LAPSE:2025.0540v1
Published Article

LAPSE:2025.0540v1
Metabolic network reduction based on Extreme Pathway sets
June 27, 2025
Abstract
The use of metabolic networks is extremely valuable for design and optimisation of bioprocesses as they provide great insight into cellular metabolism. Within bioprocess optimisation, they have enabled better (economic) objective performance through more accurate network-based models. However, one of the drawbacks of using metabolic networks is their underdeterminacy, leading to non-unique flux distributions. Flux Balance Analysis (FBA) reduces this issue by making assumptions on the behaviour of the cell. However, for metabolic networks of higher complexity, can still struggle with underdeterminacy. Metabolic network reduction can remove or greatly reduce this effect but can be difficult, especially when data is limited. Structural analysis of the metabolic network through Elementary Flux Modes (EFM) or Extreme Pathways (EP) can help locate the relevant information within the network. This work presents a metabolic network reduction approach based on the EPs that best explain a small set of available measurements. Many of the reactions will not be active during the process and a significantly smaller network can therefore be constructed. A case study of oxygen-limited Escherichia coli is presented which showcases this approach, enabling accurate prediction of the process with much smaller network-based models. This leads to much lower complexity bioprocess models while keeping the necessary information on cellular metabolism for the given process.
The use of metabolic networks is extremely valuable for design and optimisation of bioprocesses as they provide great insight into cellular metabolism. Within bioprocess optimisation, they have enabled better (economic) objective performance through more accurate network-based models. However, one of the drawbacks of using metabolic networks is their underdeterminacy, leading to non-unique flux distributions. Flux Balance Analysis (FBA) reduces this issue by making assumptions on the behaviour of the cell. However, for metabolic networks of higher complexity, can still struggle with underdeterminacy. Metabolic network reduction can remove or greatly reduce this effect but can be difficult, especially when data is limited. Structural analysis of the metabolic network through Elementary Flux Modes (EFM) or Extreme Pathways (EP) can help locate the relevant information within the network. This work presents a metabolic network reduction approach based on the EPs that best explain a small set of available measurements. Many of the reactions will not be active during the process and a significantly smaller network can therefore be constructed. A case study of oxygen-limited Escherichia coli is presented which showcases this approach, enabling accurate prediction of the process with much smaller network-based models. This leads to much lower complexity bioprocess models while keeping the necessary information on cellular metabolism for the given process.
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Keywords
Biosystems, Model Reduction, Multiscale Modelling
Subject
Suggested Citation
Mores W, Bhonsale SS, Logist F, Impe JFV. Metabolic network reduction based on Extreme Pathway sets. Systems and Control Transactions 4:2417-2422 (2025) https://doi.org/10.69997/sct.132855
Author Affiliations
Mores W: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Bhonsale SS: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Logist F: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Impe JFV: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Bhonsale SS: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Logist F: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Impe JFV: BioTeC+ KU Leuven, Department of Chemical Engineering, Gent, Belgium
Journal Name
Systems and Control Transactions
Volume
4
First Page
2417
Last Page
2422
Year
2025
Publication Date
2025-07-01
Version Comments
Original Submission
Other Meta
PII: 2417-2422-1595-SCT-4-2025, Publication Type: Journal Article
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LAPSE:2025.0540v1
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https://doi.org/10.69997/sct.132855
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Jun 27, 2025
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References Cited
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