SBIR Phase I: Microbial production of paraxanthine, a caffeine replacement

SBIR 第一阶段：微生物生产副黄嘌呤（一种咖啡因替代品）

• 批准号: 2039060
• 负责人: Jeffrey Dietrich
• 金额: $ 25.6万
• 依托单位: REVEL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2039060&HistoricalAwards=false
• 关键词: SBIR; Phase; Microbial; production; paraxanthine

The broader impact of this Small Business Innovation (SBIR) Phase I project is the development of a biomanufacturing process to produce paraxanthine for use as a caffeine alternative in beverages and foods. For a large percentage of the population, caffeine is known to have negative side effects, including anxiety, jitteriness, and insomnia. In the case of anxiety, an estimated 40 million Americans suffer from an anxiety disorder, which may be exacerbated by caffeine in coffee, energy drinks, and other beverages. Paraxanthine is an active ingredient that has stimulatory qualities similar to caffeine but is less likely to cause anxiety and jitteriness. Thus, paraxanthine can play a role in contributing to improved mental health. The proposed project aims to develop a cost-efficient, biological method to manufacture paraxanthine. Producing paraxanthine at low cost is currently a significant technical challenge. The compound is only found naturally in substantial quantities within the human body as the result of caffeine metabolism; it is not produced in plants in above trace amounts. Furthermore, synthetic methods to produce paraxanthine are complex, inefficient, and expensive. The research goals of this Phase I project are to use a combination of protein and microbe engineering to develop a biological method to fermentatively produce paraxanthine at high yields and with high volumetric productivities. The approach uses directed evolution to select for enzymes and microbes with improved activity, enabling rapid iteration of the experimental design-build-test cycle. If successful, this technology will not only deliver an efficient paraxanthine production process, but it also establishes a novel, scalable platform that can be applied to improve upon other food ingredients, pharmaceuticals, and industrial chemicals.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.

这项小型企业创新（SBIR）I阶段项目的更广泛影响是开发生物制造过程，以生产黄牙蛋白，以用作饮料和食品中的咖啡因替代品。对于很大一部分人口，咖啡因众所周知，咖啡因具有负面影响，包括焦虑，抖动和失眠。在焦虑症的情况下，估计有4000万美国人患有焦虑症，咖啡因在咖啡，能量饮料和其他饮料中可能会加剧这种焦虑症。帕阳性蛋白是一种具有类似于咖啡因的刺激性的活性成分，但引起焦虑和抖动的可能性较小。因此，帕拉甘丁可以在改善心理健康方面发挥作用。拟议的项目旨在开发一种成本效益的生物学方法来生产paraxanthine。当前，以低成本生产Paraxanthine是一个重大的技术挑战。由于咖啡因代谢的结果，该化合物自然才在人体内部大量。它不是在上述痕量中产生的。此外，生产帕阳性蛋白的合成方法复杂，效率低下且昂贵。该阶段I项目的研究目标是结合蛋白质和微生物工程来开发一种生物学方法，以高产量和高体积生产率发酵生产帕阳性蛋白。该方法使用定向进化来选择具有改善活性的酶和微生物，从而可以快速迭代实验设计建筑测试周期。如果成功的话，这项技术不仅将提供有效的paraxanthine生产过程，而且还建立了一个新颖的可扩展平台，可用于改进其他食品成分，药品和工业化学化学。该奖项反映了NSF的法定任务，并通过基金会的知识优点和广泛的影响来评估NSF的法定任务。