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]  Che-Chang Hsu,et al.  Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin , 2004 .

[2]  Chi-Huey Wong,et al.  Unprecedented Asymmetric Aldol Reactions with Three Aldehyde Substrates Catalyzed by 2-Deoxyribose-5-phosphate Aldolase , 1994 .

[3]  G. Schneider,et al.  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. , 2002, Journal of molecular biology.

[4]  Chi‐Huey Wong,et al.  Microbial aldolases and transketolases: new biocatalytic approaches to simple and complex sugars. , 1997, Annual review of microbiology.

[5]  M. Kataoka,et al.  A novel enzyme, d-3-hydroxyaspartate aldolase from Paracoccus denitrificans IFO 13301: purification, characterization, and gene cloning , 2003, Applied Microbiology and Biotechnology.

[6]  Chi‐Huey Wong,et al.  Enzymes in Organic Synthesis: Application to the Problems of Carbohydrate Recognition (Part 1) , 1995 .

[7]  H. Hara,et al.  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 , 2003, Journal of bacteriology.

[8]  Enzymatic C-C bond formation in asymmetric synthesis , 1996 .

[9]  Bernhard Hauer,et al.  Carbon-carbon coupling in biotransformation. , 2003, Current opinion in biotechnology.

[10]  W. Fessner,et al.  Short Enzymatic Synthesis of L‐Fucose Analogs , 2000 .

[11]  M. Lilly,et al.  Alkaline Biocatalysis for the Direct Synthesis of N‐Acetyl‐D‐neuraminic Acid (Neu5Ac) from N‐Acetyl‐D‐glucosamine (GlcNAc) , 2000 .

[12]  J. Marsh,et al.  Fructose-bisphosphate aldolases: an evolutionary history. , 1992, Trends in biochemical sciences.

[13]  J. Bolte,et al.  Rabbit muscle aldolase (RAMA) as a catalyst in a new approach for the synthesis of 3-deoxy-D-manno-2-octulosonic acid and analogues , 2001 .

[14]  J. Périé,et al.  Class I aldolases: substrate specificity, mechanism, inhibitors and structural aspects. , 1995, Progress in biophysics and molecular biology.

[15]  C. Mak,et al.  Directed evolution of D-2-keto-3-deoxy-6-phosphogluconate aldolase to new variants for the efficient synthesis of D- and L-sugars. , 2000, Chemistry & biology.

[16]  E. Toone,et al.  A bacterial selection for the directed evolution of pyruvate aldolases. , 2004, Bioorganic & medicinal chemistry.

[17]  Chi‐Huey Wong,et al.  Asymmetric Aldol Reactions Using Aldolases , 2003 .

[18]  S. David.  Enzymatic Synthesis of a Branched‐Chain Hexulose: 5‐Deoxy‐5‐C‐hydroxymethyl‐β‐L‐xylo‐hex‐2‐ulopyranose , 1999 .

[19]  E. Toone,et al.  Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli. , 2001, Structure.

[20]  Fructose 6-phosphate aldolase and 1-deoxy-d-xylulose 5-phosphate synthase from Escherichia coli as tools in enzymatic synthesis of 1-deoxysugars , 2002 .

[21]  Y. Fujita,et al.  The fifth gene of the iol operon of Bacillus subtilis, iolE, encodes 2-keto-myo-inositol dehydratase. , 2004, Microbiology.

[22]  G. Whitesides,et al.  Overproduction and substrate specificity of a bacterial fuculose-1-phosphate aldolase: a new enzymic catalyst for stereocontrolled aldol condensation , 1990 .

[23]  J. B. Jones,et al.  Enzymes in organic synthesis-29 : Preparations of enantiomerically pure cis -2,3- and 2,4-dimethyl lactones via horse liver alcohol dehydrogenase-catalyzed oxidations☆☆☆ , 1984 .

[24]  Chi‐Huey Wong,et al.  Enzymes in Organic Synthesis: Application to the Problems of Carbohydrate Recognition. Part 2. , 1995 .

[25]  J. Tsuji,et al.  Palladium-catalyzed telomerization of butadiene with ammonia , 1980 .

[26]  I. Wilson,et al.  Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions. , 2003, Bioorganic & medicinal chemistry.

