We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Modelling concentration gradients in fed‐batch cultivations of E. coli – towards the flexible design of scale‐down experiments.
- Authors
Anane, Emmanuel; Sawatzki, Annina; Neubauer, Peter; Cruz‐Bournazou, Mariano Nicolas
- 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 with a reference cultivation. CONCLUSIONS: 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. © 2018 Society of Chemical Industry
- Subjects
BIOREACTORS; MICROBIAL physiology; AMINO acids; NORLEUCINE; ESCHERICHIA coli
- Publication
Journal of Chemical Technology & Biotechnology, 2019, Vol 94, Issue 2, p516
- ISSN
0268-2575
- Publication type
Article
- DOI
10.1002/jctb.5798