SBIR Phase I: Engineering Bacteria for Low Cost Renewable Biochemical Production

这个小企业创新研究第一阶段项目将开发一种定制设计的微生物生物催化剂，用于高价值萜类生物化学物质的可再生生产。从精油中提取的萜类生物化学物质被用于许多消费品和食品添加剂。它们中的许多以各种立体异构体形式在自然界中积累，每一种都具有独特的性质和应用。这些分子被认为主要在生态作用中起作用，作为食草动物摄食的威慑，抗真菌防御和传粉者的引诱剂。研究目标是开发一种生物合成生产的发酵工艺，允许更多地采用这种天然替代品来代替合成化学品。多变量模块化代谢工程（MMME）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。预计将有一种高生产率菌株，适合继续商业化努力。总的来说，这个项目如果成功，将为这些天然化学品提供一条新的可持续生产路线。该项目的更广泛的影响/商业潜力是开发一种微生物工艺，以经济和可持续地生产高价值萜类生物化学品。这些萜类生物化学物质在各种行业中都有应用，包括农用化学品、石油化工、风味和香料（F&amp；F）化学品；具体来说，它们通常被用作调味剂、生物除草剂、发芽抑制剂和生物害虫驱避剂。总的来说，潜在的潜在市场超过30亿美元。微生物生产将通过提高生产过程的可再生性和将生产从海外转移到美国来造福社会。总之，能够生产目标的微生物的发展将使目标的可持续生产成为可能，并在美国创造就业机会。本研究将通过可持续的生产过程，为天然产品的大批量生产开发可推广的微生物菌株工程技术。

This Small Business Innovation Research Phase I project will develop a custom-designed microbial biocatalyst for the renewable production of high value terpenoid biochemicals. Terpenoid biochemicals derived from essential oils are used in numerous consumer products and as food additives. Many of them accumulate in nature in various stereo-isomeric forms, each of which possesses unique properties and applications. These molecules are believed to function principally in ecological roles, serving as herbivore-feeding deterrents, antifungal defenses, and pollinator attractants. The research objective is to develop a fermentation process for biosynthetic production allowing increased adoption of such natural alternatives to synthetic chemicals. Multivariate-Modular Metabolic engineering (MMME) approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and to optimize the metabolic flux for the overproduction at a commercially viable level. A high-productivity strain is anticipated, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route for these natural chemicals.The broader impact/commercial potential of this project is the development of a microbial process for the economic and sustainable production of high value terpenoid biochemicals. These terpenoid biochemicals have applications in a variety of industries ranging from agro-chemicals, petro-chemicals and flavor and fragrance (F&F) chemicals; specifically they are commonly used as flavor agents, bio- herbicides, sprout inhibitors and as bio-pest repellents. In all, the total potential addressable markets exceed $3 Billion. Microbial production will benefit society by improving the renewability of the production process and by relocating production from overseas to the US. In summary, the development of microbes capable of producing the target will enable sustainable production of the target as well as create jobs in the US. This research will develop generalizable microbial strain engineering techniques for the high-volume production of natural products through a sustainable manufacturing process.