STTR Phase I: Overcoming Metabolic Pathway Limitations through De Novo Pathway Design for Terpenoid Biosynthesis

This Small Business Innovation Research (STTR) Phase I project aims to develop a novel, high flux terpenoid precursor pathway by circumventing limitations of the bacterial methyl erythritol-phosphate (MEP) pathway for the renewable production of monoterpenoids. Monoterpenoids are natural chemical precursors for several consumer products, and many are produced via highly polluting chemical processes. In the proposed project the plan is to sidestep some of the MEP pathway limitations by designing de novo metabolic pathways. The designed/predicted enzymes will be characterized individually and assembled into a pathway. Further, multivariate-modular metabolic engineering (MMME) approaches will be used to assemble the upstream and downstream pathways to optimize the metabolic flux for the overproduction at commercially viable levels. The broader impact/commercial potential of this project, if successful, will be to develop a microbial monoterpenoid production platform from renewable sugars that will retain and develop sustainable manufacturing of monoterpenoid-derived products in the US. By this strategy, terpenoids can be made at much higher productivities than the native bacterial MEP pathway. While the immediate focus is on the $1B+ monoterpene/derivative market, this approach will benefit US manufacturing of all terpenoids, in total a $5B+ market. Overall, this project will provide a new sustainable production route for these natural chemicals.