Tagatose: properties, applications, and biotechnological processes



d-Tagatose has attracted a great deal of attention in recent years due to its health benefits and similar properties to sucrose. d-Tagatose can be used as a low-calorie sweetener, as an intermediate for synthesis of other optically active compounds, and as an additive in detergent, cosmetic, and pharmaceutical formulation. Biotransformation of d-tagatose has been produced using several biocatalyst sources. Among the biocatalysts, l-arabinose isomerase has been mostly applied for d-tagatose production because of the industrial feasibility for the use of d-galactose as a substrate. In this article, the characterization of many l-arabinose isomerases and their d-tagatose production is compared. Protein engineering and immobilization of the enzyme for increasing the conversion rate of d-galactose to d-tagatose are also reviewed.


Application l-Arabinose isomerase Biotransformation Properties Tagatose 


  1. Baek DH, Lee Y, Sin HS, Oh DK (2004) A new thermophile strain of Geobacillus thermodenitrificans having l-arabinose isomerase activity for tagatose production. J Microbiol Biotechnol 14:312–316Google Scholar
  2. Bar A, Lina BA, de Groot DM, de Bie B, Appel MJ (1999) Effect of d-tagatose on liver weight and glycogen content of rats. Regul Toxicol Pharmacol 29:S11–S28CrossRefGoogle Scholar
  3. Beadle JR, Saunder JP, Wajada TJ (1991) Process for manufacturing tagatose. US patent 500261Google Scholar
  4. Bertelsen H, Jensen BB, Buemann B (1999) d-Tagatose: a novel low-caloric bulk sweetener with prebiotic properties. World Rev Nutr Diet 85:98–109Google Scholar
  5. Bertelsen H, Andersen H, Tvede M (2001) Fermentation of d-tagatose by human intestinal bacteria and dairy lactic acid bacteria. Microb Ecol Health Dis 13:87–95Google Scholar
  6. Buemann B, Toubro S, Astrup A (1999a) Human gastrointestinal tolerance to d-tagatose. Regul Toxicol Pharmacol 29:S71–S77CrossRefGoogle Scholar
  7. Buemann B, Toubro S, Raben A, Astrup A (1999b) Human tolerance to a single, high dose of d-tagatose. Regul Toxicol Pharmacol 29:S66–S70CrossRefGoogle Scholar
  8. Buemann B, Toubro S, Raben A, Blundell J, Astrup A (2000) The acute effect of d-tagatose on food intake in human subjects. Br J Nutr 84:227–231Google Scholar
  9. Burdock GA, Carabin IG (2004) Generally recognized as safe (GRAS): history and description. Toxicol Lett 150:3–18CrossRefGoogle Scholar
  10. Chang C, Park BC, Lee DS, Suh SW (1999) Crystal structures of thermostable xylose isomerases from Thermus caldophilus and Thermus thermophilus: possible structural determinants of thermostability. J Mol Biol 288:623–634CrossRefGoogle Scholar
  11. Cheetham PSJ, Wootton AN (1993) Bioconversion of d-galactose into d-tagatose. Enzyme Microb Technol 15:105–108CrossRefGoogle Scholar
  12. Cisar JO, Kolenbrander PE, Mclntire FC (1979) Specificity of coaggregation reactions between human oral streptococci and strains of Actinomyces viscosus or Actinomyces naeslundii. Infect Immun 24:742–752Google Scholar
  13. De Muynck C, Beauprez J, Soetaert W, Vandamme EJ (2006) Boric acid as a mobile phase additive for high performance liquid chromatography separation of ribose, arabinose and ribulose. J Chromatogr 1101:115–121CrossRefGoogle Scholar
  14. Donner TW, Wilber JF, Ostrowski D (1999) d-Tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes. Diabetes Obes Metab 1:285–291CrossRefGoogle Scholar
  15. Hicks KB, Parrish FW (1980) A new method for the preparation of lactulose from lactose. Carbohydr Res 82:393–397CrossRefGoogle Scholar
  16. Hicks KB, Symanski EV, Pfeffer PE (1983) Synthesis and high-performance liquid chromatography of maltulose and cellobiulose. Carbohydr Res 112:37–50CrossRefGoogle Scholar
