Shaping up a Mevalonate Pathway in the E. coli-E. coli Coculture System for the Production of Sesquiterpenes

Sesquiterpenoids are one of the most diverse families of natural compounds with various bioactivities and functions. The introduction of an exogenous mevalonate pathway was recognized to be the proficient approach in Escherichia coli for sesquiterpene biosynthesis. It is challenging from the coordination of the pathway constituents to forge an active mevalonate pathway, especially the balance of mevalonate generation and consumption by the top and bottom portions of the mevalonate pathway. In this study, the pathway constituents were categorized to hierarchically assemble an active mevalonate pathway, which was optimized in a Kronecker product fashion and evaluated with host adaptation. Finally, the E. coli-E. coli coculture system was created to minimize the mevalonate accumulation. As a result, these engineering processes significantly maximized pathway efficiency and improved sesquiterpene biosynthesis, which suggests an easy-to-use approach to erect E. coli cell factories for sesquiterpene production.