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gcFront : a tool for determining a Pareto front of growth-coupled cell factory designs

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Legon, Laurence, Corre, Christophe, Bates, Declan G. and Mannan, Ahmad A. (2022) gcFront : a tool for determining a Pareto front of growth-coupled cell factory designs. Bioinformatics, 38 (14). pp. 3657-3659. doi:10.1093/bioinformatics/btac376 ISSN 1460-2059.

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Official URL: https://doi.org/10.1093/bioinformatics/btac376

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Abstract

Motivation A widely applicable strategy to create cell factories is to knock out (KO) genes or reactions to redirect cell metabolism so that chemical synthesis is made obligatory when the cell grows at its maximum rate. Synthesis is thus growth-coupled, and the stronger the coupling the more deleterious any impediments in synthesis are to cell growth, making high producer phenotypes evolutionarily robust. Additionally, we desire that these strains grow and synthesise at high rates. Genome-scale metabolic models can be used to explore and identify KOs that growth-couple synthesis, but these are rare in an immense design space, making the search difficult and slow. Results To address this multi-objective optimization problem, we developed a software tool named gcFront - using a genetic algorithm it explores KOs that maximise cell growth, product synthesis, and coupling strength. Moreover, our measure of coupling strength facilitates the search so that gcFront not only finds a growth coupled design in minutes but also outputs many alternative Pareto optimal designs from a single run - granting users flexibility in selecting designs to take to the lab. Availability gcFront, with documentation and a workable tutorial, is freely available at GitHub: https://github.com/lLegon/gcFront and archived at Zenodo, DOI: 10.5281/zenodo.5557755 (Legon et al., 2022). Supplementary information Supplementary data are available at Bioinformatics online.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Cell metabolism , Biological control systems, Cells -- Growth -- Regulation, Bioinformatics
Journal or Publication Title: Bioinformatics
Publisher: Oxford University Press (OUP)
ISSN: 1460-2059
Official Date: July 2022
Dates:
DateEvent
July 2022Published
1 June 2022Available
30 May 2022Accepted
Volume: 38
Number: 14
Page Range: pp. 3657-3659
DOI: 10.1093/bioinformatics/btac376
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 18 August 2022
Date of first compliant Open Access: 18 August 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
EP/L016494/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
BB/M017982/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
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