Shikimate Pathway Variants

描述(由申请人提供)：一些更有趣的方面 天然产物的生物合成是共同主题的变种。一起案件发生在 这一点就是莽草之路。从凝结开始 磷酸烯醇式丙酮酸与D-红素-4-磷酸结合，莽草酸途径有 一直是严密审查的焦点。 在地中海无枝霉中发现了莽草酸途径的一种变体 其中1-亚氨基-1-脱氧-D-红-4-磷酸取代D-红-4-磷酸 作为被命名为氨基莽草酸途径的可能起点。 假设3-氨基-3-脱氧-D-果糖6-磷酸是 将探索1-亚氨基-1-脱氧-D-红-4-磷酸。反过来， 阐述了3-氨基-3-脱氧-D-果糖6-磷酸的生物合成方法。 除了回答与来源相关的基本生物合成问题 关于氨基莽草酸途径所利用的氮原子，建议进行研究 最终可能导致一条生物催化路线，以获得适合的氨基莽草酸 用于合成抗流感药物。 莽草酸途径的第二个变体将在大肠杆菌中创建 其中，磷酸烯醇式丙酮酸将被丙酮酸取代为三碳 代谢物与D-红-4-磷酸缩合。这将需要 天然和进化的2-酮-3-脱氧-6-磷酸半乳糖酸醛缩酶的募集 催化丙酮酸与D-红-4-磷酸的缩合反应。 丙酮酸与莽草酸的缩合引发莽草酸途径 D-四氢叶酸-4-磷酸可显著提高玉米的产量 通过这种方式微生物合成的具有重要药用价值的分子 途径，并可用作莽草酸途径变体的范例 厌氧生长条件下的微生物。

DESCRIPTION (provided by applicant): Some of the more interesting aspects of natural product biosynthesis are the variations on common themes. A case in point is the shikimate pathway. Starting with the condensation of phosphoenolpyruvate with D-erythrose 4-phosphate, the shikimate pathway has been the focus of intense scrutiny. One variant of the shikimate pathway is found in Amycolatopsis mediterranei where 1-imino-1-deoxy-D-erythrose 4-phosphate replaces D-erythrose 4-phosphate as the likely starting point of what has been named the aminoshikimate pathway. The hypothesis that 3-amino-3-deoxy-D-fructose 6-phosphate is the source of 1-imino-1-deoxy-D-erythrose 4-phosphate will be explored. In turn, the biosynthesis of 3-amino-3-deoxy-D-fructose 6-phosphate is to be elaborated. Beyond answering fundamental biosynthetic questions associated with the source of the nitrogen atom utilized by the aminoshikimate pathway, proposed research could ultimately lead to a biocatalytic route to aminoshikimic acid suitable for use in the synthesis of anti-influenza agents. A second variant of the shikimate pathway is to be created in Escherichia coli where phosphoenolpyruvate will be replaced by pyruvate as the three-carbon metabolite condensed with D-erythrose 4-phosphate. This will require recruitment of native and evolved 2-keto-3-deoxy-6-phosphogalactonate aldolase to catalyze the condensation of pyruvate with D-erythrose 4-phosphate. Initiating the shikimate pathway with the condensation of pyruvate with D-erythrose 4-phosphate could substantially improve the yields of pharmaceutically important molecules microbially synthesized by way of this pathway and may serve as a paradigm of shikimate pathway variants employed by microbes under anaerobic growth conditions.