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

Authors
  • Legon, Laurence1, 2
  • Corre, Christophe2
  • Bates, Declan G1
  • Mannan, Ahmad A1
  • 1 Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick, Coventry, UK.
  • 2 Warwick Integrative Synthetic Biology Centre, School of Life Sciences, University of Warwick, Coventry, UK.
Type
Published Article
Journal
Bioinformatics (Oxford, England)
Publication Date
Jun 01, 2022
Identifiers
DOI: 10.1093/bioinformatics/btac376
PMID: 35642935
Source
Medline
Language
English
License
Unknown

Abstract

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. 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. 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 data are available at Bioinformatics online. © The Author(s) 2022. Published by Oxford University Press.

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