BIOCATALYSIS

John W. Frost

Professor (b. 1955). B.S., 1977, Purdue University, Ph.D., 1981, Massachusetts Institute of Technology. Organic Chemistry. Synthesis and enzymology; biocatalysis; environmental chemistry.

517-355-9715, Ext. 115

frostw@cem.msu.edu

Synthetic chemistry is integrated with the genetic modification of microbes to create novel routes to medicinal natural products and industrial chemicals. D-Glucose, D-xylose, and L-arabinose are the starting materials used in these syntheses.

This synthetic strategy allows microbe-catalyzed conversions of simple carbohydrates to replace the isolation of natural products from exotic sources. Examples include our microbe-catalyzed syntheses of shikimic acid and gallic acid. Prior to this research, shikimic acid was isolated from anise seeds, and gallic acid was obtained from gall nuts. Shikimic acid is the starting material for synthesis of Tamiflu, an antiinfluenza drug. Gallic acid is the starting material used to synthesize trimethoprim, a widely prescribed antibiotic.

Research also endeavors to establish alternatives to benzene-based synthetic chemistry. Rather than use nonrenewable petroleum and carcinogenic benzene, we employ nontoxic carbohydrates derived from plant sources. Examples include our syntheses of hydroquinone, catechol, vanillin and adipic acid. A central feature of these synthetic routes is the elaboration of chemical catalysts and synthetic organic methodology suitable for converting microbe-synthesized metabolites into industrial chemicals.

Representative Publications

Myo-Inositol 1-Phosphate Synthase: Does a Single Active-Site Amino Acid Catalyze Multiple Proton Transfers, F. Tian, M. E. Migaud, and J. W. Frost, J. Am. Chem. Soc., 121, 5795 (1999).

Microbial Synthesis of 3-Dehydroshikimic Acid: A Comparative Analysis of D-Xylose, L-Arabinose, and D-Glucose Carbon Sources, K. Li and J. W. Frost, Biotechnol. Prog., 15, 876 (1999).

Succinic Acid as a Proform of Phosphoenolpyruvic Acid: Employing Glucose Adjuncts in Microbe-Catalyzed Synthesis, K. Li and J. W. Frost, J. Am. Chem. Soc., 121, 9461 (1999).

Synthesis of 1,2,3,4-Tetrahydroxybenzene from D-Glucose: Exploiting myo-Inositol as a Precursor to Aromatic Chemicals, C. A. Hansen, A. B. Dean, K. M. Draths, and J. W. Frost, J. Am. Chem. Soc., 121, 3799 (1999).

Shikimic Acid and Quinic Acid: Replacing Isolation from Plant Sources with Recombinant Microbial Biocatalysis, K. M. Draths, D. R. Knop, and J. W. Frost, J. Am. Chem. Soc., 121, 1603 (1999).