The goal of the proposed research program is to provide a detailed understanding of the biosynthesis of aromatic amino acids and growth factors from chorismate in bacteria. These biosynthetic pathways of primary metabolism are unique to the plant kingdom. The biosynthesis of tyrosine, anthranilate (precursor to tryptophan), and isochorismate (precursor to 2,3-dihydroxybenzoate and m-carboxyaromatic amino acids) are of principle interest. The synthesis of numerous substances for investigation of the enzyme- catalyzed pathways will be accomplished. These substances will be utilized in collaboration with Professor C.T. Walsh (Harvard Medical School) to elucidate mechanistic details of anthranilate, p-aminobenzoate, isochorismate, and 2,3-dihydroxybenzoate biosynthesis. In noncollaborative efforts the substances will be utilized to elucidate the mechanistic details of tyrosine and isochorismate biosynthesis from chorismate. A final objective of the program is the discovery of analogs of biosynthetic intermediates that will be useful antibacterial agents or antifungal agents by selective inhibition of target enzymes in the chorismate pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031958-08
Application #
3280406
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139