SBIR Phase I:Metabolic Engineering of Isoflavonoid Biosynthesis in Eschericia coli

SBIR第一期：大肠杆菌异黄酮生物合成的代谢工程

• 批准号: 0712324
• 负责人: John Daiss
• 金额: --
• 依托单位: First Wave Technologies, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0712324&HistoricalAwards=false
• 关键词: SBIR; Phase; Metabolic; Engineering; Isoflavonoid

This Small Business Innovation Research Phase I research will create a biosynthetic system for economical, environmentally benign, versatile production of isoflavonoids, natural and non-natural. By transferring the optimal enzymes for the synthesis of isoflavonoids from plants into E. coli, the research will create self-replicating metabolic machines that convert inexpensive feedstocks into any of a diverse array of isoflavonoids determined by the precursors used and the enzymes added. Specifically, the research will co-develop the key enzymes in the biosynthesis of isoflavonoids and an E. coli strain adapted for the particular needs of these enzymes. This will provide a scaffold upon which other enzymes can be added to simultaneously create new isoflavonoids and the means of their production. Isoflavonoids are natural compounds from legumes that have great potential for improving human health. The simplest isoflavonoids , genistein and daidzein, have attracted clinical attention for their antioxidant and anticancer activities. More complex isoflavonoids such as puerarin and formononetin are also being evaluated for nutraceutical or pharmaceutical applications. Attracted by the numerous ways that isoflavonoids alter human cellular processes, chemists have begun to synthesize new generations of non-natural, isoflavonoid-based pharmaceutical candidates that might be more effective and specific than their natural precursors. In fact, some are already in clinical trials. The supply of isoflavonoids is based on extraction from plants, a process that is neither efficient nor consistent, and chemical synthesis which is excellent for some molecules but inefficient for others such as those that contains sugars or alkyl groups at specific positions on the isoflavonoid core structure. This process will expand the availability of these compounds and provide novel products for the benefit of the country.

这个小企业创新研究第一阶段的研究将创建一个生物合成系统，用于经济，环境友好，多功能的天然和非天然的生物合成产品。 通过将植物中最适合合成甘草酸的酶转入E.该研究将创造自我复制的代谢机器，将廉价的原料转化为由所使用的前体和添加的酶决定的多种多样的代谢物中的任何一种。 具体而言，该研究将共同开发生物合成中的关键酶和一种E。大肠杆菌菌株适应这些酶的特殊需要。 这将提供一个支架，在其上可以添加其他酶，以同时产生新的酶及其生产手段。 异黄酮是来自豆类的天然化合物，具有改善人类健康的巨大潜力。 最简单的黄酮类化合物染料木黄酮和大豆苷元因其抗氧化和抗癌活性而引起临床关注。 更复杂的化合物，如葛根素和芒柄花素也正在评估营养或药物应用。 由于类黄酮改变人类细胞过程的多种方式，化学家们已经开始合成新一代的非天然的、基于类黄酮的候选药物，这些药物可能比它们的天然前体更有效、更特异。 事实上，有些已经在临床试验中。维生素B1的供应是基于从植物中提取，这是一种既不高效也不一致的过程，以及化学合成，这对某些分子来说是极好的，但对其他分子来说是低效的，例如在维生素B1核心结构上的特定位置含有糖或烷基的那些分子。这一过程将扩大这些化合物的供应，并为国家提供新产品。