[27]  E. García-Junceda,et al.  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. , 1995, Bioorganic & medicinal chemistry.

[28]  J. B. Jones.  Enzymes in Organic Synthesis , 1986 .

[29]  F. Effenberger,et al.  Aldolase-catalyzed C-C bond formation for stereoselective synthesis of nitrogen-containing carbohydrates , 1990 .

[30]  G. Sprenger,et al.  Fructose-6-phosphate Aldolase Is a Novel Class I Aldolase from Escherichia coli and Is Related to a Novel Group of Bacterial Transaldolases* , 2001, The Journal of Biological Chemistry.

[31]  M. Kula,et al.  Fructose-1,6-Bisphosphate Aldolases from Staphylococcus Carnosus: Stereoselective Enzymatic Synthesis of Ketose-1-Phosphates and Successive Reaction to 1,3-Dioxanes , 2001 .

[32]  Chi‐Huey Wong,et al.  Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. , 2002, Angewandte Chemie.

[33]  B. Anderson,et al.  Substrate ambiguity and crystal structure of Pyrococcus furiosus 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase: an ancestral 3-deoxyald-2-ulosonate-phosphate synthase? , 2005, Biochemistry.

[34]  N. Tonouchi,et al.  Transaldolase/Glucose-6-phosphate Isomerase Bifunctional Enzyme and Ribulokinase as Factors to Increase Xylitol Production from D-Arabitol in Gluconobacter oxydans , 2003, Bioscience, biotechnology, and biochemistry.

[35]  R. Sheldon,et al.  Stereochemistry of nonnatural aldol reactions catalyzed by DHAP aldolases. , 2000, Biotechnology and bioengineering.

[36]  G. Whitesides,et al.  Synthesis of sugars by aldolase-catalyzed condensation reactions , 1983 .

[37]  E. Toone,et al.  2-KETO-3-DEOXY-6-PHOSPHOGLUCONATE ALDOLASES AS CATALYSTS FOR STEREOCONTROLLED CARBON-CARBON BOND FORMATION , 1996 .

[38]  P. Lau,et al.  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 , 2003, Applied and Environmental Microbiology.

[39]  B. Yoon,et al.  Toluene degradation pathway from Pseudomonas putida F1: substrate specificity and gene induction by 1-substituted benzenes , 2000, Journal of Industrial Microbiology and Biotechnology.

[40]  F. Morís-Varas,et al.  Synthesis of sialyl Lewis x mimetics as selectin inhibitors by enzymatic aldol condensation reactions. , 1999, Bioorganic & medicinal chemistry.

[41]  C. Wong,et al.  Enzymic aldol condensation/isomerization as a route to unusual sugar derivatives. , 1986, Journal of the American Chemical Society.

[42]  H. Yamada,et al.  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 , 2000, Applied Microbiology and Biotechnology.

[43]  Byung-Gee Kim,et al.  Production of N-acetylneuraminic acid from N-acetylglucosamine and pyruvate using recombinant human renin binding protein and sialic acid aldolase in one pot , 2004 .

[44]  Creation of a shikimate pathway variant. , 2004, Journal of the American Chemical Society.

[45]  A. Fersht,et al.  Mimicking natural evolution in vitro: An N-acetylneuraminate lyase mutant with an increased dihydrodipicolinate synthase activity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Udo Kragl,et al.  Enzymatic Two‐Step Synthesis of N‐Acetyl‐neuraminic Acid in the Enzyme Membrane Reactor , 1991 .

[47]  Gavin J. Williams,et al.  Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[48]  J. Bolte,et al.  Transketolase and fructose-1,6-bis-phosphate aldolase, complementary tools for access to new ulosonic acid analogues , 2004 .

[49]  J. Badia,et al.  Diastereoselective Enzymatic Aldol Additions: L‐Rhamnulose and L‐Fuculose 1‐Phosphate Aldolases from E. coli , 1991 .

[50]  Z. Huang,et al.  Degradation of aniline by newly isolated, extremely aniline-tolerant Delftia sp. AN3 , 2002, Applied Microbiology and Biotechnology.

[51]  W. Rutter,et al.  EVOLUTION OF ALDOLASE. , 1964, Federation proceedings.

