Optimal Bacterial Resource Allocation Strategies in Batch Processing

SIAM Journal on Applied Mathematics, Ahead of Print.
Abstract. The study of living microorganisms using resource allocation models has been key in elucidating natural behaviors of bacteria, by allowing allocation of microbial resources to be represented through optimal control strategies. The approach can also be applied to research in microbial cell factories, to investigate the optimal production of value-added compounds regulated by an external control. The latter is the subject of this paper, in which we study batch bioprocessing from a resource allocation perspective. Based on previous works, we propose a simple bacterial growth model accounting for the dynamics of the bioreactor and intracellular composition, and we analyze its asymptotic behavior and stability. Using optimization and optimal control theory, we study the production of biomass and metabolites of interest for infinite- and finite-time horizons. The resulting optimal control problems are studied using Pontryagin’s maximum principle and numerical methods, and the solutions found are characterized by the presence of the Fuller phenomenon (producing an infinite set of switching points occurring in a finite-time window) at the junctions with a second-order singular arc. The approach, inspired by biotechnological engineering, aims to shed light upon the role of cellular composition and resource allocation during batch processing and, at the same time, poses very interesting and challenging mathematical problems.