence J, Bobik T. Cobalamin (coenzyme B12): Synthesis and biological significance. Annu Rev Microbiol 1996; 50(1): 137-81.
Fan C, Bobik TA. The PduX enzyme of Salmonella enterica is an L-threonine kinase used for coenzyme B12 synthesis. J Biol Chem 2008; 283(17): 11322-9.
Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS. Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes. J Biol Chem 2008; 278(42): 41148-59.
Thoden JB, Holden HM. Molecular structure of galactokinase. J Biol Chem 2008; 278(35): 33305-11.
Xia W, Chen W, Peng W, Li K. Industrial vitamin B12 production by Pseudomonas denitrificans using maltose syrup and corn steep liquor as the cost-effective fermentation substrates. Bioprocess Biosyst Eng 2015; 38: 1065-73.
Marwaha S, Sethi R, Kennedy J. Role of amino acids betaine and choline in vitamin B12 biosynthesis by strains of Propionibacterium. Enzyme Microb Technol 1983; 5(6): 454-6.
Vandamme EJ. Production of vitamins coenzymes and related biochemicals by biotechnological processes. J Chem Technol Biotechnol 1992; 53(4): 313-27.
Rickes EL, Brink NG, Koniuszy FR, Wood TR, Folkers K. Crystalline vitamin B12. Science 1948; 107(27): 396-7.
Smith EL. Purification of anti-pernicious anaemia factors from liver. Nature 1948; 161(40): 638-42.
Hartley A, Glynn SE, Barynin V, et al. Substrate Specificity and Mechanism from the Structure of Pyrococcus furiosus Galactokinase. J Mol Biol 2004; 337(2): 387-8.
Thoden JB, Timson DJ, Reece RJ, Holden HM. Molecular structure of human galactokinase implications for type II galactosemia. J Biol Chem 2005; 280(10): 9662-70.
Zhou T, Daugherty M, Grishin NV, Osterman AL, Zhang H. Structure and mechanism of homoserine kinase: Prototype for the GHMP kinase superfamily. Structure 2000; 8(12): 1247-57.
Krishna SS, Zhou T, Daugherty M, Osterman AL, Zhang H. Structural basis for the catalysis and substrate specificity of homoserine kinase. Biochem 2001; 40(36): 10810-8.
Andreassi JL, Bilder PW, Vetting MW, Roderick SL, Leyh TS. Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate. Protein Sci 2007; 16(5): 983-9.
Fu Z, Wang M, Potter D, Miziorko HM, Kim JJP. The structure of a binary complex between a mammalian mevalonate kinase and ATP insights into the reaction mechanism and human inherited disease. J Biol Chem 2002; 277(20): 18134-42.
Sgraja T, Smith TK, Hunter WN. Structure substrate recognition and reactivity of Leishmania major mevalonate kinase. BMC Struct Biol 2007; 7(1): 20-4.
Yang D, Shipman LW, Roessner CA, Scott AI, Sacchettini JC. Structure of the Methanococcus jannaschii mevalonate kinase a member of the GHMP kinase superfamily. J Biol Chem 2002; 277(11): 9462-7.
Lindsay H. Vitamin B12. Adv Nutr 2012; 3: 54-5.
Chamlagain B, Deptula P, Edelmann M, Kariluoto S. Effect of the lower ligand precursors on vitamin B12 production by food-grade Propionibacteria. Food Sci Technol 2016; 72: 117-24.
Martens JH, Barg H, Warren M, Jahn D. Microbial production of vitamin B12. Appl Microbiol Biotechnol 2002; 58(3): 275-85.
Cook Campanello G, Twahir U, Brunold T, Warncke K, Banerjee R. Labilization of the cobalt-carbon bond in vitamin B12 bound to adenosyltransferase. FASEB J 2017; 31: 603-16.
Kozyraki R, Cases O. Vitamin B12 absorption: Mammalian physiology and acquired and inherited disorders. Biochimie 2013; 95: 1002-7.
Stabler SP. Vitamin B12 deficiency. N Engl J Med 2013; 368: 149-60.
Shweta AS, Kumar Gupta SP, Singh A, Teja V. Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin. Acta Biomater 2016; 31: 288-300.
Miller N, Wiley TE, Spears KG, et al. Toward the design of photoresponsive conditional antivitamins B12: A Transient absorption study of an arylcobalamin and an alkynylcobalamin. J Am Chem Soc 2016; 138(43): 14250-6.
Woo K, Kwok T, Celermajer DS. Vegan diet subnormal vitamin B12 status and cardiovascular health. Nutrients 2014; 6(8): 3259-73.
Moll R, Davis B. Iron vitamin B12 and folate. Medicine 2017; 45(4): 198-203.
