Giving the cells what they need when they need it: Biosensor-based feeding control.
Escherichia coli
biosensor
nitrogen starvation
online flow cytometry
process control
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
23 Jan 2024
23 Jan 2024
Historique:
revised:
11
12
2023
received:
28
07
2023
accepted:
04
01
2024
medline:
23
1
2024
pubmed:
23
1
2024
entrez:
23
1
2024
Statut:
aheadofprint
Résumé
"Giving the cells exactly what they need, when they need it" is the core idea behind the proposed bioprocess control strategy: operating bioprocess based on the physiological behavior of the microbial population rather than exclusive monitoring of environmental parameters. We are envisioning to achieve this through the use of genetically encoded biosensors combined with online flow cytometry (FCM) to obtain a time-dependent "physiological fingerprint" of the population. We developed a biosensor based on the glnA promoter (glnAp) and applied it for monitoring the nitrogen-related nutritional state of Escherichia coli. The functionality of the biosensor was demonstrated through multiple cultivation runs performed at various scales-from microplate to 20 L bioreactor. We also developed a fully automated bioreactor-FCM interface for on-line monitoring of the microbial population. Finally, we validated the proposed strategy by performing a fed-batch experiment where the biosensor signal is used as the actuator for a nitrogen feeding feedback control. This new generation of process control, -based on the specific needs of the cells, -opens the possibility of improving process development on a short timescale and therewith, the robustness and performance of fermentation processes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : GlaxoSmithKline
Organisme : Wagralim-Biowin
Informations de copyright
© 2024 Wiley Periodicals LLC.
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