  17. Hong YH, Lee DW, Lee SJ, Choe EA, Kim SB, Lee YH, Cheigh CI, Pyun YR (2007) Production of d-tagatose at high temperatures using immobilized Escherichia coli cells expressing l-arabinose isomerase from Thermotoga neapolitana. Biotechnol Lett 29:569–574CrossRefGoogle Scholar
  18. Ibrahim OO, Spradlin JE (2000) Process for manufacturing d-tagatose. US Patent 6057135Google Scholar
  19. Ishida Y, Kamiya T, Itoh H, Kimura Y, Izumori K (1997) Cloning and characterization of the d-tagatose 3-epimerase gene from Pseudomonas cichorii ST-24. J Ferment Bioeng 83:529–534CrossRefGoogle Scholar
  20. Itoh H, Okaya H, Khan AR, Tajima S, Hayakawa S, Izumori K (1994) Purification and characterization of d-tagatose 3-epimerase from Pseudomonas sp. ST-24. Biosci Biotechnol Biochem 58:2168–2171CrossRefGoogle Scholar
  21. Izumori K, Tsuzaki K (1988) Production of d-tagatose from d-galactitol by Mycobacterium smegmatis. J Ferment Technol 66:225–227CrossRefGoogle Scholar
  22. Izumori K, Ueda Y, Yamanaka K (1978) Pentose metabolism in Mycobacterium smegmatis: comparison of l-arabinose isomerases induced by l-arabinose and d-galactose. J Bacteriol 133:413–414Google Scholar
  23. Izumori K, Miyoshi T, Tokuda S, Yamabe K (1984) Production of d-tagatose from ducitol by Arthrobacter globiformis. Appl Environ Microbiol 46:1055–1057Google Scholar
  24. Jørgensen F, Hansen OC, Stougaard P (2004) Enzymatic conversion of d-galactose to d-tagatose: heterologous expression and characterisation of a thermostable l-arabinose isomerase from Thermoanaerobacter mathranii. Appl Microbiol Biotechnol 64:816–822CrossRefGoogle Scholar
  25. Jung ES, Kim HJ, Oh DK (2005) Tagatose production by immobilized recombinant Escherichia coli cells containing Geobacillus stearothermophilus l-arabinose isomerase mutant in a packed-bed bioreactor. Biotechnol Prog 21:1335–1340CrossRefGoogle Scholar
  26. Kim P (2004) Current studies on biological tagatose production using l-arabinose isomerase: a review and future perspective. Appl Microbiol Biotechnol 65:243–249Google Scholar
  27. Kim HJ, Oh DK (2005) Purification and characterization of an l-arabinose isomerase from an isolated strain of Geobacillus thermodenitrificans producing d-tagatose. J Biotechnol 120:162–173CrossRefGoogle Scholar
  28. Kim P, Yoon SH, Seo MJ, Oh DK, Choi JH (2001a) Improvement of tagatose conversion rate by genetic evolution of thermostable galactose isomerase. Biotechnol Appl Biochem 34:99–102CrossRefGoogle Scholar
  29. Kim P, Yoon SH, Roh HJ, Choi JH (2001b) High production of d-tagatose, a potential sugar substitute, using immobilized l-arabinose isomerase. Biotechnol Prog 17:208–210CrossRefGoogle Scholar
  30. Kim BC, Lee YH, Lee HS, Lee DW, Choe EA, Pyun YR (2002) Cloning, expression and characterization of l-arabinose isomerase from Thermotoga neapolitana: bioconversion of d-galactose to d-tagatose using the enzyme. FEMS Microbiol Lett 212:121–126Google Scholar
  31. Kim HJ, Ryu SA, Kim P, Oh DK (2003a) A feasible enzymatic process for d-tagatose production by an immobilized thermostable l-arabinose isomerase in a packed-bed bioreactor. Biotechnol Prog 19:400–404CrossRefGoogle Scholar
  32. Kim JW, Kim YW, Roh HJ, Kim HY, Cha JH, Park KH, Park CS (2003b) Production of tagatose by a recombinant thermostable l-arabinose isomerase from Thermus sp. IM6501. Biotechnol Lett 25:963–967CrossRefGoogle Scholar
  33. Kim HJ, Hyun EK, Kim YS, Lee YJ, Oh DK (2006a) Characterization of an Agrobacterium tumefaciens d-psicose-3-epimerase that converts d-fructose to d-psicose. Appl Environ Microbiol 72:981–985CrossRefGoogle Scholar
  34. Kim HJ, Kim JH, Oh HJ, Oh DK (2006b) Characterization of a mutated Geobacillus stearothermophilus l-arabinose isomerase that increases the production rate of d-tagatose. J Appl Microbiol 101:213–221CrossRefGoogle Scholar
  35. Köpper S, Freimund S (2003) The composition of keto aldoses in aqueous solution as determined by NMR spectroscopy. Helv Chim Acta 86:827–843CrossRefGoogle Scholar
