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

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.