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Main Title: Modelling concentration gradients in fed‐batch cultivations of E. coli – towards the flexible design of scale‐down experiments
Author(s): Anane, Emmanuel
Sawatzki, Annina
Neubauer, Peter
Cruz-Bournazou, Mariano Nicolas
Type: Article
Language Code: en
Abstract: BACKGROUND: The impact of concentration gradients in large industrial-scale bioreactors on microbial physiology can be studied in scale-down bioreactors. However, scale-down systems pose several challenges in construction, operation and footprint. Therefore, it is challenging to implement them in emerging technologies for bioprocess development, such as in high throughput cultivation platforms. In this study, a mechanistic model of a two-compartment scale-down bioreactor is developed. Simulations from this model are then used as bases for a pulse-based scale-down bioreactor suitable for application in parallel cultivation systems. RESULTS: As an application, the pulse-based system model was used to study the misincorporation of non-canonical branched-chain amino acids into recombinant pre-proinsulin expressed in Escherichia coli, as a response to oscillations in glucose and dissolved oxygen concentrations. The results show significant accumulation of overflow metabolites, up to 18.3 % loss in product yield and up to 10 fold accumulation of the non-canonical amino acids norvaline and norleucine in the product in the pulse-based cultivation, compared to a reference cultivation. CONCLUSIONS: Our results indicate that the combination of a pulse-based scale-down approach with mechanistic models is a very suitable method to test strain robustness and physiological constraints at the early stages of bioprocess development.
Issue Date: 13-Aug-2018
Date Available: 15-Nov-2019
DDC Class: 660 Chemische Verfahrenstechnik
Subject(s): E. coli
glucose gradients
oxygen gradients
inclusion bodies
Sponsor/Funder: EC/H2020/643056/EU/Rapid Bioprocess Development/Biorapid
Journal Title: Journal of chemical technology & biotechnology
Publisher: Wiley
Publisher Place: Chichester
Volume: 94
Issue: 2
Publisher DOI: 10.1002/jctb.5798
Page Start: 516
Page End: 526
EISSN: 1097-4660
ISSN: 0268-2575
Appears in Collections:FG Bioverfahrenstechnik » Publications

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