NMPC-Based Workflow for Simultaneous Process and Model Development Applied to a Fed-Batch Process for Recombinant C. glutamicum

Philipp Levermann,Henning Zaun,Jürgen Kuballa,Karl Michael Schoop,Johannes Möller,Fabian Freiberger,Ralf Pörtner,Volker C Hass,Uma Katha

doi:10.3390/pr8101313

Abstract

For the fast and improved development of bioprocesses, new strategies are required where both strain and process development are performed in parallel. Here, a workflow based on a Nonlinear Model Predictive Control (NMPC) algorithm is described for the model-assisted development of biotechnological processes. By using the NMPC algorithm, the process is designed with respect to a target function (product yield, biomass concentration) with a drastically decreased number of experiments. A workflow for the usage of the NMPC algorithm as a process development tool is outlined. The NMPC algorithm is capable of improving various process states, such as product yield and biomass concentration. It uses on-line and at-line data and controls and optimizes the process by model-based process extrapolation. In this study, the algorithm is applied to a Corynebacterium glutamicum process. In conclusion, the potency of the NMPC algorithm as a powerful tool for process development is demonstrated. In particular, the benefits of the system regarding the characterization and optimization of a fed-batch process are outlined. With the NMPC algorithm, process development can be run simultaneously to strain development, resulting in a shortened time to market for novel products.

Highlights

The development of bioprocesses can be time-consuming and cost-intensive
This way, in addition to the Hamburg, Germany) with the implemented Nonlinear Model Predictive Control (NMPC) algorithm was established. This way, in addition commonly used control the bioreactor (controls for stirrer speed, pH-value, temperature, to the commonly used system controlfor system for the bioreactor, the model system for the process extrapolation and optimization is realized in therealized control temperature, etc.), the model system for the process extrapolation and optimization is software
First the results of the initial experiments and thereafter the NMPC-controlled fed-batches are shown to illustrate the development of the C. glutamicum process

Summary

Introduction

The development of bioprocesses can be time-consuming and cost-intensive. After the selection of a promising production strain, the actual process development for the production of large quantities of the target molecule starts. By this step-by-step approach, usually a lot of time is wasted. To reduce this effort, different approaches such as, for example, Design of Experiment (DoE) are used which offer a systematic method for the evaluation of multiple process variables, but still require a large number of experiments [1,2,3].

Methods

Results

Conclusion