(759b) Biosensor-Guided Improvement of Microbial Alkaloid Production

Monoterpene indole alkaloids (MIAs) have important therapeutic value, including as anticancer and antimalarial agents. Because of their chemical complexity, therapeutic MIAs, or advanced intermediates thereof, are often isolated from the native plants. Here, I present our recent work in the microbial production of the modified MIA 10-hydroxystrictosidine from glucose and the monoterpene secologanin via a pterin-dependent mono-oxidation strategy. This work opens the door to the scalable production of alkaloids as well as the production of modified MIAs to serve as late intermediates in the semisynthesis of known and novel therapeutics. In order to reach scalable levels, we are currently focusing on creating G-protein coupled receptor (GPCR)-based biosensors to increase microbial production of biogenic amines. This will allow for high-throughput development of higher yielding alkaloid production strains and serve as an example of the utility of GPCR-based biosensors in the development of more productive chemical-producing microbial platforms.