INVESTIGATIONS OF THE CHORISMATE PATHWAY

拟议的研究计划的目标是提供一个详细的 对芳香族氨基酸生物合成与生长的认识 细菌中分枝酸的影响因素。这些生物合成途径 初级新陈代谢是植物界独有的。……的生物合成 酪氨酸、邻氨基苯甲酸酯(色氨酸的前体)和异氨基甲酸酯 (2，3-二羟基苯甲酸和间-羧基芳香族氨基酸的前体) 原则性利益。 用于研究该酶的多种物质的合成- 催化途径将被完成。这些物质将被利用 与C.T.沃尔什教授(哈佛医学院)合作 阐明邻氨基苯甲酸酯，对氨基苯甲酸酯， 2，3-二羟基苯甲酸酯的生物合成。在非协作环境中 这些物质将被用来阐明其机理 从分枝酸生物合成酪氨酸和异分枝酸的细节。 该计划的最终目标是发现类似于 生物合成中间体将成为有用的抗菌剂或 选择性抑制体内靶标酶的抗真菌药物 分支酸途径。

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.