EXCEEDTHE SPACE PROVIDED. Using a combination of organic chemistry, molecular biology, enzymology, and NMR spectroscopy the details of the biosynthesis of uroporphyrinogen III (theprecursor of heme and chlorophyll) and its subsequent transformation to vitamin B12,the anti-perinicious anemia factor, will be elucidated. Knowledge of the pathway including control mechanisms and genetic mapping will define intermediates important in diseases such as B12 deficiency and acute intermittent porphyria. All of the biosynthetic enzymes necessary for the formation of cobyrinic acid, the simplest B12 analog, will be overexpressed using the sequenced cbi genes of Salmonella typhimurium and the cob genes of Pseudomonas denitrificans and their mechanisms studied by NMR spectroscopy via13C- labeling. Finally, the multi-enzyme synthesis of advanced intermediates and of B12 itself will be addressed. PERFORMANCE SITE(S) (organization, city, state) Texas A&M University, College Station, Texas KEY PERSONNEL. See instructions on Page 11. Use continuation pages as needed to provide the required information in the format shown below. Name Organization Role on Project Scott, A. I. Dept. of Chemistry Texas A&M University Roessner, C. A. Dept. of Chemistry Texas A&M University Stolowich, N. J. Dept. of Chemistry Texas A&M University Santander, P. Dept. of Chemistry Texas A&M University Pichon, C. Dept. of Chemistry Texas A&M University Davidson Professor of Science Principal Investigator Senior Enzymologist i Cloning and Expression Senior Research Scientist NMR Spectroscopy/Enzyme mechanism Associate Research Scientist Isolation of Intermediates Associate Research Scientist Synthesis of 13C substrates/Bioconversion Jiminez, M. Dept. of Chemistry Research Assistant Texas A&M University Enzymology PHS 398 (Rev. 5/95) Page 2 * BB Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. ========================================Section End===========================================
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