SBIR Phase II: Microbial Stem Cell Technology for High-Yield Terpene Biomanufacturing

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project will be to develop improved biomanufacturing techniques that reduce costs and enhance yields. This microbial stem cell technology is a platform expected to significantly increase bioreactor productivity, bringing transformative advancements to multiple markets. The first target market, flavors and fragrances, find application in several industries such as beverages, savory and snacks, dairy products, bakery, confectionery, consumer products, and fine fragrances. This market is estimated to be $30.9B in 2024 and is projected to reach $50.7B by 2033, growing at a compound annual growth rate (CAGR) of 4.82%. Widespread implementation of this platform across diverse industrial segments would strengthen supply chain resilience and boost US economic competitiveness. Additionally, it would create opportunities for workforce development, offer unique training programs for students, and significantly contribute to establishing a skilled biotech workforce in Wyoming and the High Plains region. The proposed project provides a solution to the common problem of product cytotoxicity in microbial biofermentations. Microbial biofermentation has generated serious interest among industrial producers of flavors and fragrances for efficient biofermentative methods for making their products, yet they are deterred by the limitations of conventional biomanufacturing. The proposed project intends to overcome these limitations and capture growing market opportunities by providing a new genetic technology that enables substantially higher biofermentation yields. The SBIR Phase II program will support the following R&D tasks on the road toward de-risking and commercialization: (a) validation in bench-top bioreactors; (b) expansion of the terpenoid product portfolio, and (c) scale-up to 300L production. The validation will include conducting high cell density fermentation trials, measuring production rates, titers, and other critical fermentation metrics. This will be followed by designing new strains to expand the terpenoid portfolio and scale up terpenoid production. By the end of this project, the technology should be ready for the successful operation in industrial bioreactors with consistent product quality and yield. Since this is a platform technology that could be applied to a wide range of biofermentation products, expanding the potential impact in the biomanufacturing industry. 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.