INVESTIGATIONS OF THE CHORISMATE PATHWAY

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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.