Applied Microbiology and Biotechnology

, Volume 83, Issue 2, pp 209–216

Towards tailor-made oligosaccharides—chemo-enzymatic approaches by enzyme and substrate engineering

Mini-Review

Abstract

Carbohydrate structures have been identified in eukaryotic and prokaryotic cells as glycoconjugates with communication skills. Their recently discussed role in various diseases has attracted high attention in the development of simple and convenient methods for oligosaccharide synthesis. In this review, recent approaches combining nature’s power for the design of tailor made biocatalysts by enzyme engineering and substrate engineering will be presented. These strategies lead to highly efficient and selective glycosylation reactions. The introduced concept shall be a first step in the direction to a glycosylation toolbox which paves the way for the tailor-made synthesis of designed carbohydrate structures.

Keywords

Tailor-made oligosaccharides Enzyme engineering Substrate engineering Glucosyltransferase Fructosyltransferase 

References

  1. Avigad G, Feingold DS, Hestrin S (1957) Enzymatic synthesis and reactions of a sucrose isomer α-D-galactopyranosyl-β-D-fructofuranoside. J Biol Chem 224:295–307Google Scholar
  2. Beine R, Moraru R, Nimtz M, Na'amnieh S, Pawlowski A, Buchholz K, Seibel J (2008) Synthesis of novel fructooligosaccharides by substrate and enzyme engineering. J Biotechnol 138:33–41CrossRefGoogle Scholar
  3. Biedendieck R, Beine R, Gamer M, Jordan E, Buchholz K, Seibel J, Dijkhuizen L, Malten M, Jahn D (2007) Export, purification, and activities of affinity tagged Lactobacillus reuteri levansucrase produced by Bacillus megaterium. Appl Microbiol Biotechnol 74:1062–1073CrossRefGoogle Scholar
  4. Blanchard S, Armand S, Couthino P, Patkar S, Vind J, Samain E, Driguez H, Cottaz S (2007) Unexpected regioselectivity of Humicola insolens Cel7B glycosynthase mutants. Carbohydr Res 342:710–716CrossRefGoogle Scholar
  5. Bloom JD, Meyer MM, Meinhold P, Otey CR, MacMillan D, Arnold FH (2005) Evolving strategies for enzyme engineering. Curr Opin Struct Biol 15:447–452CrossRefGoogle Scholar
  6. Buchholz K, Seibel J (2003) Isomaltooligosaccharides. In: Eggleston G, Cote GL (eds) Oligosaccharides in food and agriculture. Oxford University Press, Washington, DC, pp 63–75Google Scholar
  7. Buchholz K, Noll-Borchers M, Schwengers D (1998) Production of leucrose by dextransucrase. Starch 50:162–164CrossRefGoogle Scholar
  8. Cantarel B, Coutinho P, Rancurel C, Bernard T, Lombard V, Henrissat B (2009) The carbohydrate-active enzymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res 37:233–238CrossRefGoogle Scholar
  9. Chambert R, Petit-Glatron MF (1991) Polymerase and hydrolase activities of Bacillus subtilis levansucrase can be separately modulated by site-directed mutagenesis. Biochem J 279:35–41Google Scholar
  10. Cheetham PSJ, Hacking AJ, Vlitos M (1989) Synthesis of novel disaccharides by a newly isolated fructosyltransferase from Bacillus subtilis Enz. Microb Technol 11:212–219CrossRefGoogle Scholar
  11. DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific LLC, San Carlos, CAGoogle Scholar
  12. Demuth K, Jördening HJ, Buchholz K (2002) Oligosaccharide synthesis by dextransucrase: new unconventional acceptors. Carbohydr Res 337:1811–1820CrossRefGoogle Scholar
  13. Devulapalle KS, Goodman SD, Gao Q, Hemsley A, Mooser G (1997) Knowledge-based model of a glucosyltransferase from the oral bacterial group of mutans streptococci. Protein Sci 6:2489–2493CrossRefGoogle Scholar
  14. Dols M, Remaud-Simeon M, Willemot RM, Vignon M, Monsan P (1998) Characterization of the different dextransucrase activities excreted in glucose, fructose, or sucrose medium by Leuconostoc mesenteroides NRRL B-1299. Appl Environ Microbiol 64:1298–1302Google Scholar
