External control of microbial populations for bioproduction: A modeling and optimization viewpoint

When engineering microbes for bioproduction, one is necessarily confronted with the existing tradeoff between efficient bioproduction and maintenance of the cell physiology and growth. Moreover, because cellular processes at the single-cell level are coupled with population dynamics via selection mechanisms, this question should be investigated at the population level. Identifying the temporal induction profile that maximizes production in the long term is highly challenging. External control allows to dynamically adapt the strength of the induction from the outside based on intracellular readouts. It allows benchmarking various regulation functions and, coupled with modeling approaches, identifying and applying optimal strategies. In this review, we describe recent advances using quantitative approaches, modeling, and control theory that pave the way to compute external stimulations maximizing long-term production.