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Lookup NU author(s): Dr Jichun LiORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 by the authors.Bilevel modelling has been widely applied for the identification of genetic perturbations in metabolic engineering. However, most current approaches are based on a biased assumption that mutant strains always grow optimally. In addition, they are developed based on production rates, which may not meet yield requirements imposed on a production strain. This paper propose to design strains via multiobjective bilevel models that account for the tradeoff between cell growth and metabolic adjustments from the wild type strain. The proposed modelling frameworks can be used to identify design strategies that maximise rates and/or yields of target products, termed rate-based and yield-based modelling, respectively. We demonstrate, through in silico production of important chemicals in Escherichia coli, that our modelling approaches can generate growth-coupled designs in terms of rate and/or yield, and yield-based modelling identifies design strategies consistent with existing experimental studies as well as suggesting novel designs, thereby holding great promise for selecting targets for high-performance strain design. An important finding from this work that a growth rate coupled design is not necessarily growth yield coupled and vice versa suggests that growth-coupled designs should be analysed in both rate and yield spaces to determine their theoretical feasibility.
Author(s): Wang B, Jiang S, Xu S, Li J
Publication type: Article
Publication status: Published
Journal: Algorithms
Year: 2025
Volume: 18
Issue: 12
Online publication date: 12/12/2025
Acceptance date: 04/12/2025
Date deposited: 05/01/2026
ISSN (electronic): 1999-4893
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
URL: https://doi.org/10.3390/a18120786
DOI: 10.3390/a18120786
Data Access Statement: Source code implemented in the MATLAB Cobratoolbox is freely available at https://github.com/chang88ye/Knock-Tools (accessed on 3 December 2025)
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