Overriding Bioprocess Perturbations With a Cell-Machine Interface for Reliable Microbial Stress-Response Control

Area of Science:

• Systems and Synthetic Biology
• Biotechnology
• Microbial Engineering

Background:

• Controlling cell population dynamics and phenotypic diversification is crucial for engineered gene circuits.
• Industrial bioreactor conditions often involve environmental perturbations that impact cell behavior.
• Existing cell-machine interfaces underexplored in the context of industrial bioreactor perturbations.

Purpose of the Study:

• Investigate the impact of industrial bioreactor perturbations on the general stress response in Escherichia coli and Saccharomyces cerevisiae.
• Evaluate the performance of the Segregostat real-time control system under these conditions.

Main Methods:

• Scale-down bioreactor experiments.
• Utilized the Segregostat system with automated flow cytometry for dynamic nutrient shifts.
• Assessed stress response control under severe perturbations like extended residence times.

Main Results:

• The Segregostat system demonstrated robust control of stress response.
• Effective control was maintained even under severe bioreactor perturbations.
• Hypothesized robustness stems from amplifying host-compatible fluctuations.

Conclusions:

• Environmental factors must be integrated into control strategies for reliable gene circuit behavior.
• The Segregostat system shows promise for industrial bioprocessing.
• Ensuring uniform responses from engineered gene circuits in industrial settings is achievable.