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Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model
BACKGROUND: The halophilic bacterium Chromohalobacter salexigens is a natural producer of ectoines, compatible solutes with current and potential biotechnological applications. As production of ectoines is an osmoregulated process that draws away TCA intermediates, bacterial metabolism needs to be a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759318/ https://www.ncbi.nlm.nih.gov/pubmed/29316921 http://dx.doi.org/10.1186/s12934-017-0852-0 |
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author | Piubeli, Francine Salvador, Manuel Argandoña, Montserrat Nieto, Joaquín J. Bernal, Vicente Pastor, Jose M. Cánovas, Manuel Vargas, Carmen |
author_facet | Piubeli, Francine Salvador, Manuel Argandoña, Montserrat Nieto, Joaquín J. Bernal, Vicente Pastor, Jose M. Cánovas, Manuel Vargas, Carmen |
author_sort | Piubeli, Francine |
collection | PubMed |
description | BACKGROUND: The halophilic bacterium Chromohalobacter salexigens is a natural producer of ectoines, compatible solutes with current and potential biotechnological applications. As production of ectoines is an osmoregulated process that draws away TCA intermediates, bacterial metabolism needs to be adapted to cope with salinity changes. To explore and use C. salexigens as cell factory for ectoine(s) production, a comprehensive knowledge at the systems level of its metabolism is essential. For this purpose, the construction of a robust and high-quality genome-based metabolic model of C. salexigens was approached. RESULTS: We generated and validated a high quality genome-based C. salexigens metabolic model (iFP764). This comprised an exhaustive reconstruction process based on experimental information, analysis of genome sequence, manual re-annotation of metabolic genes, and in-depth refinement. The model included three compartments (periplasmic, cytoplasmic and external medium), and two salinity-specific biomass compositions, partially based on experimental results from C. salexigens. Using previous metabolic data as constraints, the metabolic model allowed us to simulate and analyse the metabolic osmoadaptation of C. salexigens under conditions for low and high production of ectoines. The iFP764 model was able to reproduce the major metabolic features of C. salexigens. Flux Balance Analysis (FBA) and Monte Carlo Random sampling analysis showed salinity-specific essential metabolic genes and different distribution of fluxes and variation in the patterns of correlation of reaction sets belonging to central C and N metabolism, in response to salinity. Some of them were related to bioenergetics or production of reducing equivalents, and probably related to demand for ectoines. Ectoines metabolic reactions were distributed according to its correlation in four modules. Interestingly, the four modules were independent both at low and high salinity conditions, as they did not correlate to each other, and they were not correlated with other subsystems. CONCLUSIONS: Our validated model is one of the most complete curated networks of halophilic bacteria. It is a powerful tool to simulate and explore C. salexigens metabolism at low and high salinity conditions, driving to low and high production of ectoines. In addition, it can be useful to optimize the metabolism of other halophilic bacteria for metabolite production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-017-0852-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5759318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57593182018-01-10 Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model Piubeli, Francine Salvador, Manuel Argandoña, Montserrat Nieto, Joaquín J. Bernal, Vicente Pastor, Jose M. Cánovas, Manuel Vargas, Carmen Microb Cell Fact Research BACKGROUND: The halophilic bacterium Chromohalobacter salexigens is a natural producer of ectoines, compatible solutes with current and potential biotechnological applications. As production of ectoines is an osmoregulated process that draws away TCA intermediates, bacterial metabolism needs to be adapted to cope with salinity changes. To explore and use C. salexigens as cell factory for ectoine(s) production, a comprehensive knowledge at the systems level of its metabolism is essential. For this purpose, the construction of a robust and high-quality genome-based metabolic model of C. salexigens was approached. RESULTS: We generated and validated a high quality genome-based C. salexigens metabolic model (iFP764). This comprised an exhaustive reconstruction process based on experimental information, analysis of genome sequence, manual re-annotation of metabolic genes, and in-depth refinement. The model included three compartments (periplasmic, cytoplasmic and external medium), and two salinity-specific biomass compositions, partially based on experimental results from C. salexigens. Using previous metabolic data as constraints, the metabolic model allowed us to simulate and analyse the metabolic osmoadaptation of C. salexigens under conditions for low and high production of ectoines. The iFP764 model was able to reproduce the major metabolic features of C. salexigens. Flux Balance Analysis (FBA) and Monte Carlo Random sampling analysis showed salinity-specific essential metabolic genes and different distribution of fluxes and variation in the patterns of correlation of reaction sets belonging to central C and N metabolism, in response to salinity. Some of them were related to bioenergetics or production of reducing equivalents, and probably related to demand for ectoines. Ectoines metabolic reactions were distributed according to its correlation in four modules. Interestingly, the four modules were independent both at low and high salinity conditions, as they did not correlate to each other, and they were not correlated with other subsystems. CONCLUSIONS: Our validated model is one of the most complete curated networks of halophilic bacteria. It is a powerful tool to simulate and explore C. salexigens metabolism at low and high salinity conditions, driving to low and high production of ectoines. In addition, it can be useful to optimize the metabolism of other halophilic bacteria for metabolite production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-017-0852-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-09 /pmc/articles/PMC5759318/ /pubmed/29316921 http://dx.doi.org/10.1186/s12934-017-0852-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Piubeli, Francine Salvador, Manuel Argandoña, Montserrat Nieto, Joaquín J. Bernal, Vicente Pastor, Jose M. Cánovas, Manuel Vargas, Carmen Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title | Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title_full | Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title_fullStr | Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title_full_unstemmed | Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title_short | Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model |
title_sort | insights into metabolic osmoadaptation of the ectoines-producer bacterium chromohalobacter salexigens through a high-quality genome scale metabolic model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759318/ https://www.ncbi.nlm.nih.gov/pubmed/29316921 http://dx.doi.org/10.1186/s12934-017-0852-0 |
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