  36. Lærke HN, Jensen BB (1999) d-Tagatose has low small intestinal digestibility but high large intestinal fermentability in pigs. J Nutr 129:1002–1009Google Scholar
  37. Lærke HN, Jensen BB, Højsgaard S (2000). In vitro fermentation pattern of d-tagatose is affected by adaptation of the microbiota from the gastrointestinal tract of pigs. J Nutr 130:1772–1779Google Scholar
  38. Lee DW, Jang HJ, Choe EA, Kim BC, Lee SJ, Kim SB, Hong YH, Pyun YR (2004) Characterization of a thermostable l-arabinose (d-galactose) isomerase from the hyperthermophilic eubacterium Thermotoga maritima. Appl Environ Microbiol 70:1397–1404CrossRefGoogle Scholar
  39. Lee DW, Choe EA, Kim BC, Eom SH, Hong YH, Lee SJ, Lee HS, Lee DY, Pyun YR (2005a) Distinct metal dependence for catalytic and structural functions in the l-arabinose isomerase from the mesophilic Bacillus halodurans and the thermophilic Geobacillus stearothermophilus. Arch Biochem Biophys 434:333–343CrossRefGoogle Scholar
  40. Lee SJ, Lee DW, Choe EA, Hong YH, Kim SB, Kim BC, Pyun YR (2005b) Characterization of a thermoacidophilic l-arabinose isomerase from Alicyclobacillus acidocaldarius: role of Lys-269 in pH optimum. Appl Environ Microbiol 71:7888–7896CrossRefGoogle Scholar
  41. Levin GV (2000) Increased fertility and improved fetal development. US patent 6225452Google Scholar
  42. Levin GV (2002) Tagatose, the new GRAS sweetener and health product. J Med Food 5:23–36CrossRefGoogle Scholar
  43. Levin GV, Zehner LR, Saunders JP, Beadle JR (1995) Sugar substitutes: their energy values, bulk characteristics, and potential health benefits. Am J Clin Nutr 62:S1161–S1168Google Scholar
  44. Livesey G, Brown JC (1996) d-Tagatose is a bulk sweetener with zero energy determined in rats. J Nutr 126:1601–1609Google Scholar
  45. Manjasetty BA, Chance MR (2006) Crystal Structure of Escherichia coli l-arabinose isomerase (ECAI), the putative target of biological tagatose production. J Mol Biol 360:297–309CrossRefGoogle Scholar
  46. Manzoni M, Rollini M (2001) Bioconversion of d-galactitol to tagatose by acetic acid bacteria. Process Biochem 36:971–977CrossRefGoogle Scholar
  47. Mendoza MR, Olano A, Villamiel M (2005) Chemical indicators of heat treatment in fortified and special milks. J Agric Food Chem 53:2995–2999CrossRefGoogle Scholar
  48. Moore MC (2006) Drug evaluation: tagatose in the treatment of type 2 diabetes and obesity. Curr Opin Investig Drugs 7:924–935Google Scholar
  49. Muniruzzanman S, Tokunaga H, Izumori K (1994) Isolation of Enterobacter agglomerans strain 221e from soil, a potent d-tagatose producer from galactitol. J Ferment Bioeng 78:145–148CrossRefGoogle Scholar
  50. Nakamatu T, Yamanaka K (1969) Crystallization and properties of l-arabinose isomerase from Lactobacillus gayonii. Biochim Biophys Acta 178:156–165Google Scholar
  51. Oh DK, Roh HJ, Kim SY, Noh BS (1998) Optimization of culture conditions for d-tagatose production from d-galactose by Enterobacter agglomerans. Kor J Appl Microbiol Biotechnol 26:250–256Google Scholar
  52. Oh DK, Kim HJ, Ryu SA, Kim P (2001) Development of an immobilization method of l-arabinose isomerase for industrial production of tagatose. Biotechnol Lett 23:1859–1862CrossRefGoogle Scholar
  53. Oh DK, Kim HJ, Oh HJ, Cheon J, Kim P (2006a) Modification of optimal pH in l-arabinose isomerase from Geobacillus stearothermophilus for d-galactose isomerization. J Mol Catal B Enzym 43:108–112CrossRefGoogle Scholar
  54. Oh HJ, Kim HJ, Oh DK (2006b) Increase in d-tagatose production rate by site-directed mutagenesis of l-arabinose isomerase from Geobacillus thermodenitrificans. Biotechnol Lett 28:145–149CrossRefGoogle Scholar
  55. Paterna JC, Boess F, Stäubli A, Boelsterli UA (1998) Antioxidant and cytoprotective properties of d-tagatose in cultured murine hepatocytes. Toxicol Appl Pharm 148:117–125CrossRefGoogle Scholar