Vakur Bor M, Mavon K, Gail R, et al. Daily intake of 4 to 7 μg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr 2010; 91(3): 571-7.
Herbert V. Recommended dietary intakes (RDI) of vitamin B-12 in humans. Am J Clin Nutr 1987; 45(4): 671-8.
Bae S, West AA, Yan J, et al. Vitamin B-12 status differs among pregnant lactating and control women with equivalent nutrient intakes. J Nutr 2015; 145(7): 1507-14.
Eitenmiller RR, Landen WO, Lye J. Vitamin analysis for the health and food sciences. 2nd ed. CRC press: New York 2008.
Ekaterina M, Zhang M, Daniel J, Karen W. Phinney C, Pfeiffer M. An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys. Anal Bioanal Chem 2015; 407(11): 2955-64.
Obeid R, Geisel J, Herrmann W. Comparison of two methods for measuring methylmalonic acid as a marker for vitamin B12 deficiency. Diagnosis 2015; 1: 24.
Peggy A, Domstad MD, Young C, et al. Reliability of the dual-isotope schilling test for the diagnosis of pernicious anemia or malabsorption syndrome. Am J Clin Pathol 1981; 75(5): 723-6.
David O, Kennedy B. Vitamins and the brain: Mechanisms dose and efficacy—a review. Nutrients 2016; 8(2): 68-72.
Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ 2014; 34: 52-6.
Andrès E, Loukili H, Georges EN, Maher K, et al. Vitamin B12 (cobalamin) deficiency in elderly patients Canadian Medical Association or its licensors. CMAJ 2004; 171(3): 251-9.
Liljeberg H, Björck I. Delayed gastric emptying rate as a potential mechanism for lowered glycemia after eating sourdough bread: Studies in humans and rats using test products with added organic acids or an organic salt. Am J Clin Nutr 1996; 64(6): 886-93.
Cherbut C, Ferrier L, Rozé C, Anini Y, et al. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am J Physiol Gastrointest Liver Physiol 1998; 275(6): 1415-22.
Dockray G. Gut endocrine secretions and their relevance to satiety. Curr Opin Pharmacol 2004; 4(6): 557-60.
Bomba A, Nemcová R, Mudroňová D, Guba P. The possibilities of potentiating the efficacy of probiotics. Trends Food Sci Technol 2002; 13(4): 121-6.
Ekinci F, Gurel M. Effect of using propionic acid bacteria as an adjunct culture in yogurt production. J Dairy Sci 2008; 91(3): 892-9.
Remacha A, Zapico E, Sarda M, et al. Immune complexes and persistent high levels of serum vitamin B12. Int J Lab Hematol 2014; 36(1): 92-7.
Hara H, Haga S, Aoyama Y, Kiriyama S. Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine. J Nutr 1999; 129(5): 942-8.
Goldman B, Roth J. Genetic structure and regulation of the cysG gene in Salmonella typhimurium. J Bacteriol 1993; 175(5): 1457-66.
Raux E, Schubert HL, Roper JM, Wilson KS, Warren MJ. Vitamin B12: Insights into biosynthesis’s mount improbable. Bioorg Chem 1999; 27(2): 100-18.
Raux E, Thermes C, Heathcote P, Rambach A, Warren MJ. A role for Salmonella typhimurium cbiK in cobalamin (vitamin B12) and siroheme biosynthesis. J bacterial 1997; 179(10): 3202-12.
Banerjee R. Chemistry and Biochemistry of B12. John Wiley and Sons London 1999.
Eschenmoser A, Wintner CE. Natural product synthesis and vitamin B12. Science 1977; 196: 1410-20.
Woodward RB. The total synthesis of vitamin B12. Pure Appl Chem 1973; 33: 17-20.
Martens JH, Barg H, Warren M, Jahn D. Microbial production of vitamin B12. Appl Microbiol Biotechnol 2002; 58(3): 275-85.
Biedendieck R, Malten M, Barg H, et al. Metabolic engineering of cobalamin (vitamin B12) production in Bacillus megaterium. Microb Biotechnol 2010; 3(1): 24-37.
Santos F, Teusink B, Molenaar D. Effect of amino acid availability on vitamin B12 production in Lactobacillus reuteri. Appl Environ Microbiol 2009; 75(12): 3930-6.
Madhu AN, Giribhattanavar P, Narayan MS, Prapulla SG. Probiotic lactic acid bacterium from kanjika as a potential source of vitamin B12: Evidence from LC-MS. Immunol Microbial Tech Biotechnol Letters 2010; 32(4): 503-6.
Wang ZJ, Wang P, Chu J, Zhang SL. Optimization of nutritional requirements and ammonium feeding strategies for improving vitamin B12 production by Pseudomonas denitrificans. Afr J Biotechnol 2011; 10(51): 10551-61.
