Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency

Julian Kager; Nora  Horst; Christoph Herwig; Ioannis V. Skiadas

doi:10.1016/B978-0-443-15274-0.50414-5

Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency

Julian Kager^*
, Nora Horst
, Christoph Herwig
, Ioannis V. Skiadas

^*Corresponding author for this work

TU Wien

Research output: Chapter in Book/Report/Conference proceeding › Article in proceedings › Research › peer-review

Abstract

Within this contribution we use a mechanistic model to optimize the feed addition and harvest time point of the induction phase of a recombinantly produced protein in E. coli. The model includes the metabolic load of the forced product formation and its effects on the production rate as well as the biomass conversion yield. The model was fitted to three experiments with different constant substrate feed rates during the production phase. Under usage of the calibrated model, optimal substrate addition and harvest time points with the objective to improve the time-space yield were determined. In addition, a constant feed rate was compared to an increasing feed rate with the aim to maintain a constant biomass specific substrate uptake. Different optimal combinations were identified and compared considering time and resource efficiency. The work shows how recombinant protein production and the inevitable metabolic load can be incorporated into a simple mechanistic model. Once calibrated to a limited number of experiments the model is suited for the design of a resource and time optimal induction phase. Future experiments and uncertainty analysis will show how well the model predicted the real optimal operating points.

Original language	English
Title of host publication	Proceedings of the 33rd European Symposium on Computer Aided Process Engineering
Editors	Antonis Kokossis, Michael C. Georgiadis, Efstratios N. Pistikopoulos
Publisher	Elsevier
Publication date	2023
Pages	2607-2612
ISBN (Print)	978-0-443-23553-5, 978-0-443-15274-0
DOIs	https://doi.org/10.1016/B978-0-443-15274-0.50414-5
Publication status	Published - 2023
Event	33rd European Symposium on Computer Aided Process Engineering - Athens, Greece Duration: 18 Jun 2023 → 21 Jun 2023

Conference

Conference	33rd European Symposium on Computer Aided Process Engineering
Country/Territory	Greece
City	Athens
Period	18/06/2023 → 21/06/2023

Series	Computer Aided Chemical Engineering
Volume	52
ISSN	1570-7946

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 8 Decent Work and Economic Growth
SDG 12 Responsible Consumption and Production

Keywords

Bioprocessing
Optimization
Production phase modelling
Simulation
Recombinant protein production

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10.1016/B978-0-443-15274-0.50414-5

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Kager, J., Horst, N., Herwig, C., & Skiadas, I. V. (2023). Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency. In A. Kokossis, M. C. Georgiadis, & E. N. Pistikopoulos (Eds.), Proceedings of the 33rd European Symposium on Computer Aided Process Engineering (pp. 2607-2612). Elsevier. https://doi.org/10.1016/B978-0-443-15274-0.50414-5

Kager, Julian ; Horst, Nora ; Herwig, Christoph et al. / Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency. Proceedings of the 33rd European Symposium on Computer Aided Process Engineering. editor / Antonis Kokossis ; Michael C. Georgiadis ; Efstratios N. Pistikopoulos. Elsevier, 2023. pp. 2607-2612 (Computer Aided Chemical Engineering, Vol. 52).

@inproceedings{ede3ad48f54e44caba10d7fda23e5c9f,

title = "Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency",

abstract = "Within this contribution we use a mechanistic model to optimize the feed addition and harvest time point of the induction phase of a recombinantly produced protein in E. coli. The model includes the metabolic load of the forced product formation and its effects on the production rate as well as the biomass conversion yield. The model was fitted to three experiments with different constant substrate feed rates during the production phase. Under usage of the calibrated model, optimal substrate addition and harvest time points with the objective to improve the time-space yield were determined. In addition, a constant feed rate was compared to an increasing feed rate with the aim to maintain a constant biomass specific substrate uptake. Different optimal combinations were identified and compared considering time and resource efficiency. The work shows how recombinant protein production and the inevitable metabolic load can be incorporated into a simple mechanistic model. Once calibrated to a limited number of experiments the model is suited for the design of a resource and time optimal induction phase. Future experiments and uncertainty analysis will show how well the model predicted the real optimal operating points.",

keywords = "Bioprocessing, Optimization, Production phase modelling, Simulation, Recombinant protein production",

author = "Julian Kager and Nora Horst and Christoph Herwig and Skiadas, \{Ioannis V.\}",

year = "2023",

doi = "10.1016/B978-0-443-15274-0.50414-5",

language = "English",

isbn = "978-0-443-23553-5",

series = "Computer Aided Chemical Engineering",

publisher = "Elsevier",

pages = "2607--2612",

editor = "Kokossis, \{Antonis \} and \{C. Georgiadis\}, \{Michael \} and \{N. Pistikopoulos\}, Efstratios",

booktitle = "Proceedings of the 33rd European Symposium on Computer Aided Process Engineering",

address = "United Kingdom",

note = "33rd European Symposium on Computer Aided Process Engineering, ESCAPE33 ; Conference date: 18-06-2023 Through 21-06-2023",