  56. Patrick JW, Lee N (1968) Purification and properties of an l-arabinose isomerase from Escherichia coli. J Biol Chem 243:4312–4318Google Scholar
  57. Rhimi M, Messaoud EB, Borgi MA, Khadra KB, Bejar S (2007a) Co-expression of l-arabinose isomerase and d-glucose isomerase in E. coli and development of an efficient process producing simultaneously d-tagatose and d-fructose. Enzyme Microb Technol 40:1531–1537CrossRefGoogle Scholar
  58. Rhimi M, Juy M, Aghajari N, Haser R, Bejar S (2007b) Probing the essential catalytic residues and the substrate affinity in the thermoactive Bacillus stearothermophilus US100 l-arabinose isomerase by site-directed mutagenesis. J Bacteriol 189:3556–3563CrossRefGoogle Scholar
  59. Richards EL, Chandrasekhara MR (1960) Chemical changes in dried skim milk during storage. J Dairy Res 27:59–66CrossRefGoogle Scholar
  60. Roh HJ, Kim P, Park YC, Choi JH (2000a) Bioconversion of d-galactose into d-tagatose by expression of l-arabinose isomerase. Biotechnol Appl Biochem 31:1–4CrossRefGoogle Scholar
  61. Roh HJ, Yoon SH, Kim P (2000b) Preparation of l-arabinose isomerase originated from Escherichia coli as a biocatalyst for d-tagatose production. Biotechnol Lett 22:197–199CrossRefGoogle Scholar
  62. Rollini M, Manzoni M (2005) Bioconversion of d-galactitol to tagatose and dehydrogenase activity induction in Gluconobacter oxydans. Process Biochem 40:437–444CrossRefGoogle Scholar
  63. Rosenplenter K, Mende K (2004) Use of d-tagatose for improving aroma and flavor in foods and beverages. WO patent 2004/073419Google Scholar
  64. Ryu SA, Kim CS, Kim HJ, Baek DH, Oh DK (2003) Continuous d-tagatose production by immobilized thermostable l-arabinose isomerase in a packed-bed bioreactor. Biotechnol Prog 19:1643–1647CrossRefGoogle Scholar
  65. Seri K, Sanai K, Negishi S, Akino T (1993) Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food. European Patent 560284Google Scholar
  66. Shimonishi T, Okumura Y, Izumori K (1994) Production of d-tagatose from galactitol by Klebsiella pneumoniae strain 40b. J Ferment Bioeng 78:145–148CrossRefGoogle Scholar
  67. Smith KW, Johnson SL (1976) Borate inhibition of yeast alcohol dehydrogenase. Biochemistry 15:560–565CrossRefGoogle Scholar
  68. Takeshita K, Suga A, Takada G, Izumori K (2000) Mass production of d-psicose from d-fructose by a continuous bioreactor system using immobilized d-tagatose 3-epimerase. J Biosci Bioeng 90:453–455Google Scholar
  69. Troyono E, Martinez-Castro I, Olano A (1992) Kinetics of galactose and tagatose formation during heat-treatment of milk. Food Chem 45:41–43CrossRefGoogle Scholar
  70. Wong D (2000) Sweetener determined safe in drugs, mouthwashes, and toothpastes. Dent Today 19:34–35Google Scholar
  71. Yamanaka K, Wood WA (1966) l-Arabinose isomerase. Methods Enzymol 9:596–602CrossRefGoogle Scholar
  72. Yoon SH, Kim P, Oh DK (2003) Properties of l-arabinose isomerase from Escherichia coli as biocatalysis for tagatose production. World J Microbiol Biotechnol 19:47–51CrossRefGoogle Scholar
  73. Yoshida H, Yamada M, Nishitani T, Takada G, Izumori K, Kamitori S. (2007) Purification, crystallization and preliminary X-ray diffraction studies of d-tagatose 3-epimerase from Pseudomonas cichorii. Acta Crystallog Sect F Struct Biol Cryst Commun 63:123–125CrossRefGoogle Scholar
  74. Yoshihara K, Shinohara Y, Hirotsu T, Izumori K (2006) Bioconversion of d-psicose to d-tagatose and d-talitol by Mucoraceae Fungi. J Biosci Bioeng 100:219–222CrossRefGoogle Scholar
  75. Zehner LR, Lee R (1988) d-Tagatose as a low-calorie carbohydrate sugar and bulking agent. European patent 257626Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Bioscience and BiotechnologyKonkuk UniversitySeoulSouth Korea

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