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Microbial cell factories offer sustainable chemical production but struggle with industrial scale-up due to a lack of robustness. This review explores methods to enhance cell factory stability and performance under industrial conditions.

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Synthetic Biology

Background:

  • Microbial cell factories are crucial for sustainable chemical synthesis.
  • Metabolic engineering advances cell factories but industrial scale-up reveals limitations in yield, titer, and productivity.
  • A key limitation is the lack of robustness, defined as maintaining a stable phenotype under process perturbations.

Purpose of the Study:

  • To review industrial perturbations affecting microbial cell factories.
  • To discuss technologies for countering process variability and enhancing robustness.
  • To differentiate robustness from tolerance and explore single-cell studies for improvement.

Main Methods:

  • Review of literature on industrial perturbations (predictable and stochastic).
  • Analysis of state-of-the-art technologies for process variability mitigation.
  • Discussion of single-cell analysis techniques for robustness assessment.

Main Results:

  • Identified predictable and stochastic perturbations in industrial bioprocesses.
  • Highlighted technologies to counter process variability and improve robustness.
  • Differentiated robustness from tolerance, emphasizing the former's importance for industrial application.

Conclusions:

  • Robustness is critical for the long-term industrial viability of microbial cell factories.
  • Single-cell studies offer potential for enhancing system robustness.
  • Standardized quantification of robustness is needed to guide strain selection for bioprocesses.