Skip to main content
Log in

Tagatose: properties, applications, and biotechnological processes

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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 14:312–316

    CAS  Google Scholar 

  • 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–S28

    CAS  PubMed  Google Scholar 

  • Beadle JR, Saunder JP, Wajada TJ (1991) Process for manufacturing tagatose. US patent 500261

  • Bertelsen H, Jensen BB, Buemann B (1999) d-Tagatose: a novel low-caloric bulk sweetener with prebiotic properties. World Rev Nutr Diet 85:98–109

    CAS  PubMed  Google Scholar 

  • Bertelsen H, Andersen H, Tvede M (2001) Fermentation of d-tagatose by human intestinal bacteria and dairy lactic acid bacteria. Microb Ecol Health Dis 13:87–95

    CAS  Google Scholar 

  • Buemann B, Toubro S, Astrup A (1999a) Human gastrointestinal tolerance to d-tagatose. Regul Toxicol Pharmacol 29:S71–S77

    CAS  PubMed  Google Scholar 

  • Buemann B, Toubro S, Raben A, Astrup A (1999b) Human tolerance to a single, high dose of d-tagatose. Regul Toxicol Pharmacol 29:S66–S70

    CAS  PubMed  Google Scholar 

  • 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 84:227–231

    CAS  PubMed  Google Scholar 

  • Burdock GA, Carabin IG (2004) Generally recognized as safe (GRAS): history and description. Toxicol Lett 150:3–18

    CAS  PubMed  Google Scholar 

  • 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 288:623–634

    CAS  PubMed  Google Scholar 

  • Cheetham PSJ, Wootton AN (1993) Bioconversion of d-galactose into d-tagatose. Enzyme Microb Technol 15:105–108

    CAS  Google Scholar 

  • 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 24:742–752

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 1101:115–121

    Google Scholar 

  • 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 1:285–291

    CAS  PubMed  Google Scholar 

  • Hicks KB, Parrish FW (1980) A new method for the preparation of lactulose from lactose. Carbohydr Res 82:393–397

    CAS  Google Scholar 

  • Hicks KB, Symanski EV, Pfeffer PE (1983) Synthesis and high-performance liquid chromatography of maltulose and cellobiulose. Carbohydr Res 112:37–50

    CAS  Google Scholar 

  • 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 29:569–574

    CAS  PubMed  Google Scholar 

  • Ibrahim OO, Spradlin JE (2000) Process for manufacturing d-tagatose. US Patent 6057135

  • 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 83:529–534

    CAS  Google Scholar 

  • 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 58:2168–2171

    CAS  Google Scholar 

  • Izumori K, Tsuzaki K (1988) Production of d-tagatose from d-galactitol by Mycobacterium smegmatis. J Ferment Technol 66:225–227

    CAS  Google Scholar 

  • 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 133:413–414

    CAS  PubMed  PubMed Central  Google Scholar 

  • Izumori K, Miyoshi T, Tokuda S, Yamabe K (1984) Production of d-tagatose from ducitol by Arthrobacter globiformis. Appl Environ Microbiol 46:1055–1057

    Google Scholar 

  • 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 64:816–822

    PubMed  Google Scholar 

  • Jung ES, Kim HJ, Oh DK (2005) Tagatose production by immobilized recombinant Escherichia coli cells containing Geobacillus stearothermophilusl-arabinose isomerase mutant in a packed-bed bioreactor. Biotechnol Prog 21:1335–1340

    CAS  PubMed  Google Scholar 

  • Kim P (2004) Current studies on biological tagatose production using l-arabinose isomerase: a review and future perspective. Appl Microbiol Biotechnol 65:243–249

    CAS  PubMed  Google Scholar 

  • 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 120:162–173

    CAS  PubMed  Google Scholar 

  • 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 34:99–102

    CAS  PubMed  Google Scholar 

  • 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 17:208–210

    CAS  PubMed  Google Scholar 

  • 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 212:121–126

    CAS  PubMed  Google Scholar 

  • 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 19:400–404

    CAS  PubMed  Google Scholar 

  • 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 25:963–967

    CAS  PubMed  Google Scholar 

  • Kim HJ, Hyun EK, Kim YS, Lee YJ, Oh DK (2006a) Characterization of an Agrobacterium tumefaciensd-psicose-3-epimerase that converts d-fructose to d-psicose. Appl Environ Microbiol 72:981–985

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim HJ, Kim JH, Oh HJ, Oh DK (2006b) Characterization of a mutated Geobacillus stearothermophilusl-arabinose isomerase that increases the production rate of d-tagatose. J Appl Microbiol 101:213–221

    CAS  PubMed  Google Scholar 

  • Köpper S, Freimund S (2003) The composition of keto aldoses in aqueous solution as determined by NMR spectroscopy. Helv Chim Acta 86:827–843

    Google Scholar 

  • Lærke HN, Jensen BB (1999) d-Tagatose has low small intestinal digestibility but high large intestinal fermentability in pigs. J Nutr 129:1002–1009

