Multi-input dynamic pathway regulation for optimized microbial production

Given the depletion of fossil resources and environmental concerns,
we are transitioning toward a bio-based economy in which microbes
are considered as the chemical factories of the future. Microbial
hosts are engineered to have metabolic properties for the production
of target chemicals, but often productivities are too low for economic
viability.

This can be explained by the cellular stress experienced by
engineered microbial cells due to an interplay of the heterologous
production pathway with cellular physiology. Here, I will investigate
the engineering design and principles of multi-input dynamic pathway
control on a production pathway that functions robustly, leading to
higher productivities. Specific objectives entail (i) the mathematical
modelling in which reaction kinetics and regulation dynamics are
combined, (ii) the development of a biosensor toolbox harboring
engineered transcription factors and (iii) their use for the engineering
of pathway regulation based on model predictions. As a proof-ofconcept, this engineering will be performed for 3-hydroxypropionic acid production pathway in the model bacterium Escherichia coli, with 3-hydroxypropionic acid being a valuable platform chemical for a wide variety of applications.

This project will advance the state-of-theart of dynamic pathway control for a variety of hosts and products, and will lead to higher microbial productivities.