[52]  F. Effenberger,et al.  Enzyme-catalyzed reactions. Part 4. Aldolase-catalyzed carbon-carbon bond formation for stereoselective synthesis of nitrogen containing carbohydrates , 1990 .

[53]  E. Toone,et al.  Pyruvate aldolases as reagents for stereospecific aldol condensation , 1992 .

[54]  S. Nakai,et al.  Divergent Structures of Carbazole Degradative car Operons Isolated from Gram-negative Bacteria , 2004, Bioscience, biotechnology, and biochemistry.

[55]  Alexander Varvak,et al.  Development of an efficient, scalable, aldolase-catalyzed process for enantioselective synthesis of statin intermediates. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Chi‐Huey Wong,et al.  Enzymatic Synthesis of β-Hydroxy-α-amino Acids Based on Recombinant d- and l-Threonine Aldolases , 1997 .

[57]  Chi-Huey Wong,et al.  Deoxyribose-5-phosphate aldolase as a synthetic catalyst , 1990 .

[58]  Tim Soderberg,et al.  Transaldolase of Methanocaldococcus jannaschii. , 2004, Archaea.

[59]  G. Whitesides,et al.  Enzymes as Catalysts in Carbohydrate Synthesis , 1990 .

[60]  E. Toone,et al.  2-Keto-3-deoxy-6-phosphogalactonate Aldolase as a Catalyst for Stereocontrolled Carbon−Carbon Bond Formation , 1998 .

[61]  Chi‐Huey Wong,et al.  One-pot synthesis of L-Fructose using coupled multienzyme systems based on rhamnulose-1-phosphate aldolase. , 2003, The Journal of organic chemistry.

[62]  W. Fessner.  Enzyme mediated C-C bond formation. , 1998, Current opinion in chemical biology.

[63]  Chi‐Huey Wong,et al.  The Catalytic Asymmetric Aldol Reaction , 2000 .

[64]  Wolf-Dieter Fessner,et al.  “Artificial Metabolisms” for the Asymmetric One-Pot Synthesis of Branched-Chain Saccharides†‡ , 1992 .

[65]  Chi‐Huey Wong,et al.  SEQUENTIAL ONE-POT ALDOL REACTIONS CATALYZED BY 2-DEOXYRIBOSE-5-PHOSPHATE ALDOLASE AND FRUCTOSE-1,6-DIPHOSPHATE ALDOLASE , 1995 .

[66]  Wei Zhu,et al.  Synthesis of perfluoroalkylated sugars catalyzed by rabbit muscle aldolase (RAMA) , 2000 .

[67]  U. Hanefeld,et al.  Enantioselective C-C bond synthesis catalysed by enzymes. , 2005, Chemical Society reviews.

[68]  Threonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes. , 2003, Biochimica et biophysica acta.

[69]  Chi-Huey Wong,et al.  Structure-based mutagenesis approaches toward expanding the substrate specificity of D-2-deoxyribose-5-phosphate aldolase. , 2003, Bioorganic & medicinal chemistry.

[70]  Che-Chang Hsu,et al.  Directed evolution of D-sialic acid aldolase to L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[71]  W. Fessner,et al.  Fructose 1,6‐Bisphosphate Aldolase from Staphylococcus carnosus: Overexpression, Structure Prediction, Stereoselectivity, and Application in the Synthesis of Bicyclic Sugars , 1999 .

[72]  F. Raushel,et al.  Chemical Aspects of Enzyme Biotechnology , 1990, Industry-University Cooperative Chemistry Program Symposia.

[73]  J. Joglar,et al.  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 aldehyde. , 2005, Chemistry.

[74]  D. Hough,et al.  An extremely thermostable aldolase from Sulfolobus solfataricus with specificity for non-phosphorylated substrates. , 1999, The Biochemical journal.

[75]  G. Taylor,et al.  Promiscuity in the part‐phosphorylative Entner–Doudoroff pathway of the archaeon Sulfolobus solfataricus , 2005, FEBS letters.

[76]  Chi‐Huey Wong.  Enzymatic and chemo-enzymatic synthesis of carbohydrates , 1995 .

[77]  D. Hough,et al.  Engineering stereocontrol into an aldolase-catalysed reaction. , 2005, Chemical communications.

