Shikimate Pathway Variants

莽草通路变异体

• 批准号: 6465605
• 负责人: JOHN W FROST
• 金额: $ 28.23万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465605
• 关键词: Bacteroides; Escherichia coli; antiviral agents; biological products; directed evolution; drug design /synthesis /production; enzyme substrate; fructose phosphate; genetic manipulation; gram negative bacteria; mass spectrometry; peptide chemical synthesis; pyruvates; shikimate

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.

描述（由申请人提供）：一些更有趣的方面