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August 16, 2026Bioprocess and Biosystems EngineeringOpen Access

Automated high-throughput screening combined with model-assisted analysis enables quantitative identification of process drivers and trade-offs during extracellular Fab production in Escherichia coli

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Authors

FSFabian Schröder-KleebergLKLucas KaspersetzSNSanchir Anar Neff

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Overview

High-throughput screening reveals trade-offs between productivity and cell lysis during Fab synthesis in Escherichia coli, indicating induction and temperature control bioprocess efficiency.

Key Points

  • To quantitatively evaluate the trade-offs between product formation, product release, and cellular robustness during extracellular Fab antibody fragment production in engineered Escherichia coli.
  • Screened 32 fed-batch cultivation conditions across six process parameters using 100 automated high-throughput bioreactor runs.
  • Utilized mechanistic modeling to quantify rates of cell lysis, product formation, and product release kinetics, including evaluations under large-scale substrate heterogeneity conditions.
  • Optimized conditions increased Fab titers approximately twofold to 730 mg/L and decreased cell lysis rates up to eightfold, accompanied by a 2.2-fold reduction in product release rate.
  • Induction strength was identified as the primary driver for maximizing Fab titer, whereas cultivation temperature regulated the balance between product release and cell lysis.
  • Moderate substrate heterogeneities simulating industrial scales enhanced Fab productivity while concurrently reducing cell lysis.

Cite This Study

Schröder-Kleeberg et al. (2026) studied this question.

synapsesocial.com/papers/6a8179abf2fb91fc834ace59https://doi.org/10.1007/s00449-026-03379-7
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