Metabolic Reaction Network-Based Model Predictive Control of Bioprocesses

Abstract

Bioprocesses are increasingly used for the production of high added value products. Microorganisms are used in bioprocesses to mediate or catalyze the necessary reactions. This makes bioprocesses highly nonlinear and the governing mechanisms are complex. These complex governing mechanisms can be modeled by a metabolic network that comprises all interactions within the cells of the microbial population present in the bioprocess. The current state of the art in bioprocess control is model predictive control based on the use of macroscopic models, solely accounting for substrate, biomass, and product mass balances. These macroscopic models do not account for the underlying mechanisms governing the observed process behavior. Consequently, opportunities are missed to fully exploit the available process knowledge to operate the process in a more sustainable manner. In this article, a procedure is presented for metabolic network-based model predictive control. This procedure uses a combined moving horizon-model predictive control strategy to monitor the flux state and optimize the bioprocess under study. A CSTR bioreactor model has been combined with a small-scale metabolic network to illustrate the performance of the presented procedure.

Precision fermentation with mass spectrometry‐based spent media analysis

“…The macroscopic models used in contemporary online bioprocess control barely use the full scope of intracellular mechanisms. An example of a state‐of‐the‐art process control was demonstrated by using moving horizon estimation on a combination of a Continuous stirred tank reactor (CSTR) and a simple metabolic network (Nimmegeers et al, 2021). When coupled with actual metabolomic data, such studies can be the future of model predictive control in bioprocess development via soft sensors.…”