A novel model-based control strategy for aerobic filamentous fungal fed-batch fermentation processes

Area of Science:

• Biotechnology
• Biochemical Engineering
• Process Control

Background:

• Filamentous fungal fed-batch fermentation is crucial for product manufacturing.
• Maximizing product yield requires optimizing both concentration and final biomass mass.
• Existing processes face challenges in achieving consistent final tank fill and avoiding oxygen limitations.

Purpose of the Study:

• To develop a novel model-based control strategy for filamentous fungal fed-batch fermentation.
• To maximize the total product achieved in a defined batch time by optimizing tank fill.
• To avoid oxygen-limited conditions during the fermentation process.

Main Methods:

• A two-stage approach involving off-line calculation of tank start fill and on-line control.
• Utilizing a mechanistic model, recursively updated with on-line measurements, to predict system states and future trajectories.
• Simulating system behavior to adjust feed rate based on oxygen transfer and mass trajectory.

Main Results:

• The control strategy achieved target fill within 5% of maximum fill in pilot-scale batches.
• Overfilling was successfully avoided, unlike in reference experiments.
• Variance in final tank fill was reduced by over 74%, demonstrating improved reproducibility.

Conclusions:

• The developed model-based control strategy effectively maximizes tank fill in filamentous fungal fed-batch processes.
• The strategy enhances process reproducibility and avoids overfilling, leading to more reliable biomanufacturing.
• Product concentration remained unaffected, indicating the control strategy's specific focus on optimizing fill and yield.