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Main Title: A model‐based framework for parallel scale‐down fed‐batch cultivations in mini‐bioreactors for accelerated phenotyping
Author(s): Anane, Emmanuel
García, Ángel Córcoles
Haby, Benjamin
Hans, Sebastian
Krausch, Niels
Krewinkel, Manuel
Hauptmann, Peter
Neubauer, Peter
Cruz-Bournazou, Mariano Nicolas
Type: Article
Language Code: en
Abstract: Concentration gradients that occur in large industrial‐scale bioreactors due to mass transfer limitations have significant effects on process efficiency. Hence, it is desirable to investigate the response of strains to such heterogeneities to reduce the risk of failure during process scale‐up. Although there are various scale‐down techniques to study these effects, scale‐down strategies are rarely applied in the early developmental phases of a bioprocess, as they have not yet been implemented on small‐scale parallel cultivation devices. In this study, we combine mechanistic growth models with a parallel mini‐bioreactor system to create a high‐throughput platform for studying the response of Escherichia coli strains to concentration gradients. As a scaled‐down approach, a model‐based glucose pulse feeding scheme is applied and compared with a continuous feed profile to study the influence of glucose and dissolved oxygen gradients on both cell physiology and incorporation of noncanonical amino acids into recombinant proinsulin. The results show a significant increase in the incorporation of the noncanonical amino acid norvaline in the soluble intracellular extract and in the recombinant product in cultures with glucose/oxygen oscillations. Interestingly, the amount of norvaline depends on the pulse frequency and is negligible with continuous feeding, confirming observations from large‐scale cultivations. Most importantly, the results also show that a larger number of the model parameters are significantly affected by the scale‐down scheme, compared with the reference cultivations. In this example, it was possible to describe the effects of oscillations in a single parallel experiment. The platform offers the opportunity to combine strain screening with scale‐down studies to select the most robust strains for bioprocess scale‐up.
Issue Date: 30-Jul-2019
Date Available: 13-Feb-2020
DDC Class: 570 Biowissenschaften; Biologie
Subject(s): Escherichia coli
scale‐up effects
Sponsor/Funder: EC/H2020/643056/EU/Rapid Bioprocess Development/Biorapid
TU Berlin, Open-Access-Mittel - 2019
Journal Title: Biotechnology and Bioengineering
Publisher: Wiley
Publisher Place: New York, NY
Volume: 116
Issue: 11
Publisher DOI: 10.1002/bit.27116
Page Start: 2906
Page End: 2918
EISSN: 1097-0290
ISSN: 0006-3592
Appears in Collections:FG Bioverfahrenstechnik » Publications

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