[78]  F. Bringaud,et al.  Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites. , 2000, Bioorganic & medicinal chemistry.

[79]  A. Ashcroft,et al.  The dhnA gene of Escherichia coli encodes a class I fructose bisphosphate aldolase. , 1998, The Biochemical journal.

[80]  I. A. Rose,et al.  Studies on the interaction of aldolase with substrate analogues. , 1969, The Journal of biological chemistry.

[81]  H. Sahm,et al.  Transaldolase B of Escherichia coli K-12: cloning of its gene, talB, and characterization of the enzyme from recombinant strains , 1995, Journal of bacteriology.

[82]  P. Zwart,et al.  Crystal Structure of an Archaeal Class I Aldolase and the Evolution of (βα)8 Barrel Proteins* , 2003, Journal of Biological Chemistry.

[83]  Narinder I. Heyer,et al.  Metabolic Pathway Promiscuity in the Archaeon Sulfolobus solfataricus Revealed by Studies on Glucose Dehydrogenase and 2-Keto-3-deoxygluconate Aldolase* , 2003, Journal of Biological Chemistry.

[84]  R. Eaton.  trans-o-Hydroxybenzylidenepyruvate Hydratase-Aldolase as a Biocatalyst , 2000, Applied and Environmental Microbiology.

[85]  Chi‐Huey Wong,et al.  Enzymatic Aldol Condensation/Isomerization as a Route to Unusual Sugar Derivatives. , 1987 .

[86]  J. Reymond,et al.  Fluorogenic stereochemical probes for transaldolases. , 2003, Chemistry.

[87]  R. Riva,et al.  Enzymatic Resolution of Acetoxyalkenylphosphonates and Their Exploitation in the Chemoenzymatic Synthesis of Phosphonic Derivatives of Carbohydrates , 2001 .

[88]  T. Kudo,et al.  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 , 2003, Applied and Environmental Microbiology.

[89]  T. Reemtsma,et al.  Identification of Quinoide Redox Mediators That Are Formed during the Degradation of Naphthalene-2-Sulfonate by Sphingomonas xenophaga BN6 , 2002, Applied and Environmental Microbiology.

[90]  H. Brinkmann,et al.  Archaeal Fructose-1,6-bisphosphate Aldolases Constitute a New Family of Archaeal Type Class I Aldolase* , 2001, The Journal of Biological Chemistry.

[91]  C. Murphy,et al.  Identification of a PLP-Dependent Threonine Transaldolase: A Novel Enzyme Involved in 4-Fluorothreonine Biosynthesis in Streptomyces cattleya This work was supported by the Biotechnological and Biological Sciences Research Council and the University of St Andrews. , 2001, Angewandte Chemie.

[92]  S. Blechert,et al.  Chemical-enzymatic synthesis of azasugar phosphonic acids as glycosyl phosphate surrogates , 2001 .

[93]  W. Fessner,et al.  Stereospecific biocatalytic synthesis of pancratistatin analogues. , 2003, Angewandte Chemie.

[94]  Chi‐Huey Wong,et al.  Enzymes for Chemical Synthesis , 2001 .

[95]  Jijun Hao,et al.  A thermostable variant of fructose bisphosphate aldolase constructed by directed evolution also shows increased stability in organic solvents. , 2004, Protein engineering, design & selection : PEDS.

[96]  W. Fessner,et al.  Biocatalytic synthesis of hydroxylated natural products using aldolases and related enzymes. , 2001, Current opinion in biotechnology.

[97]  M. Kataoka,et al.  Diversity of microbial threonine aldolases and their application , 2000 .

[98]  Hiroshi A. Maeda,et al.  Characterization of an Inducible Phenylserine Aldolase from Pseudomonas putida 24-1 , 2005, Applied and Environmental Microbiology.

[99]  E. Santero,et al.  Identification of a Hydratase and a Class II Aldolase Involved in Biodegradation of the Organic Solvent Tetralin , 2002, Applied and Environmental Microbiology.

[100]  Gavin J. Williams,et al.  Creation of a tailored aldolase for the parallel synthesis of sialic acid mimetics. , 2005, Angewandte Chemie.

[101]  Chi‐Huey Wong,et al.  Directed evolution of aldolases. , 2004, Methods in enzymology.