In the continuation of our studies on the stereochemistry of enzyme reactions the major focus will be on the steric course of various reactions of one-carbon metabolism and on the mechanism of deoxyhexose formation, with some effort still devoted to the completion of ongoing studies on pyridoxal phosphate enzymes and on the isoprenylation of tryptophan in Claviceps. The studies on one-carbon metabolism will examine stereochemical aspects of DNA methylation, methionine biosynthesis, the formation of the methylenedioxy function and the berberine bridge in alkaloid biosynthesis, and the double methylation involved in thienamycin biosynthesis. In the work on deoxyhexose formation we will study stereochemical and mechanistic aspects of the formation of CDP-3,6-dideoxyglucose from CDP-4-keto-6-deoxyglucose by a pyridoxamine phosphate-dependent enzyme from Salmonella. Exploratory studies will also be carried out on the biosynthesis of 2,6-dideoxyhexoses in Streptomyces and on the stereochemistry of thiamine pyrophosphate-catalyzed enzyme reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM032333-06
Application #
3281076
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Kealey, J T; Lee, S; Floss, H G et al. (1991) Stereochemistry of methyl transfer catalyzed by tRNA (m5U54)-methyltransferase--evidence for a single displacement mechanism. Nucleic Acids Res 19:6465-8
Reynolds, K; Martin, J; Shen, S J et al. (1991) Mechanistic studies of two amino acid racemases of broad substrate specificity from Pseudomonas striata and Aeromonas caviae. J Basic Microbiol 31:177-88
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Frenzel, T; Zhou, P; Floss, H G (1990) Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase. Arch Biochem Biophys 278:35-40
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Otsuka, H; Floss, H G (1987) Steric course of the rhodium-catalyzed decarbonylation of chiral 4-methyl-[1-3H,2-2H1]pentanal. Z Naturforsch C 42:449-54
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