Cargando…

OptEnvelope: A target point guided method for growth-coupled production using knockouts

Finding the best knockout strategy for coupling biomass growth and production of a target metabolite using a mathematic model of metabolism is a challenge in biotechnology. In this research, a three-step method named OptEnvelope is presented based on finding minimal set of active reactions for a tar...

Descripción completa

Detalles Bibliográficos
Autores principales: Motamedian, Ehsan, Berzins, Kristaps, Muiznieks, Reinis, Stalidzans, Egils
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653430/
https://www.ncbi.nlm.nih.gov/pubmed/37972019
http://dx.doi.org/10.1371/journal.pone.0294313
_version_ 1785147775542886400
author Motamedian, Ehsan
Berzins, Kristaps
Muiznieks, Reinis
Stalidzans, Egils
author_facet Motamedian, Ehsan
Berzins, Kristaps
Muiznieks, Reinis
Stalidzans, Egils
author_sort Motamedian, Ehsan
collection PubMed
description Finding the best knockout strategy for coupling biomass growth and production of a target metabolite using a mathematic model of metabolism is a challenge in biotechnology. In this research, a three-step method named OptEnvelope is presented based on finding minimal set of active reactions for a target point in the feasible solution space (envelope) using a mixed-integer linear programming formula. The method initially finds the reduced desirable solution space envelope in the product versus biomass plot by removing all inactive reactions. Then, with reinsertion of the deleted reactions, OptEnvelope attempts to reduce the number of knockouts so that the desirable production envelope is preserved. Additionally, OptEnvelope searches for envelopes with higher minimum production rates or fewer knockouts by evaluating different target points within the desired solution space. It is possible to limit the maximal number of knockouts. The method was implemented on metabolic models of E. coli and S. cerevisiae to test the method benchmarking the capability of these industrial microbes for overproduction of acetate and glycerol under aerobic conditions and succinate and ethanol under anaerobic conditions. The results illustrate that OptEnvelope is capable to find multiple strong coupled envelopes located in the desired solution space because of its novel target point oriented strategy of envelope search. The results indicate that E. coli is more appropriate to produce acetate and succinate while S. cerevisiae is a better host for glycerol production. Gene deletions for some of the proposed reaction knockouts have been previously reported to increase the production of these metabolites in experiments. Both organisms are suitable for ethanol production, however, more knockouts for the adaptation of E. coli are required. OptEnvelope is available at https://github.com/lv-csbg/optEnvelope.
format Online
Article
Text
id pubmed-10653430
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-106534302023-11-16 OptEnvelope: A target point guided method for growth-coupled production using knockouts Motamedian, Ehsan Berzins, Kristaps Muiznieks, Reinis Stalidzans, Egils PLoS One Research Article Finding the best knockout strategy for coupling biomass growth and production of a target metabolite using a mathematic model of metabolism is a challenge in biotechnology. In this research, a three-step method named OptEnvelope is presented based on finding minimal set of active reactions for a target point in the feasible solution space (envelope) using a mixed-integer linear programming formula. The method initially finds the reduced desirable solution space envelope in the product versus biomass plot by removing all inactive reactions. Then, with reinsertion of the deleted reactions, OptEnvelope attempts to reduce the number of knockouts so that the desirable production envelope is preserved. Additionally, OptEnvelope searches for envelopes with higher minimum production rates or fewer knockouts by evaluating different target points within the desired solution space. It is possible to limit the maximal number of knockouts. The method was implemented on metabolic models of E. coli and S. cerevisiae to test the method benchmarking the capability of these industrial microbes for overproduction of acetate and glycerol under aerobic conditions and succinate and ethanol under anaerobic conditions. The results illustrate that OptEnvelope is capable to find multiple strong coupled envelopes located in the desired solution space because of its novel target point oriented strategy of envelope search. The results indicate that E. coli is more appropriate to produce acetate and succinate while S. cerevisiae is a better host for glycerol production. Gene deletions for some of the proposed reaction knockouts have been previously reported to increase the production of these metabolites in experiments. Both organisms are suitable for ethanol production, however, more knockouts for the adaptation of E. coli are required. OptEnvelope is available at https://github.com/lv-csbg/optEnvelope. Public Library of Science 2023-11-16 /pmc/articles/PMC10653430/ /pubmed/37972019 http://dx.doi.org/10.1371/journal.pone.0294313 Text en © 2023 Motamedian et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Motamedian, Ehsan
Berzins, Kristaps
Muiznieks, Reinis
Stalidzans, Egils
OptEnvelope: A target point guided method for growth-coupled production using knockouts
title OptEnvelope: A target point guided method for growth-coupled production using knockouts
title_full OptEnvelope: A target point guided method for growth-coupled production using knockouts
title_fullStr OptEnvelope: A target point guided method for growth-coupled production using knockouts
title_full_unstemmed OptEnvelope: A target point guided method for growth-coupled production using knockouts
title_short OptEnvelope: A target point guided method for growth-coupled production using knockouts
title_sort optenvelope: a target point guided method for growth-coupled production using knockouts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653430/
https://www.ncbi.nlm.nih.gov/pubmed/37972019
http://dx.doi.org/10.1371/journal.pone.0294313
work_keys_str_mv AT motamedianehsan optenvelopeatargetpointguidedmethodforgrowthcoupledproductionusingknockouts
AT berzinskristaps optenvelopeatargetpointguidedmethodforgrowthcoupledproductionusingknockouts
AT muiznieksreinis optenvelopeatargetpointguidedmethodforgrowthcoupledproductionusingknockouts
AT stalidzansegils optenvelopeatargetpointguidedmethodforgrowthcoupledproductionusingknockouts