Bykhovsky VY, Zaitseva N, Eliseev A. Tetrapyrroles: Diversity biosynthesis and biotechnology. (Review) Appl Biochem Microbiol 1998; 34(1): 1-18.
Blanche F, Cameron B, Crouzet J, et al. Vitamin B12: wie das problem seiner biosynthese gelöst wurde. Angew Chem 1995; 107(4): 421-52.
Pawelkiewicz J, Zodrow K. Biosynthesis of cobalamin compounds II Mechanism of cobalamin formation in Corynebacterium diphtheria. Acta Biochim Pol 1957; 4(3): 203-8.
Hendlin D, Ruger ML. The effect of cobalt on the microbial synthesis of LLD-active substances. Science 1950; 111: 541-2.
Pawlak R, Lester SE, Babatunde T. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: A review of literature. Eur J Clin Nutr 2014; 5: 41-8.
LeBlanc J, Milani C, Giori G, Sesma F, Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: A gut microbiota perspective. Curr Opin Biotechnol 2013; 24: 160-8.
Eggersdorfer M, Adam G, John M. Ullmann’s Encyclopedia of Industrial Chemistry VCH. Weinheim, Germany 1995.
Regnell O, Tunlid A, Ewald G, Sangfors O. Methyl mercury production in freshwater microcosms affected by dissolved oxygen levels: Role of cobalamin and microbial community composition. Can J Fish Aquat Sci 1996; 53: 1535-45.
Spalla C, Grein A, Garofano L, Ferni G. Microbial production of vitamin B12 in Biotechnology of vitamins pigments and growth factors. Elsevier Applied Science New York 1989; pp. 175-80.
Soheili M, Khosravi-Darani K. The potential health benefits of algae and micro algae in medicine: A review on Spirulina platensis. Curr Nutr Food Sci 2011; 7(4): 279-85.
Mazinani S, Fadaei V, Khosravi-Darani K. Impact of Spirulina platensis on physicochemical properties and viability of Lactobacillus acidophilus of probiotic UF Feta cheese. J Food Process Preserv 2016; 40(6): 1318-24.
Marzieh Hosseini S, Shahbazizadeh S, Khosravi-Darani K, Mozafari MR. Spirulina paltensis: Food and function. Curr Nutr Food Sci 2013; 9(3): 189-93.
Beheshtipour H, Mortazavian AM, Mohammadi R, Sohrabvandi S, Khosravi-Darani K. Supplementation of Spirulina platensis and Chlorella vulgaris algae into probiotic fermented milks. Compr Rev Food Sci Food Saf 2013; 12(2): 144-54.
Massoud R, Khosravi-Darani K, Nakhsaz F, Varga L. Evaluation of physico-chemical, microbiological and sensory properties of croissants fortified with Arthrospira platensis (Spirulina). Czech J Food Sci 2015; 34(4): 350-5.
Kumudha A, Sarada R. Effect of different extraction methods on vitamin B12 from blue green algae, Spirulina Platensis. Pharm Anal Acta 2015; 6: 337.
K Khosravi-Darani. Research activities on supercritical fluid science in food biotechnology. Crit Rev Food Sci Nutr 2010; 50(6): 479-88.
Khosravi-Darani K, Vasheghani-Farahani E. Application of supercritical fluid extraction in biotechnology. Crit Rev Biotechnol 2005; 25: 1-12.
Khalilovaa E, Nuratinovb R, Kotenkoa C, Islammagomedovaa E. Hydrocarbon oxidizing microorganisms of hot springs and their significance in the assessment of the biodiversity of microbial. Commun Arid Ecosys 2014; 4(1): 25-30.
Tharmaraj N, Shah N. Selective enumeration of Lactobacillus delbrueckii ssp bulgaricus Streptococcus thermophiles, Lactobacillus acidophilus, Bifidobacteria, Lactobacillus casei, Lactobacillus rhamnosus, and Propionibacteria. J Dairy Sci 2003; 86(7): 2288-96.
Sheehan JJ, Wilkinson MG, McSweeney PL. Influence of processing and ripening parameters on starter non-starter and propionic acid bacteria and on the ripening characteristics of semi-hard cheeses. Int Dairy J 2008; 18(9): 905-17.
Coral J, Karp SG, De Souza Vandenberghe LP, Parada JL, Pandey A, Soccol CR. Batch fermentation model of propionic acid production by Propionibacterium acidipropionici in different carbon sources. Appl Biochem Biotechnol 2008; 151(2): 333-4.
Wang Shang Z, Yang T. Propionic acid production in glycerol/glucose co-fermentation by Propionibacterium freudenreichii subsp Shermanii. Bioresour Technol 2013; 137: 116-23.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy