Microbial aldolases as C–C bonding enzymes—unknown treasures and new developments



Aldolases are a specific group of lyases that catalyze the reversible stereoselective addition of a donor compound (nucleophile) onto an acceptor compound (electrophile). Whereas most aldolases are specific for their donor compound in the aldolization reaction, they often tolerate a wide range of aldehydes as acceptor compounds. C–C bonding by aldolases creates stereocenters in the resulting aldol products. This makes aldolases interesting tools for asymmetric syntheses of rare sugars or sugar-derived compounds as iminocyclitols, statins, epothilones, and sialic acids. Besides the well-known fructose 1,6-bisphosphate aldolase, other aldolases of microbial origin have attracted the interest of synthetic bio-organic chemists in recent years. These are either other dihydroxyacetone phosphate aldolases or aldolases depending on pyruvate/phosphoenolpyruvate, glycine, or acetaldehyde as donor substrate. Recently, an aldolase that accepts dihydroxyacetone or hydroxyacetone as a donor was described. A further enlargement of the arsenal of available chemoenzymatic tools can be achieved through screening for novel aldolase activities and directed evolution of existing aldolases to alter their substrate- or stereospecifities. We give an update of work on aldolases, with an emphasis on microbial aldolases.


  1. Allen ST, Heintzelman GR, Toone EJ (1992) Pyruvate aldolases as reagents for stereospecific aldol condensations. J Org Chem 57:426–427CrossRefGoogle Scholar
  2. Azéma L, Bringaud F, Blonski C, Périé J (2000) Chemical and enzymatic synthesis of fructose analogues as probes for import studies by hexose transporter in parasites. Bioorg Med Chem 8:717–722CrossRefPubMedGoogle Scholar
  3. Barbas CF III, Wang Y-F, Wong C-H (1990) Deoxyribose-5-phosphate aldolase as a synthetic catalyst. J Am Chem Soc 112:2013–2014CrossRefGoogle Scholar
  4. Bednarski MD, Simon ES, Bischofberger N, Fessner W-D, Kim M-J, Lees W, Saito T, Waldmann H, Whitesides GM (1989) Rabbit muscle aldolase as a catalyst in organic synthesis. J Am Chem Soc 111:627–635CrossRefGoogle Scholar
  5. Blayer S, Woodley JM, Dawson MJ, Lilly MD (1999) Alkaline biocatalysis for the direct synthesis of N-acetyl-D-neuraminic Acid (Neu5Ac) from N-acetyl-D-glucosamine (GlcNAc). Biotechnol Bioeng 66:131–136CrossRefPubMedGoogle Scholar
  6. Breuer M, Hauer B (2003) Carbon–carbon coupling in biotransformation. Curr Opin Biotechnol 14:570–576CrossRefPubMedGoogle Scholar
  7. Buchanan CL, Connaris H, Danson MJ, Reeve CD, Hough DW (1999) An extremely thermostable aldolase from Sulfolobus solfataricus with specificity for non-phosphorylated substrates. Biochem J 343:563–570CrossRefPubMedGoogle Scholar
  8. Chenevert R, Dasser M (2000) Chemoenzymatic synthesis of the microbial elicitor (−)-syringolide via a fructose 1,6-diphosphate aldolase-catalyzed condensation reaction. J Org Chem 65:4529–4531CrossRefPubMedGoogle Scholar
  9. Cho MC, Kang D-O, Yoon BD, Lee K (2000) Toluene degradation pathway from Pseudomonas putida F1: substrate specificity and gene induction by 1-substituted benzenes. J Ind Microbiol Biotechnol 25:163–170CrossRefGoogle Scholar
  10. Crestia D, Guérard C, Bolte J, Demuynck C (2001) Rabbit muscle aldolase (RAMA) as a catalyst in a new approach for the synthesis of 3-deoxy-D-manno-2-octulosonic acid and analogues. J Mol Catal B Enzym 11:207–212CrossRefGoogle Scholar
  11. Crestia D, Demuynck C, Bolte J (2004) Transketolase and fructose-1,6-bis-phosphate aldolase, complementary tools for access to new ulosonic acid analogues. Tetrahedron 60:2417–2425CrossRefGoogle Scholar
  12. David S (1999) Enzymatic synthesis of a branched-chain hexulose: 5-deoxy-5-C-hydroxymethyl-β-L-xylo-hex-2-ulopyranose. Eur J Org Chem 1415–1420Google Scholar
  13. DeSantis G, Liu J, Clark DP, Heine A, Wilson IA, Wong CH (2003) Structure-based mutagenesis approaches toward expanding the substrate specificity of D-2-deoxyribose-5-phosphate aldolase. Bioorg Med Chem 11:43–52CrossRefPubMedGoogle Scholar
  14. Dinkelbach M, Hodenius M, Steigel A, Kula MR (2001) Fructose-1,6-bisphosphate aldolases from Staphylococcus carnosus: stereoselective enzymatic synthesis of ketose-1-phosphates and successive reaction to 1,3-dioxanes. Biocatal Biotransform 19:51–68Google Scholar
  15. Durrwachter JR, Drueckhammer DG, Nozaki K, Sweers HM, Wong CH (1986) Enzymatic aldol condensation/isomerization as a route to unusual sugar derivatives. J Am Chem Soc 108:7812–7818CrossRefGoogle Scholar
  16. Eaton RW (2000) trans-o-hydroxybenzylidenepyruvate hydratase–aldolase as a biocatalyst. Appl Environ Microbiol 66:2668–2672CrossRefPubMedGoogle Scholar
  17. Espelt L, Parella T, Bujons J, Solans C, Joglar J, Delgado A, Clapés P (2003) Stereoselective aldol additions catalyzed by dihydroxyacetone phosphate-dependent aldolases in emulsion systems: preparation and structural characterization of linear and cyclic iminopolyols from aminoaldehydes. Chem Eur J 9:4887–4899CrossRefGoogle Scholar
  18. Espelt L, Bujons J, Parella T, Calveras J, Joglar J, Delgado A, Clapés P (2005) Aldol additions of dihydroxyacetone phosphate to N-Cbz-amino aldehydes catalyzed by L-fuculose-1-phosphate aldolase in emulsion systems: inversion of stereoselectivity as a function of the acceptor aldehydes. Chem Eur J 11:1392–1401CrossRefGoogle Scholar
  19. Fessner WD (1998) Enzyme mediated C–C bond formation. Curr Opin Chem Biol 2:85–97CrossRefPubMedGoogle Scholar
  20. Fessner WD, Helaine V (2001) Biocatalytic synthesis of hydroxylated natural products using aldolases and related enzymes. Curr Opin Biotechnol 12:574–586CrossRefPubMedGoogle Scholar
  21. Fessner WD, Walter C (1992) “Artificial metabolisms” for the asymmetric one-pot synthesis of branched-chain saccharides. Angew Chem Int Ed Engl 31:614–616CrossRefGoogle Scholar
  22. Fessner WD, Walter C (1997) Enzymatic C–C bond formation in asymmetric synthesis. Bioorganic Chem Top Curr Chem 184:97–194Google Scholar
  23. Fessner WD, Sinerius G, Schneider A, Dreyer M, Schulz GE, Badia J, Aguilar J (1991) Enzymes in organic synthesis. 1. Diastereoselective enzymatic aldol additions—L-rhamnulose and L-fuculose 1-phosphate aldolases from Escherichia coli. Angew Chem Int Ed Eng 30:555–558CrossRefGoogle Scholar
  24. Fessner WD, Goβe C, Jaeschke G, Eyrisch O (2000) Enzymes in organic synthesis, short enzymatic synthesis of L-fucose analogs. Eur J Org Chem 125–132Google Scholar
  25. Fong S, Machajewski TD, Mak CC, Wong CH (2000) Directed evolution of D-2-keto-3-deoxy-6-phosphogluconate aldolase to new variants for the efficient synthesis of D- and L-sugars. Chem Biol 7:873–883CrossRefPubMedGoogle Scholar
  26. Franke D, Machajewski T, Hsu CC, Wong C-H (2003) One-pot synthesis of L-fructose using coupled multienzyme systems based on rhamnulose-1-phosphate aldolase. J Org Chem 68:6828–6831CrossRefPubMedGoogle Scholar
  27. Franke D, Hsu C-C, Wong C-H (2004) Directed evolution of aldolases. Methods Enzymol 388:224–238PubMedCrossRefGoogle Scholar
  28. Garcia-Junceda E, Shen G-J, Sugai T, Wong C-H (1995) A new strategy for the cloning, overexpression and one step purification of three DHAP-dependent aldolases: rhamnulose-1-phosphate aldolase, fuculose-1-phosphate aldolase and tagatose-1,6-diphosphate aldolase. Bioorg Med Chem 3:945–953CrossRefPubMedGoogle Scholar
  29. Gefflaut T, Blonski C, Perie J, Willson M (1995) Class I aldolases: substrate specificity, mechanism, inhibitors and structural aspects. Prog Biophys Mol Biol 63:301–340CrossRefPubMedGoogle Scholar
  30. Gijsen HJM, Wong CH (1994) Unprecedented asymmetric aldol reactions with three aldehydes substrates catalyzed by 2-deoxyribose-5-phosphate aldolase. J Am Chem Soc 116:8422–8423CrossRefGoogle Scholar
  31. Gijsen HJM, Wong CH (1995) Sequential one-pot aldol reactions catalyzed by 2-deoxyribose-5-phosphate aldolase and fructose-1,6-bisphosphate aldolase. J Am Chem Soc 117:2947–2948CrossRefGoogle Scholar
  32. Gonzalez-Garcia E, Helaine V, Klein G, Schuermann M, Sprenger GA, Fessner WD, Reymond JL (2003) Fluorogenic stereochemical probes for transaldolases. Chem Eur J 9:893–899CrossRefGoogle Scholar
  33. Greenberg WA, Varvak A, Hanson SR, Wong K, Huang H, Chen P, Burk MJ (2004) Development of an efficient, scalable, aldolase-catalyzed process for the enantioselective synthesis of statin intermediates. Proc Natl Acad Sci U S A 101:5788–5793CrossRefPubMedGoogle Scholar
  34. Griffiths JS, Cheriyan M, Corbell JB, Pocivavsek L, Fierke CA, Toone EJ (2004) A bacterial selection for the directed evolution of pyruvate aldolases. Bioorg Med Chem 12:4067–4074CrossRefPubMedGoogle Scholar
  35. Guanti G, Banfi L, Zannetti MT (2000) Phosphonic derivatives of carbohydrates: chemoenzymatic synthesis. Tetrahedron Lett 41:3181–3185CrossRefGoogle Scholar
  36. Guanti G, Zannetti MT, Banfi L, Riva R (2001) Enzymatic resolution of acetoxyalkenylphosphonates and their exploitation in the chemoenzymatic synthesis of phosphonic derivatives of carbohydrates. Adv Synth Catal 343:682–691CrossRefGoogle Scholar
  37. Hao J, Berry A (2004) A thermostable variant of fructose bisphosphate aldolase constructed by directed evolution also shows increased stability in organic solvents. Protein Eng Des Sel 17:689–697CrossRefPubMedGoogle Scholar
  38. Hara H, Masai E, Miyauchi K, Katayama Y, Fukuda M (2003) Characterization of the 4-carboxy-4-hydroxy-2-oxoadipate aldolase gene and operon structure of the protocatechuate 4,5-cleavage pathway genes in Sphingomonas paucimobilis SYK-6. J Bacteriol 185:41–50CrossRefPubMedGoogle Scholar
  39. Henderson DP, Cotterill IC, Shelton MC, Toone EJ (1998) 2-keto-3-deoxy-6-phosphogalactonate aldolase as a catalyst for stereocontrolled carbon–carbon bond formation. J Org Chem 63:906–907CrossRefGoogle Scholar
  40. Hernaez MJ, Floriano B, Rios JJ, Santero E (2002) Identification of a hydratase and a class II aldolase involved in biodegradation of the organic solvent tetralin. Appl Environ Microbiol 68:4841–4846CrossRefPubMedGoogle Scholar
  41. Horecker BL, Tsolas O, Lai CY (1972) Aldolases. In: Boyer PD (ed.) The enzymes, vol VII, 3rd edn. Academic, New York, pp 213–258Google Scholar
  42. Horinouchi M, Hayashi T, Yamamoto T, Kudo T (2003) A new bacterial steroid degradation gene cluster in Comamonas testosteroni TA441 which consists of aromatic-compound degradation genes for seco-steroids and 3-ketosteroid dehydrogenase genes. Appl Environ Microbiol 69:4421–4430PubMedGoogle Scholar
  43. Hsu CC, Hong ZY, Wada M, Franke D, Wong CH (2005) Directed evolution of D-sialic acid aldolase to L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase. Proc Natl Acad Sci U S A 102:9122–9126CrossRefPubMedGoogle Scholar
  44. Inoue K, Widada J, Nakai S, Endoh T, Urata M, Ashikawa Y, Shintani M, Saiki Y, Yoshida T, Habe H, Omori T, Nojiri H (2004) Divergent structures of carbazole degradative car operons isolated from Gram-negative bacteria. Biosci Biotechnol Biochem 68:1467–1480CrossRefPubMedGoogle Scholar
  45. Joerger AC, Mayer S, Fersht AR (2003) Mimicking natural evolution in vitro: an N-acetylneuraminate lyase mutant with an increased dihydrodipicolinate synthase activity. Proc Natl Acad Sci U S A 100:5694–5699CrossRefPubMedGoogle Scholar
  46. Keck A, Rau J, Reemtsma T, Mattes R, Stolz A, Klein J (2002) Identification of quinoide redox mediators that are formed during the degradation of naphthalene-2-sulfonate by Sphingomonas xenophaga BN6. Appl Environ Microbiol 68:4341–4349CrossRefPubMedGoogle Scholar
  47. Kimura T, Vassilev VP, Shen GJ, Wong CH (1997) Enzymatic synthesis of beta-hydroxy-alpha-amino acids based on recombinant D- and L-threonine aldolases. J Am Chem Soc 119:11734–11742CrossRefGoogle Scholar
  48. Koeller KM, Wong CH (2001) Enzymes for chemical synthesis. Nature 409:232–240CrossRefPubMedGoogle Scholar
  49. Kragl U, Gygax D, Ghisalba O, Wandrey C (1991) Enzymatic two step N-acetylneuraminic acid synthesis in enzyme membrane reactor. Angew Chem Int Ed Engl 30:827–828CrossRefGoogle Scholar
  50. Lamble HJ, Heyer NI, Bull SD, Hough DW, Danson MJ (2003) Metabolic pathway promiscuity in the archaeon Sulfolobus solfataricus revealed by studies on glucose dehydrogenase and 2-keto-3-deoxygluconate aldolase. J Biol Chem 278:34066–34072CrossRefPubMedGoogle Scholar
  51. Lamble HJ, Theodossis A, Milburn CC, Taylor GL, Bull SD, Hough DW, Danson MJ (2005a) Promiscuity in the part-phosphorylative Entner–Doudoroff pathway of the archaeon Sulfolobus solfataricus. FEBS Lett 579:6865–6869CrossRefPubMedGoogle Scholar
  52. Lamble HJ, Danson MJ, Hough DW, Bull SD (2005b) Engineering stereocontrol into an aldolase-catalysed reaction. Chem Commun 124–126Google Scholar
  53. Lee JO, Yi JK, Lee SG, Takahashi S, Kim BG (2004) Production of N-acetylneuraminic acid from N-acetylglucosamine and pyruvate using recombinant human renin binding protein and sialic acid aldolase in one pot. Enzyme Microb Technol 35:121–125CrossRefGoogle Scholar
  54. Lin CC, Moris-Varas F, Weitz-Schmidt G, Wong CH (1999) Synthesis of sialyl Lewis x mimetics as selectin inhibitors by enzymatic aldol condensation reactions. Bioorg Med Chem 7:425–433CrossRefPubMedGoogle Scholar
  55. Liu J, Wong CH (2002) Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem Int Ed Engl 41:1404–1407CrossRefGoogle Scholar
  56. Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (2000a) Diversity of microbial threonine aldolases and their applications. J Mol Catal 10:107–115CrossRefGoogle Scholar
  57. Liu JQ, Odani M, Yasuoka T, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (2000b) Gene cloning and overproduction of low-specificity D-threonine aldolase from Alcaligenes xylosoxidans and its application for production of a key intermediate for parkinsonism drug. Appl Microbiol Biotechnol 54:44–51CrossRefPubMedGoogle Scholar
  58. Liu Z, Yang H, Huang Z, Zhou P, Liu SJ (2002) Degradation of aniline by newly isolated, extremely aniline-tolerant Delftia sp. AN3. Appl Microbiol Biotechnol 58:679–682CrossRefPubMedGoogle Scholar
  59. Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S (2003) A novel enzyme, D-3-hydroxyaspartate aldolase from Paracoccus denitrificans IFO 13301: purification, characterization, and gene cloning. Appl Microbiol Biotechnol 62:53–60CrossRefPubMedGoogle Scholar
  60. Liu JJ, Hsu CC, Wong CH (2004): Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin. Tetrahedron Lett 45:2439–2441CrossRefGoogle Scholar
  61. Lorentzen E, Pohl E, Zwart P, Stark A, Russell RB, Knura T, Hensel R, Siebers B (2003) Crystal structure of an archaeal Class I aldolase and the evolution of (βα)8 barrel proteins. J Biol Chem 278:47253–47260CrossRefPubMedGoogle Scholar
  62. Machajewski TD, Wong CH (2000) The catalytic asymmetric aldol reaction. Angew Chem Int Ed Engl 39:1352–1374CrossRefPubMedGoogle Scholar
  63. Marsh JJ, Lebherz HG (1992) Fructose-bisphosphate aldolases: an evolutionary history. Trends Biochem Sci 17:110–113CrossRefPubMedGoogle Scholar
  64. Meyerhof O, Lohmann K, Schuster P (1936) Über die Aldolase, ein Kohlenstoff-verknüpfendes Ferment. Biochem Z 286:319–335Google Scholar
  65. Misono H, Maeda M, Tuda K, Ueshima S, Miyazaki N, Nagata S (2005) Characterization of an inducible phenylserine aldolase from Pseudomonas putida 24-1. Appl Environ Microbiol 71:4602–4609CrossRefPubMedGoogle Scholar
  66. Mitchell M, Qaio L, Wong CH (2001) Chemical-enzymatic synthesis of iminocyclitol phosphonic acids. Adv Synth Catal 343:596–599CrossRefGoogle Scholar
  67. Miyazaki T, Sato H, Sakakibara T, Kajihara Y (2000) An approach to the precise chemoenzymatic synthesis of 13C-labeled sialyloligosaccharide on an intact glycoprotein: a novel one-pot [3-13C]-labeling method for sialic acid analogues by control of the reversible aldolase reaction, enzymatic synthesis of [3-13C]-NeuAc-α-(2→3)-[U-13C]-Gal-β-(1→4)-GlcNAc-β-sequence onto glycoprotein, and its conformational analysis by developed NMR technique. J Am Chem Soc 122:5678–5694CrossRefGoogle Scholar
  68. Muraki T, Taki M, Hasegawa Y, Iwaki H, Lau PCK (2003) Prokaryotic homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase in the 2-nitrobenzoate degradation pathway of Pseudomonas fluorescens strain KU-7. Appl Environ Microbiol 69:1564–1572CrossRefPubMedGoogle Scholar
  69. Murphy CD, O’Hagan D, Schaffrath C (2001) Identification of a PLP-dependent threonine transaldolase: a novel enzyme involved in 4-fluorothreonine biosynthesis in Streptomyces cattleya. Angew Chem Int Ed Engl 113:4611–4613CrossRefGoogle Scholar
  70. Ozaki A, Toone EJ, von der Osten CH, Sinskey AJ, Whitesides GM (1990) Overproduction and substrate specificity of a bacterial fuculose-1-phosphate aldolase: a new enzymatic catalyst for stereocontrolled aldol condensation. J Am Chem Soc 112:4970–4971CrossRefGoogle Scholar
  71. Paiardini A, Contestabile R, D’Aguanno S, Pascarella S, Bossa F (2003) Threonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes. Biochim Biophys Acta 1647:214–219PubMedGoogle Scholar
  72. Phung AN, Zannetti MT, Whited G, Fessner WD (2003) Stereospecific biocatalytic synthesis of pancratistatin analogues. Angew Chem Int Ed Engl 42:4821–4824CrossRefPubMedGoogle Scholar
  73. Ran N, Draths KM, Frost JW (2004) Creation of a shikimate pathway variant. J Am Chem Soc 126:6856–6857CrossRefPubMedGoogle Scholar
  74. Romero A, Wong CH (2000) Chemo-enzymatic total synthesis of 3-epiaustraline, australine, and 7-epialexine. J Org Chem 65:8264–8268CrossRefPubMedGoogle Scholar
  75. Rose IA, O’Connell EL (1969) Studies on the interaction of aldolase with substrate analogues. J Biol Chem 244:124–134Google Scholar
  76. Rutter WJ (1964) Evolution of aldolase. Fed Proc 23:1248–1257PubMedGoogle Scholar
  77. Sánchez-Moreno I, García-García JF, Bastida A, García-Junceda E (2004) Multienzyme system for dihydroxyacetone phosphate-dependent aldolase catalyzed C–C bond formation from dihydroxyacetone. Chem Commun 1634–1635Google Scholar
  78. Schoevaart R, van Rantwijk F, Sheldon RA (1999) Carbohydrates from glycerol: an enzymatic four-step, one-pot synthesis. Chem Commun 2465–2466Google Scholar
  79. Schoevaart R, van Rantwijk F, Sheldon RA (2000a) Stereochemistry of nonnatural aldol reactions catalyzed by DHAP aldolases. Biotechnol Bioeng 70:349–352CrossRefPubMedGoogle Scholar
  80. Schoevaart R, van Rantwijk F, Sheldon RA (2000b) A four-step enzymatic cascade for the one-pot synthesis of non-natural carbohydrates from glycerol. J Org Chem 65:6940–6943CrossRefPubMedGoogle Scholar
  81. Schofield LR, Anderson BF, Patchett ML, Norris GE, Jameson GB, Parker EJ (2005) Substrate ambiguity and crystal structure of Pyrococcus furiosus 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase: an ancestral 3-deoxyald-2-ulosonate-phosphate synthase? Biochemistry 44:11950–11962CrossRefPubMedGoogle Scholar
  82. Schörken U (1997) Untersuchungen zu Struktur und Funktion von Transketolase und Transaldolase, sowie biochemische Charakterisierung der Enzyme aus Escherichia coli. Ph.D. dissertation, University of Düsseldorf, Germany. Jül-Bericht 3418Google Scholar
  83. Schürmann M, Sprenger GA (2001) Fructose-6-phosphate aldolase is a novel class I aldolase from Escherichia coli and is related to a novel group of bacterial transaldolases. J Biol Chem 276:11055–11061CrossRefPubMedGoogle Scholar
  84. Schürmann M, Schürmann M, Sprenger GA (2002) Fructose 6-phosphate aldolase and 1-deoxy-D-xylulose 5-phosphate synthase from Escherichia coli as tools in enzymatic synthesis of 1-deoxy sugars. J Mol Catal B Enzym 19–20:247–252CrossRefGoogle Scholar
  85. Schuster M, He WF, Blechert S (2001) Chemical-enzymatic synthesis of azasugar phosphonic acids as glycosyl phosphate surrogates. Tetrahedron Lett 42:2289–2291CrossRefGoogle Scholar
  86. Shelton MC, Cotterill IC, Novak STA, Poonawala RM, Sudarshan S, Toone EJ (1996) 2-Keto-3-deoxy-6-phosphogluconate aldolases as catalysts for stereocontrolled carbon–carbon bond formation. J Am Chem Soc 118:2117–2125CrossRefGoogle Scholar
  87. Siebers B, Brinkmann H, Dörr C, Tjaden B, Lilie H, van der Oost J, Verhees CH (2001) Archaeal fructose-1,6-bisphosphate aldolase constitutes a new family of archaeal type Class I aldolase. J Biol Chem 276:28710–28718CrossRefPubMedGoogle Scholar
  88. Silvestri MG, Desantis G, Mitchell M, Wong CH (2003) Asymmetric aldol reactions using aldolases. Top Stereochem 23:267–342CrossRefGoogle Scholar
  89. Soderberg T, Alver RC (2004) Transaldolase of Methanocaldococcus jannaschii. Archaea 1:255–262PubMedCrossRefGoogle Scholar
  90. Sprenger GA, Schörken U, Sprenger G, Sahm H (1995) Transaldolase B of Escherichia coli K-12: Cloning of its gene, talB, and characterization of the enzyme from recombinant strains. J Bacteriol 177:5930–5936PubMedGoogle Scholar
  91. Straub A, Effenberger F, Fischer P (1990) Aldolase-catalyzed C–C bond formation for stereoselective synthesis of nitrogen-containing carbohydrates. J Org Chem 55:3926–3932CrossRefGoogle Scholar
  92. Sugiyama M, Suzuki S-I, Tonouchi N, Yokozeki K (2003) Transaldolase/glucose-6-phosphate isomerase bifunctional enzyme and ribulokinase as factors to increase xylitol production from D-arabitol in Gluconobacter oxydans. Biosci Biotechnol Biochem 67:2524–2532CrossRefPubMedGoogle Scholar
  93. Sukumaran J, Hanefeld U (2005) Enantioselective C–C bond synthesis catalysed by enzymes. Chem Soc Rev 34:530–542CrossRefPubMedGoogle Scholar
  94. Sundaram AK, Woodard RW (2000) Probing the stereochemistry of E. coli 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (phenylalanine-sensitive)-catalyzed synthesis of KDO 8-P analogues. J Org Chem 65:5891–5897CrossRefPubMedGoogle Scholar
  95. Takayama S, McGarvey GJ, Wong CH (1997) Microbial aldolases and transketolases: new biocatalytic approaches to simple and complex sugars. Annu Rev Microbiol 51:285–310CrossRefPubMedGoogle Scholar
  96. Thomson GJ, Howlett GJ, Ashcroft AE, Berry A (1998) The dhnA gene of Escherichia coli encodes a Class I fructose bisphosphate aldolase. Biochem J 331:437–445PubMedGoogle Scholar
  97. Thorell S, Schürmann M, Sprenger GA, Schneider G (2002) Crystal structure of decameric fructose-6-phosphate aldolase from Escherichia coli reveals inter-subunit helix swapping as a structural basis for assembly differences in the transaldolase family. J Mol Biol 319:161–171CrossRefPubMedGoogle Scholar
  98. Toone EJ, Whitesides GM (1991) Enzymes as catalysts in carbohydrate synthesis. In: Bednarski MD, Simon ES (eds) ACS Symposium Series 466. ACS, Washington, D.C.Google Scholar
  99. Toone EJ, Kobori Y, Myles DC, Ozaki A, Schmid W, von der Osten C, Sinskey AJ, Whitesides GM (1990) Enzymes as catalysts in carbohydrate synthesis. In: Baldwin TO (ed) Chemical aspects of enzyme biotechnology. Plenum, New York, pp 179–195Google Scholar
  100. Wada M, Hsu C-C, Franke D, Mitchell M, Heine A, Wilson I, Wong C-H (2003) Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions. Bioorganic Med Chem 11:2091–2098CrossRefGoogle Scholar
  101. Williams GJ, Domann S, Nelson A, Berry A (2003) Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution. Proc Natl Acad Sci U S A 100:3143–3148CrossRefPubMedGoogle Scholar
  102. Wong CH (1995) Enzymatic and chemoenzymatic synthesis of carbohydrates. Pure Appl Chem 67:1609–1616Google Scholar
  103. Wong C-H, Whitesides GM (1983) Synthesis of sugars by aldolase-catalyzed condensation reactions. J Org Chem 48:3199–3205CrossRefGoogle Scholar
  104. Wong CH, Halcomb RL, Ichikawa Y, Kajimoto T(1995) Enzymes in organic synthesis: application to the problems of carbohydrate recognition (part 2). Angew Chem Int Ed Engl 34:412–432CrossRefGoogle Scholar
  105. Woodhall T, Williams G, Berry A, Nelson A (2005) Creation of a tailored aldolase for the parallel synthesis of sialic acid mimetics. Angew Chem Int Ed Engl 117: 2147–2150CrossRefGoogle Scholar
  106. Wymer N, Buchanan LV, Henderson D, Mehta N, Botting CH, Pocivavsek L, Fierke CA, Toone EJ, Naismith JH (2001) Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli. Structure 9:1–9CrossRefPubMedGoogle Scholar
  107. Yoshida KI, Yamaguchi M, Ikeda H, Omae K, Tsurusaki KI, Fujita Y (2004) The fifth gene of the iol operon of Bacillus subtilis, iolE, encodes 2-keto-myo-inositol dehydratase. Microbiology 150:571–580CrossRefPubMedGoogle Scholar
  108. Zannetti MT, Walter C, Knorst M, Fessner WD (1999) Fructose 1,6-bisphosphate aldolase from Staphylococcus carnosus: overexpression, structure prediction, stereoselectivity, and application in the synthesis of bicyclic sugars. Chem Eur J 5:1882–1890CrossRefGoogle Scholar
  109. Zhu W, Li Z (2000) Synthesis of perfluoroalkylated sugars catalyzed by rabbit muscle aldolase (RAMA). J Chem Soc Perkin Trans 1:1105–1108CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Institut für MikrobiologieUniversität StuttgartStuttgartGermany

Personalised recommendations