SBIR Phase II: Biological production of paraxanthine, a caffeine replacement

The broader impact of this Small Business Innovation (SBIR) Phase II 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 negative effects on sleep quality. In the case of anxiety, an estimated 40MM Americans suffer from an anxiety disorder, and the consumption of caffeine in coffee, energy drinks, and other beverages is known to exacerbate stress. Paraxanthine is an active metabolite of caffeine that has similar stimulatory qualities but with potentially fewer side effects. Additionally, paraxanthine has a shorter half-life (i.e., it is cleared from the body faster) as compared to caffeine. Thus, paraxanthine may play a role in contributing to improved sleep quality and mental wellness. 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 and relatively expensive. The research goals of this Phase II project are to develop and optimize a process using an engineering enzyme to fermentatively produce paraxanthine at high yields and with high volumetric productivities. The approach seeks to employ real-time bioreactor monitoring, 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.