    PubMed  Google Scholar 

  • 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 130:1772–1779

    PubMed  Google Scholar 

  • 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 70:1397–1404

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 434:333–343

    CAS  PubMed  Google Scholar 

  • 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 71:7888–7896

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levin GV (2000) Increased fertility and improved fetal development. US patent 6225452

  • Levin GV (2002) Tagatose, the new GRAS sweetener and health product. J Med Food 5:23–36

    CAS  PubMed  Google Scholar 

  • 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–S1168

    Google Scholar 

  • Livesey G, Brown JC (1996) d-Tagatose is a bulk sweetener with zero energy determined in rats. J Nutr 126:1601–1609

    CAS  PubMed  Google Scholar 

  • Manjasetty BA, Chance MR (2006) Crystal Structure of Escherichia colil-arabinose isomerase (ECAI), the putative target of biological tagatose production. J Mol Biol 360:297–309

    CAS  PubMed  Google Scholar 

  • Manzoni M, Rollini M (2001) Bioconversion of d-galactitol to tagatose by acetic acid bacteria. Process Biochem 36:971–977

    CAS  Google Scholar 

  • Mendoza MR, Olano A, Villamiel M (2005) Chemical indicators of heat treatment in fortified and special milks. J Agric Food Chem 53:2995–2999

    CAS  PubMed  Google Scholar 

  • Moore MC (2006) Drug evaluation: tagatose in the treatment of type 2 diabetes and obesity. Curr Opin Investig Drugs 7:924–935

    CAS  PubMed  Google Scholar 

  • 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 78:145–148

    Google Scholar 

  • Nakamatu T, Yamanaka K (1969) Crystallization and properties of l-arabinose isomerase from Lactobacillus gayonii. Biochim Biophys Acta 178:156–165

    CAS  PubMed  Google Scholar 

  • 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 26:250–256

    CAS  Google Scholar 

  • 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 23:1859–1862

    CAS  Google Scholar 

  • 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 43:108–112

    CAS  Google Scholar 

  • 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 28:145–149

    CAS  PubMed  Google Scholar 

  • Paterna JC, Boess F, Stäubli A, Boelsterli UA (1998) Antioxidant and cytoprotective properties of d-tagatose in cultured murine hepatocytes. Toxicol Appl Pharm 148:117–125

    CAS  Google Scholar 

  • Patrick JW, Lee N (1968) Purification and properties of an l-arabinose isomerase from Escherichia coli. J Biol Chem 243:4312–4318

    CAS  PubMed  Google Scholar 

  • 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 40:1531–1537

    CAS  Google Scholar 

  • 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 189:3556–3563

    CAS  PubMed  PubMed Central  Google Scholar 

  • Richards EL, Chandrasekhara MR (1960) Chemical changes in dried skim milk during storage. J Dairy Res 27:59–66

    CAS  Google Scholar 

  • 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 31:1–4

    CAS  PubMed  Google Scholar 

  • 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 22:197–199

    CAS  Google Scholar 

  • Rollini M, Manzoni M (2005) Bioconversion of d-galactitol to tagatose and dehydrogenase activity induction in Gluconobacter oxydans. Process Biochem 40:437–444

    CAS  Google Scholar 

  • Rosenplenter K, Mende K (2004) Use of d-tagatose for improving aroma and flavor in foods and beverages. WO patent 2004/073419

  • 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 19:1643–1647

    CAS  PubMed  Google Scholar 

  • Seri K, Sanai K, Negishi S, Akino T (1993) Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food. European Patent 560284

  • Shimonishi T, Okumura Y, Izumori K (1994) Production of d-tagatose from galactitol by Klebsiella pneumoniae strain 40b. J Ferment Bioeng 78:145–148

    Google Scholar 

  • Smith KW, Johnson SL (1976) Borate inhibition of yeast alcohol dehydrogenase. Biochemistry 15:560–565

    CAS  PubMed  Google Scholar 

  • 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 90:453–455

    CAS  PubMed  Google Scholar 

  • Troyono E, Martinez-Castro I, Olano A (1992) Kinetics of galactose and tagatose formation during heat-treatment of milk. Food Chem 45:41–43

    Google Scholar 

  • Wong D (2000) Sweetener determined safe in drugs, mouthwashes, and toothpastes. Dent Today 19:34–35

    Google Scholar 

  • Yamanaka K, Wood WA (1966) l-Arabinose isomerase. Methods Enzymol 9:596–602

    CAS  Google Scholar 

  • Yoon SH, Kim P, Oh DK (2003) Properties of l-arabinose isomerase from Escherichia coli as biocatalysis for tagatose production. World J Microbiol Biotechnol 19:47–51

    CAS  Google Scholar 

  • 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 63:123–125

    CAS  Google Scholar 

  • 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 100:219–222

    Google Scholar 

  • Zehner LR, Lee R (1988) d-Tagatose as a low-calorie carbohydrate sugar and bulking agent. European patent 257626

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deok-Kun Oh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, DK. Tagatose: properties, applications, and biotechnological processes. Appl Microbiol Biotechnol 76, 1–8 (2007). https://doi.org/10.1007/s00253-007-0981-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-007-0981-1

Keywords

Navigation