Optimal control of bacterial growth for metabolite production: The role of timing and costs of control

The growth of microorganisms is controlled by strategies for the dynamical allocation of available resources over different cellular functions. Synthetic biology approaches are considered nowadays to artificially modify these strategies and turn microbial populations into biotechnological factories for the production of metabolites of interest. In our recent work [1], [2] we have studied dynamics of microbial resource allocation and growth in terms of coarse-grained self-replicator models described by ordinary differential equations, and proposed artificial control strategies for the optimization of metabolite production based on the reengineering of resource allocation. In this paper, we elaborate on our earlier results and further investigate synthetic resource allocation control strategies. Using numerical simulation, we study the effect on growth and bioproduction of the (biological or technological) costs associated with discontinuous control strategies, and of the time allotted to optimal substrate utilization. Results provide novel insight into the most favorable synthetic control strategies.