}

Kager, J, Horst, N, Herwig, C & Skiadas, IV 2023, Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency. in A Kokossis, M C. Georgiadis & E N. Pistikopoulos (eds), Proceedings of the 33rd European Symposium on Computer Aided Process Engineering. Elsevier, Computer Aided Chemical Engineering, vol. 52, pp. 2607-2612, 33rd European Symposium on Computer Aided Process Engineering, Athens, Greece, 18/06/2023. https://doi.org/10.1016/B978-0-443-15274-0.50414-5

Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency. / Kager, Julian; Horst, Nora ; Herwig, Christoph et al.
Proceedings of the 33rd European Symposium on Computer Aided Process Engineering. ed. / Antonis Kokossis; Michael C. Georgiadis; Efstratios N. Pistikopoulos. Elsevier, 2023. p. 2607-2612 (Computer Aided Chemical Engineering, Vol. 52).

Research output: Chapter in Book/Report/Conference proceeding › Article in proceedings › Research › peer-review

TY - GEN

T1 - Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency

AU - Kager, Julian

AU - Horst, Nora

AU - Herwig, Christoph

AU - Skiadas, Ioannis V.

PY - 2023

Y1 - 2023

N2 - Within this contribution we use a mechanistic model to optimize the feed addition and harvest time point of the induction phase of a recombinantly produced protein in E. coli. The model includes the metabolic load of the forced product formation and its effects on the production rate as well as the biomass conversion yield. The model was fitted to three experiments with different constant substrate feed rates during the production phase. Under usage of the calibrated model, optimal substrate addition and harvest time points with the objective to improve the time-space yield were determined. In addition, a constant feed rate was compared to an increasing feed rate with the aim to maintain a constant biomass specific substrate uptake. Different optimal combinations were identified and compared considering time and resource efficiency. The work shows how recombinant protein production and the inevitable metabolic load can be incorporated into a simple mechanistic model. Once calibrated to a limited number of experiments the model is suited for the design of a resource and time optimal induction phase. Future experiments and uncertainty analysis will show how well the model predicted the real optimal operating points.

AB - Within this contribution we use a mechanistic model to optimize the feed addition and harvest time point of the induction phase of a recombinantly produced protein in E. coli. The model includes the metabolic load of the forced product formation and its effects on the production rate as well as the biomass conversion yield. The model was fitted to three experiments with different constant substrate feed rates during the production phase. Under usage of the calibrated model, optimal substrate addition and harvest time points with the objective to improve the time-space yield were determined. In addition, a constant feed rate was compared to an increasing feed rate with the aim to maintain a constant biomass specific substrate uptake. Different optimal combinations were identified and compared considering time and resource efficiency. The work shows how recombinant protein production and the inevitable metabolic load can be incorporated into a simple mechanistic model. Once calibrated to a limited number of experiments the model is suited for the design of a resource and time optimal induction phase. Future experiments and uncertainty analysis will show how well the model predicted the real optimal operating points.

KW - Bioprocessing

KW - Optimization

KW - Production phase modelling

KW - Simulation

KW - Recombinant protein production

U2 - 10.1016/B978-0-443-15274-0.50414-5

DO - 10.1016/B978-0-443-15274-0.50414-5

M3 - Article in proceedings

SN - 978-0-443-23553-5

SN - 978-0-443-15274-0

T3 - Computer Aided Chemical Engineering

SP - 2607

EP - 2612

BT - Proceedings of the 33rd European Symposium on Computer Aided Process Engineering

A2 - Kokossis, Antonis

A2 - C. Georgiadis, Michael

A2 - N. Pistikopoulos, Efstratios

PB - Elsevier

T2 - 33rd European Symposium on Computer Aided Process Engineering

Y2 - 18 June 2023 through 21 June 2023

ER -

Kager J, Horst N, Herwig C, Skiadas IV. Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency. In Kokossis A, C. Georgiadis M, N. Pistikopoulos E, editors, Proceedings of the 33rd European Symposium on Computer Aided Process Engineering. Elsevier. 2023. p. 2607-2612. (Computer Aided Chemical Engineering, Vol. 52). doi: 10.1016/B978-0-443-15274-0.50414-5

Model-based optimization of a recombinant E. coli fed-batch process for best time-space yield and conversion efficiency

Abstract

Conference

UN SDGs

Keywords

Access to Document

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