Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
C.-H. Wong, Enzymatic catalysts in organic synthesis, Science 244:1145 (1989).
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).
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).
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).
Y.L. Chen, Metalloenzyme chemistry, Ph.D. Thesis, Texas A&M University (1989).
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).
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).
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).
J.B. West, C.-H. Wong, Use of nonproteases in peptide synthesis, Tetrahedron Lett. 28:1629 (1987).
A.L. Margolin, A.M. Klibanov, Peptide synthesis catalyzed by lipases in anhydrous organic solvents, J. Am. Chem. Soc. 109:3802 (1987).
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).
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.
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).
R. Henderson, Catalytic activity of oc-chymotrypsin in which histidine-57 has been methylated, Biochem. J. 124:13 (1971).
L.D. Byers, D.E. Koshland, Jr., On the mechanism of action of methyl chymotrypsin, Bioorganic Chemistry 7:15 (1978).
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).
J. Rebek, Jr., Recognition and catalysis using molecular clefts, Chemtracts — Organic chemistry 2:337 (1989).
T. Nakatsuka, T. Sasaki, E.T. Kaiser, Peptide segment coupling catalyzed by the semisynthetic enzyme subtilisin, J. Am. Chem. Soc. 109:3808 (1987).
Z.-P. Wu, D. Hilvert, Conversion of a protease into an acyl transferase: selenosubtilisin, J. Am. Chem. Soc. 111:4513 (1989).
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).
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).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
Wong, CH. (1990). Design and Development of Enzymatic Organic Synthesis. In: Baldwin, T.O., Raushel, F.M., Scott, A.I. (eds) Chemical Aspects of Enzyme Biotechnology. Industry-University Cooperative Chemistry Program Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9637-7_14
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9637-7_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9639-1
Online ISBN: 978-1-4757-9637-7
eBook Packages: Springer Book Archive