SBIR Phase I: Engineering Microbial Biosynthesis of a Non-caloric Natural Sweetener

这个小企业创新研究（SBIR）第一阶段项目将解决合成生物学和代谢工程技术的潜力，以产生过量生产无热量天然甜味剂的微生物菌株。目前天然甜味剂的生产和利用受到天然植物种植和生产成本高的限制。因此，尽管天然甜味剂已经使用了数千年，并且以其健康和无热量的特性而闻名，但它们的高生产成本使它们无法与广泛用于饮料和碳酸软饮料的合成甜味剂直接竞争。我们的目标是开发一种用于生物合成生产的发酵工艺，使消费者市场更多地采用低热量的天然甜味剂。代谢工程方法将用于将天然生物合成途径从植物转移到细菌宿主，并在商业上可行的水平上优化代谢通量以实现过剩生产。我们预计将获得一种高生产率菌株，适合继续商业化努力。总的来说，该项目如果成功，将为无热量天然甜味剂的可持续生产提供一条新的途径。该项目的更广泛的影响/商业潜力是开发一种微生物工艺，用于经济和可持续地生产无热量天然甜味剂，具有30亿美元的潜在全球市场。这种甜味剂的使用将改善口味，并扩大对低热量饮料、糖果、烘焙食品、乳制品等的采用，从而通过减少糖尿病和其他与肥胖有关的疾病的发病率而有益于公众健康。这些好处将转化为美国和全球医疗成本的降低。此外，这项研究将开发可推广的合成生物学技术，用于大量生产对人类健康和保健有许多应用的天然产品。

This Small Business Innovation Research (SBIR) Phase I project will address the potential of synthetic biology and metabolic engineering technologies to generate microbial strains over-producing a non-caloric natural sweetener. Current production and utilization of natural sweeteners is limited due to the high cost of the cultivation and production from native plant sources. So, although natural sweeteners have been used for thousands of years, and are known for their healthy and non-caloric properties, their high production cost prevents them from directly competing with synthetic sweeteners extensively used in beverages and carbonated soft drinks. Our objective is to develop a fermentation process for biosynthetic production allowing increased adoption of low-calorie, natural sweeteners in consumer markets. Metabolic engineering approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and optimize the metabolic flux for the overproduction at a commercially viable level. We anticipate that a high-productivity strain will be obtained, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route to the non-caloric natural sweeteners.The broader impact/commercial potential of this project is the development of a microbial process for the economical and sustainable production of non-caloric natural sweetener, with a potential $3 billion global market. The use of this sweetener will improve taste profiles and expand adoption of low-calorie beverages, confectionaries, baked goods, dairy products, and so on, thus benefitting public health by reducing incidence of diabetes and other obesity-related diseases. Such benefits will translate to reduced healthcare cost both in the U.S. and globally. Additionally, this research will develop generalizable synthetic biology techniques for the high-volume production of natural products with many applications for human health and wellness.