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Physiological capacities decline during induced bioprocesses leading to substrate accumulation
Wieland N Reichelt1, Markus Brillmann1, Peter Thurrold2
1Christian Doppler Laboratory for Mechanistic and Physiological Methods for Improved Bioprocesses, Institute of Chemical Engineering, Vienna University of Technology, Vienna, Austria.
Biotechnology Journal
|January 26, 2017
Summary
Substrate accumulation in E. coli cultivation is dynamic, not static. Understanding the critical substrate uptake rate (qScrit) and its real-time changes is key to preventing batch failures and improving scale-up.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Process Engineering
Background:
- Substrate accumulation during E. coli cultivation for recombinant protein production complicates scale-up and can lead to batch failures.
- This accumulation is linked to exceeding the critical substrate uptake rate (qScrit), often treated as a static parameter.
Purpose of the Study:
- To investigate the dynamic nature of the critical substrate uptake rate (qScrit) during E. coli induction phase.
- To develop a predictive model for qScrit and explore strategies to prevent substrate accumulation.
Main Methods:
- Utilized substrate pulse experiments for physiological strain characterization.
- Quantified qScrit under varying temperature and time conditions.
- Conducted physiologically controlled experiments with oscillating substrate set points.
Main Results:
- Demonstrated that qScrit is temperature and time-dependent, challenging the static model.
- Observed substrate accumulation even when the predicted qScrit boundary was not exceeded.
- Identified a significant interrelation between metabolic activity and the timely decline of qScrit.
Conclusions:
- qScrit exhibits dynamic behavior, necessitating comprehensive strain characterization or real-time physiological feedback control.
- Effective monitoring of dynamic qScrit is crucial for preventing substrate accumulation and ensuring robust bioprocesses.
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