Design and Development of Enzymatic Organic Synthesis

  • C.-H. Wong
Part of the Industry-University Cooperative Chemistry Program Symposia book series (IUCC)


The rate acceleration and selectivity of various enzymatic reactions operated under mild conditions are the major attractive features of enzymes for use as catalysts in organic synthesis. Many natural and unnatural enzymatic reactions have been demonstrated for multigram scale synthesis of chiral organic molecules1. The number of enzymes isolated (about 2,500), however, only represents approximately 2% of the total number of enzymes which may exist in nature. So far, there have been only about 50 enzymes exploited for use in organic synthesis. With an increasing number of enzymes available, the synthetic methods based on enzyme catalysis are being extended from the preparation of small chiral molecules to the synthesis of more complex molecules such as oligosaccharides, polypeptides, nucleotides and their conjugates. This review describes the most recent developments in my laboratory in this area with emphasis on the synthesis of carbohydrates and polypeptides.


Aldol Reaction Dihydroxyacetone Phosphate Amidase Activity Diethyl Acetal Amide Hydrolysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C.-H. Wong, Enzymatic catalysts in organic synthesis, Science 244:1145 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    M.D. Bednarski, E.S. Simon, N. Bischofberger, W-D. Fessner, M.J. Kim, W. Lees, T. Saito, H. Waldmann, G.M. Whitesides, Rabbit muscle aldolase as a catalyst in organic synthesis, J. Am. Chem. Soc. 111:627 (1989).CrossRefGoogle Scholar
  3. 3.
    C.H. von der Osten, A.J. Sinskey, C.F. Barbas, III, R.L. Pederson, Y.-F. Wang, C.-H. Wong, Use of a recombinant bacterial fructose-1,6-diphosphate aldolase in aldol reactions, J. Am. Chem. Soc. 111:3924 (1989).CrossRefGoogle Scholar
  4. 4.
    P.R. Alefounder, S.A. Baldwin, R.N. Perham, N.J. Short, Cloning, sequence analysis and over-expression of the gene for the class II fructose-1,6-biphosphate aldolase of E. coli, Biochem. J. 257:529 (1989).PubMedGoogle Scholar
  5. 5.
    Y.L. Chen, Metalloenzyme chemistry, Ph.D. Thesis, Texas A&M University (1989).Google Scholar
  6. 6.
    C.F. Barbas, III, Y.-F. Wang, C.-H. Wong, Deoxyribose 5-phosphate aldolase as a synthetic catalyst, J. Am. Chem. Soc. 112:2013 (1990).CrossRefGoogle Scholar
  7. 7.
    C.-H. Wong, S.-T. Chen, W.J. Hennen, J.A. Bibbs, Y.-F. Wang, J.L.-C. Liu, M.W. Pantoliano, M. Whitlow, P.N. Bryan, Enzymes in organic synthesis: use of subtilisin and a highly stable mutant derived from multiple site-specific mutations, J. Am. Chem. Soc. 112:945 (1990).CrossRefGoogle Scholar
  8. 8.
    C.F. Barbas, III, C.-H. Wong, Papain catalyzed peptide synthesis: control of amidase activity and the introduction of unusual amino acids, J. Chem. Soc. Chem. Comm. 532-534 (1987).Google Scholar
  9. 9.
    J.B. West, C.-H. Wong, Use of nonproteases in peptide synthesis, Tetrahedron Lett. 28:1629 (1987).CrossRefGoogle Scholar
  10. 10.
    A.L. Margolin, A.M. Klibanov, Peptide synthesis catalyzed by lipases in anhydrous organic solvents, J. Am. Chem. Soc. 109:3802 (1987).CrossRefGoogle Scholar
  11. 11.
    CF. Barbas, III, J.R. Matos, J.B. West, C.-H. Wong, A search for peptide ligase: cosolvent-mediated conversion of proteases to esterases for irreversible synthesis of peptides, J. Am. Chem. Soc. 110:5162 (1988).CrossRefGoogle Scholar
  12. 12.
    J.B. West, W.J. Hennen, J.L. Lalonde, J.A. Bibbs, Z. Zhong, E.F. Meyer, C.-H. Wong, Enzymes as synthetic catalysts: mechanistic and active-site considerations of natural and modified chymotrypsin, J. Am. Chem. Soc., in press.Google Scholar
  13. 13.
    J.B. West, J. Scholten, N.J. Stolowich, J.L. Hogg, A.I. Scott, C-H. Wong, Modification of proteases to esterases for peptide synthesis: methylchymotrypsin, J. Am. Chem. Soc. 110:3709 (1988).CrossRefGoogle Scholar
  14. 14.
    R. Henderson, Catalytic activity of oc-chymotrypsin in which histidine-57 has been methylated, Biochem. J. 124:13 (1971).PubMedGoogle Scholar
  15. 15.
    L.D. Byers, D.E. Koshland, Jr., On the mechanism of action of methyl chymotrypsin, Bioorganic Chemistry 7:15 (1978).CrossRefGoogle Scholar
  16. 16.
    J.D. Scholten, J.L. Hogg, F.M. Raushel, Methyl chymotrypsin catalyzed hydrolyses of specific substrate esters indicate multiple proton catalysis is possible with a modified charge relay triad, J. Am. them. Soc. 110:8246 (1988).CrossRefGoogle Scholar
  17. 17.
    J. Rebek, Jr., Recognition and catalysis using molecular clefts, Chemtracts — Organic chemistry 2:337 (1989).Google Scholar
  18. 18.
    T. Nakatsuka, T. Sasaki, E.T. Kaiser, Peptide segment coupling catalyzed by the semisynthetic enzyme subtilisin, J. Am. Chem. Soc. 109:3808 (1987).CrossRefGoogle Scholar
  19. 19.
    Z.-P. Wu, D. Hilvert, Conversion of a protease into an acyl transferase: selenosubtilisin, J. Am. Chem. Soc. 111:4513 (1989).CrossRefGoogle Scholar
  20. 20.
    F. Widmer, K. Breddam, J.T. Johansen, Carboxypeptidase Y catalyzed peptide synthesis using amino acid alkyl esters as amine components, Carlsberg Res. Comm. 45:453 (1980).CrossRefGoogle Scholar
  21. 21.
    H. Nakajima, S. Kitabatake, R. Tsurutani, K. Yamamoto, I. Tomioka, K. Imahori, Peptide synthesis catalyzed by aminoacyl-tRNA synthetases from Bacillus stearothermophilus, Int. J. Peptide Protein Res. 28:179 (1986).CrossRefGoogle Scholar
  22. 22.
    W.D. Huse, L. Sastry, S.A. Iverson, A.S. Kang, M. Alting-Mees, D.R. Burton, S.J. Benkovic, R.A. Lerner, Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda, Science 246:1275 (1989).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • C.-H. Wong
    • 1
  1. 1.Department of ChemistryResearch Institute of Scripps ClinicLa JollaUSA

Personalised recommendations