PECASE: Bioengineering of Secondary Metabolic Pathways

PECASE：次级代谢途径的生物工程

• 批准号: 0545860
• 负责人: Yi Tang
• 金额: $ 40万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0545860&HistoricalAwards=false
• 关键词: PECASE; Bioengineering; Secondary; Metabolic; Pathways

Tang0545860Tetracyclines have been prescribed as broad-spectrum antibiotics and have recently been used in anticancer therapies. The objective of this research is to understand the metabolic pathway, the molecular assembly, and the combinatorial potential of tetracycline biosynthesis. Four specific aims will be pursued: (1) Reconstitute and understand the assembly of the amidated tetracycline backbone; (2) Reconstitute the first tetracyclic intermediate in oxytetracycline (oxy) pathway and use metabolic engineering to produce a novel C8-hydroxylated analog of the intermediate; (3) Reconstitute the tailoring steps in oxy pathway and construct a series of strains that can produce valuable metabolic intermediates; (4) Engineered biosynthesis of novel glycosylated analogs of tetracycline through shuffling of heterologous secondary metabolic pathways. The research and education efforts will be integrated through the following mechanisms: 1) Two recently developed, core biotechnology courses will be enriched to increase critical thinking and active learning by the students; 2) Community outreach will be emphasized by inviting underprivileged minority students in the greater Los Angeles metropolitan area to learn research during the summer months, as well as participating in university-community events to promote science education and life-long learning.

Tang0545860Tetracyclines已被处方为广谱抗生素，最近用于抗癌疗法。 这项研究的目的是了解四环素生物合成的代谢途径，分子组装和组合潜力。 将追求四个具体目标：（1）重新构建并了解胺化四环素骨干的组装； （2）重建Oxytacycline（Oxy）途径中的第一个四环素中间体，并使用代谢工程生产中间体的新型C8羟基化类似物； （3）重建氧气途径的裁缝步骤，并构建一系列可以产生有价值的代谢中间体的菌株； （4）四环素的新型糖基化类似物的工程生物合成通过异源次级代谢途径进行改组。 研究和教育工作将通过以下机制进行整合：1）两个最近开发的，核心生物技术课程将得到丰富，以增加学生的批判性思维和积极学习； 2）将通过邀请大洛杉矶大都会地区的贫困少数族裔学生在夏季学习研究，并参加大学社区活动以促进科学教育和终身学习。