STTR Phase I: Low-Cost, High-Purity Biobased Glucaric Acid

STTR 第一阶段：低成本、高纯度生物基葡萄糖酸

• 批准号: 1819514
• 负责人: Darcy Prather
• 金额: $ 22.5万
• 依托单位: Kalion, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1819514&HistoricalAwards=false
• 关键词: STTR; Phase; Low; Cost; Purity

The broader impact/commercial potential of this Small Business Technology Transfer(STTR) project is to develop a bio-based manufacturing process for glucaric acid and its intermediate, glucuronic acid. Microbial fermentation represents an attractive option for production of fuels and valuable chemicals from renewable resources, and glucaric acid can be produced from glucose, a renewable biomass-derived resource. The glucaric acid market was estimated at $550M in 2016, and has a plethora of uses ranging from detergents to food ingredients, corrosion inhibitors, and de-icing applications. The proposed project will engineer improved productivity of the microbe using C5/C6 sugars, thus accelerating the production of low-cost, high-purity glucaric acid. Achieving these bioprocess improvements will facilitate widespread adoption of bio-based glucaric acid in a variety of markets, broadening opportunity for US products. These applications include coatings, foams and foaming aids, electrolytes, gels, polymers, and polymer additives.This STTR Phase I project proposes to perform multi-omics studies to characterize the physiology of E. coli strains producing glucaric acid via fermentation, and develop strain engineering strategies to enable high yield and productivity. Most fermentation products are highly reduced compared to the starting sugar, and care must be taken to maintain cells in a reduced state, meaning high NADH/NAD ratio, to drive the NADH-consuming biosynthetic reactions. Products that are derived from sugar oxidation, in contrast, pose a much different challenge, and have been explored to a much lesser extent. Here, additional oxygen is needed to accept the excess electrons generated during glucose oxidation. It is well known that both S. cerevisiae and E. coli, two of the most common organisms for industrial application, are limited in their electron transport chain capacity, resulting in overflow products from high glucose uptake rates. Regardless of the oxygen transfer ability of the fermentation equipment, there is an inherent maximum production rate of these organisms. In this project, the plan is to develop E. coli strains with increased respiration capacity, thus increasing the maximum glucose oxidation rate. Glucaric acid, which can be produced from glucose via 3 enzymatic reaction steps, is an exemplary product.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该小企业技术转让（STTR）项目的更广泛影响/商业潜力是开发葡萄糖二酸及其中间体葡萄糖醛酸的生物基制造工艺。微生物发酵代表了从可再生资源生产燃料和有价值的化学品的有吸引力的选择，并且葡糖二酸可以从葡萄糖（一种可再生的生物质衍生资源）生产。 2016年，葡糖二酸市场估计为5.5亿美元，用途广泛，从洗涤剂到食品配料、缓蚀剂和除冰应用。 拟议的项目将利用C5/C6糖提高微生物的生产力，从而加快低成本、高纯度葡萄糖二酸的生产。实现这些生物工艺改进将促进生物基葡糖二酸在各种市场的广泛采用，为美国产品拓宽机会。这些应用包括涂料、泡沫和发泡助剂、电解质、凝胶、聚合物和聚合物添加剂。大肠杆菌菌株通过发酵生产葡糖二酸，并开发菌株工程策略，以实现高产率和生产力。与起始糖相比，大多数发酵产物高度还原，必须注意保持细胞处于还原状态，这意味着高NADH/NAD比率，以驱动消耗NADH的生物合成反应。相比之下，来自糖氧化的产品构成了一个非常不同的挑战，并且已经在很小程度上进行了探索。在这里，需要额外的氧来接受葡萄糖氧化过程中产生的过量电子。众所周知，S. cerevisiae和E.大肠杆菌是工业应用中最常见的两种生物体，其电子传递链能力有限，导致高葡萄糖摄取速率产生溢出产物。不管发酵设备的氧传递能力如何，这些生物体都存在固有的最大生产速率。本项目计划开发E.大肠杆菌菌株具有增加的呼吸能力，从而增加最大葡萄糖氧化速率。葡萄糖二酸是一个典型的产品，它可以通过3个酶促反应步骤从葡萄糖中产生。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。