{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:12Z","timestamp":1772138052943,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/L016494\/1"],"award-info":[{"award-number":["EP\/L016494\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M017982\/1"],"award-info":[{"award-number":["BB\/M017982\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>A widely applicable strategy to create cell factories is to knockout (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 synthesize 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To address this multi-objective optimization problem, we developed a software tool named gcFront\u2014using a genetic algorithm it explores KOs that maximize 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\u2014granting users flexibility in selecting designs to take to the lab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac376","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T08:25:27Z","timestamp":1654071927000},"page":"3657-3659","source":"Crossref","is-referenced-by-count":11,"title":["gcFront: a tool for determining a Pareto front of growth-coupled cell factory designs"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2568-9513","authenticated-orcid":false,"given":"Laurence","family":"Legon","sequence":"first","affiliation":[{"name":"Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick , Coventry CV4 7AL, UK"},{"name":"Warwick Integrative Synthetic Biology Centre, School of Life Sciences, University of Warwick , Coventry CV4 7AL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-9315","authenticated-orcid":false,"given":"Christophe","family":"Corre","sequence":"additional","affiliation":[{"name":"Warwick Integrative Synthetic Biology Centre, School of Life Sciences, University of Warwick , Coventry CV4 7AL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-9846","authenticated-orcid":false,"given":"Declan G","family":"Bates","sequence":"additional","affiliation":[{"name":"Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick , Coventry CV4 7AL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-8416","authenticated-orcid":false,"given":"Ahmad A","family":"Mannan","sequence":"additional","affiliation":[{"name":"Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick , Coventry CV4 7AL, UK"}]}],"member":"286","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"2023041405362631300_","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s12859-019-2946-7","article-title":"Determination of growth-coupling strategies and their underlying principles","volume":"20","author":"Alter","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"2023041405362631300_","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12859-020-3377-1","article-title":"MOMO\u2014multi-objective metabolic mixed integer optimization: application to yeast strain engineering","volume":"21","author":"Andrade","year":"2020","journal-title":"BMC Bioinformatics"},{"key":"2023041405362631300_","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s42003-018-0076-9","article-title":"An automated design-build-test-learn pipeline for enhanced microbial production of fine chemicals","volume":"1","author":"Carbonell","year":"2018","journal-title":"Commun. 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