Huadong Peng

Project title: Biosensor-assisted screening and modular coculture setup for fermentation-based manufacturing of aromatics

Host Institution: Technical University of Denmark (DTU)

Host Supervisor: Dr. Michael Krogh Jensen

Co-host Institution: Eindhoven University of Technology (TU/e)

Co-host Supervisor: Prof. dr. Peter A.J. Hilbers

Summary project: Aromatics have a wide range of applications in food, pharmaceutical and chemical industries. Nowadays, the production of aromatics is mainly from petroleum-derived chemical process or extraction from plant resources. Microbial-derived aromatics provides an alternative renewable approach, which could be engineered, easily scalable and standardised. However, the development of aromatics-producing microbial cell factories is limited by the time-consuming design-build-test-learn (DBTL) cycle, and the often complex and very long aromatics synthesis pathways. This proposal aims to demonstrate the synergy of cutting-edge synthetic biology tools of genetically encoded biosensors and modular coculture ecosystem for improved bioproduction of high-value aromatic neurotransmitter melatonin and the psychoactive monoterpene indole alkaloid alstonine, currently sourced by chemical and plant-based extraction processes, respectively. Here, melatonin and alstonine biosynthetic pathways will be split via division of labor into advanced “sender” and “receiver” yeast strains. Strains will be constructed based on available high-tryptophan yeast producers and equipped with GPCR biosensors to allow either one-way or two-way communications between sender and receiver monocultures. Mathematical models and precursor feeding tests will help identify metabolic rate-limits, and GPCR biosensors will be deployed for dynamic regulation within cocultures. This proposal will be the first time to improve aromatics production by combining the advantages from multiple disciplines including the latest synthetic biology tools, emerging microbial consortia, and mathematical modelling of coculture behaviour. The impact of the proposal will be novel coculture-based supply chains for marketed aromatics as well as a predictive model for development of advanced coculture modalities.