  15. Hellmuth H, Hillringhaus L, Höbbel S, Kralj S, Dijkhuizen L, Seibel J (2007) Highly efficient chemoenzymatic synthesis of novel branched thiooligosaccharides by substrate direction with glucansucrases. Chembiochem 8:273–276CrossRefGoogle Scholar
  16. Hellmuth H, Wittrock S, Kralj S, Dijkhuizen L, Hofer B, Seibel J (2008) Engineering the glucansucrase GTFR enzyme reaction and glycosidic bond specificity: toward tailor-made polymer and oligosaccharide products. Biochemistry 47:6678–6684CrossRefGoogle Scholar
  17. Homann A, Biedendieck R, Gotze S, Jahn D, Seibel J (2007) Insights into polymer versus oligosaccharide synthesis: mutagenesis and mechanistic studies of a novel levansucrase from Bacillus megaterium. Biochem J 407:189–198CrossRefGoogle Scholar
  18. Kato C, Nakano Y, Lis M, Kuramitsu HK (1992) Molecular genetic analysis of the catalytic site of Streptococcus mutans glucosyltransferases. Biochem Biophys Res Commun 189:1184–1188CrossRefGoogle Scholar
  19. Kralj S, van Geel-Schutten GH, van der Maarel MJ, Dijkhuizen L (2004) Biochemical and molecular characterization of Lactobacillus reuteri 121 reuteransucrase. Microbiology 150:2099–2112CrossRefGoogle Scholar
  20. Kralj S, van Geel-Schutten IG, Faber EJ, van der Maarel MJ, Dijkhuizen L (2005) Rational transformation of Lactobacillus reuteri 121 reuteransucrase into a dextransucrase. Biochemistry 44:9206–9216CrossRefGoogle Scholar
  21. Kralj S, Eeuwema W, Eckhardt TH, Dijkhuizen L (2006) Role of asparagine 1134 in glucosidic bond and transglycosylation specificity of reuteransucrase from Lactobacillus reuteri 121. FEBS J 273:3735CrossRefGoogle Scholar
  22. Lairson LL, Watts AG, Wakarchuk WW, Withers SG (2006) Using substrate engineering to harness enzymatic promiscuity and expand biological catalysis. Nat Chem Biol 2:724–728CrossRefGoogle Scholar
  23. Lina BA, Jonker D, Kozianowski G (2002) Isomaltulose (Palatinose): a review of biological and toxicological studies. Food Chem Toxicol 40:1375–1381CrossRefGoogle Scholar
  24. MacGregor EA, Jespersen HM, Svensson B (1996) A circularly permuted alpha-amylase-type alpha/beta-barrel structure in glucan-synthesizing glucosyltransferases. FEBS Lett 378:263–266CrossRefGoogle Scholar
  25. Meng G, Fütterer K (2008) Donor substrate recognition in the raffinose-bound E342A mutant of fructosyltransferase Bacillus subtilis levansucrase. BMC Struct Biol 8:16CrossRefGoogle Scholar
  26. Meng G, Fütterer K (2003) Structural framework of fructosyl transfer in Bacillus subtilis levansucrase. Nat Struct Biol 10:935–941CrossRefGoogle Scholar
  27. Mizubuchi H, Yajima T, Aoi N, Tomita T, Yoshikai Y (2005) Isomalto-oligosaccharides polarize Th1-like responses in intestinal and systemic immunity in mice. J Nutr 135:2857–2861Google Scholar
  28. Monchois V, Remaud-Simeon M, Russell RR, Monsan P, Willemot RM (1997) Characterization of Leuconostoc mesenteroides NRRL B-512F dextransucrase (DSRS) and identification of amino-acid residues playing a key role in enzyme activity. Appl Microbiol Biotechnol 48:465–472CrossRefGoogle Scholar
  29. Monchois V, Willemot RM, Monsan P (1999) Glucansucrases: mechanism of action and structure-function relationships. FEMS Microbiol Rev 23:131–151CrossRefGoogle Scholar
  30. Mooser G, Hefta SA, Paxton RJ, Shively JE, Lee TD (1991) Isolation and sequence of an active-site peptide containing a catalytic aspartic acid from two Streptococcus sobrinus alpha-glucosyltransferases. J Biol Chem 266:8916–8922Google Scholar
  31. Nakakuki T (2002) Present status and future of functional oligosaccharide development in Japan. Pure Appl Chem 74:1245–1251CrossRefGoogle Scholar
  32. Pachamuthu K, Schmidt RR (2006) Synthetic routes to thiooligosaccharides and thioglycopeptides. Chem Rev 106:160–187CrossRefGoogle Scholar
  33. Pietsch M, Walter W, Buchholz K (1994) Regioselective synthesis of new sucrose derivatives via 3-ketosucrose. Carbohydr Res 254:183–194CrossRefGoogle Scholar
  34. Remaud-Simeon M, Willemot R, Sarcabal P, Potocki de Montalk G, Monsan P (2000) Glucansucrases: molecular engineering and oligosaccharide synthesis. J Mol Catal B Enzymatic 10:117–128CrossRefGoogle Scholar
  35. Seibel J, Moraru R, Götze S (2005) Biocatalytic and chemical investigations in the synthesis of sucrose analogues. Tetrahedron 61:7081–7086CrossRefGoogle Scholar
  36. Seibel J, Beine R, Moraru R, Behringer C, Buchholz K (2006a) A new pathway for the synthesis of oligosaccharides by the use of non-Leloir glycosyltransferases. Biocat Biotrans 24:157–165CrossRefGoogle Scholar
  37. Seibel J, Hellmuth H, Hofer B, Kicinska AM, Schmalbruch B (2006b) Identification of new acceptor specificities of glycosyltransferase R with the aid of substrate microarrays. Chembiochem 7:310–320CrossRefGoogle Scholar
  38. Seibel J, Moraru R, Götze S, Buchholz K, Na'amnieh S, Pawlowski A, Hecht HJ (2006c) Synthesis of sucrose analogues and the mechanism of action of Bacillus subtilis fructosyltransferase (levansucrase). Carbohydr Res 341:2335–2349CrossRefGoogle Scholar
  39. Shaikh FA, Withers SG (2008) Teaching old enzymes new tricks: engineering and evolution of glycosidases and glycosyl transferases for improved glycoside synthesis. Biochem Cell Biol 86:169–177CrossRefGoogle Scholar
  40. Shao Z, Arnold FH (1996) Engineering new functions and altering existing functions. Curr Opin Struct Biol 6:513–518CrossRefGoogle Scholar
  41. Shimamura A, Nakano YJ, Mukasa H, Kuramitsu HK (1994) Identification of amino acid residues in Streptococcus mutans glucosyltransferases influencing the structure of the glucan product. J Bacteriol 176:4845–4850Google Scholar
  42. Stoppok E, Matalla K, Buchholz K (1992) Microbial modification of sugars as building blocks for chemicals. Appl Microb Biotechnol 36:604–610CrossRefGoogle Scholar
  43. Swistowska AM, Gronert S, Wittrock S, Collisi W, Hecht HJ, Hofer B (2007) Identification of structural determinants for substrate binding and turnover by glucosyltransferase R supports the permutation hypothesis. FEBS Lett 581:4036–4042CrossRefGoogle Scholar
  44. Timme V, Buczys R, Buchholz K (1998) Kinetic investigations on the hydrogenation of 3-ketosucrose. Starch/Stärke 50:29–32CrossRefGoogle Scholar
  45. van Hijum SA, Kralj S, Ozimek LK, Dijkhuizen L, van Geel-Schutten IG (2006) Structure-function relationships of glucansucrase and fructansucrase enzymes from lactic acid bacteria. Microbiol Mol Biol Rev 70:157–176CrossRefGoogle Scholar
  46. Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97CrossRefGoogle Scholar
  47. Witczak ZJ, Kaplon P, Dey PM (2003) Thio-sugars VII. Effect of 3-deoxy-4-S-(β-D-gluco- and β-D-galactopyranosyl)-4-thiodisaccharides and their sulfoxides and sulfones on the viability and growth of selected murine and human tumor cell lines. Carbohydr Res 338:11–18CrossRefGoogle Scholar
  48. Wong CH (2005) Protein glycosylation: new challenges and opportunities. J Org Chem 70:4219–4225CrossRefGoogle Scholar
  49. Yun JW (1996) Fructooligosaccharides—occurrence, preparation and application. Enzyme Microb Technol 19:107–117CrossRefGoogle Scholar
  50. Zuccaro A, Götze S, Kneip S, Dersch P, Seibel J (2008) Tailor-made fructooligosaccharides by a combination of substrate and genetic engineering. Chembiochem 9:143–149CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Institute of Organic Chemistry, University of WürzburgWürzburgGermany

Personalised recommendations