{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:09:24Z","timestamp":1772172564284,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1007694","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L013940\/1"],"award-info":[{"award-number":["BB\/L013940\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L013940\/1"],"award-info":[{"award-number":["BB\/L013940\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Nottingham\u2019s School of Life Sciences","award":["PhD studentship"],"award-info":[{"award-number":["PhD studentship"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Metabolic engineering in the post-genomic era is characterised by the development of new methods for metabolomics and fluxomics, supported by the integration of genetic engineering tools and mathematical modelling. Particularly, constraint-based stoichiometric models have been widely studied: (i) flux balance analysis (FBA) (\n                    <jats:italic>in silico<\/jats:italic>\n                    ), and (ii) metabolic flux analysis (MFA) (\n                    <jats:italic>in vivo<\/jats:italic>\n                    ). Recent studies have enabled the incorporation of thermodynamics and metabolomics data to improve the predictive capabilities of these approaches. However, an in-depth comparison and evaluation of these methods is lacking. This study presents a thorough analysis of two different\n                    <jats:italic>in silico<\/jats:italic>\n                    methods tested against experimental data (metabolomics and\n                    <jats:sup>13<\/jats:sup>\n                    C-MFA) for the mesophile\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    . In particular, a modified version of the recently published matTFA toolbox was created, providing a broader range of physicochemical parameters. Validating against experimental data allowed the determination of the best physicochemical parameters to perform the TFA (Thermodynamics-based Flux Analysis). An analysis of flux pattern changes in the central carbon metabolism between\n                    <jats:sup>13<\/jats:sup>\n                    C-MFA and TFA highlighted the limited capabilities of both approaches for elucidating the anaplerotic fluxes. In addition, a method based on centrality measures was suggested to identify important metabolites that (if quantified) would allow to further constrain the TFA. Finally, this study emphasised the need for standardisation in the fluxomics community: novel approaches are frequently released but a thorough comparison with currently accepted methods is not always performed.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1007694","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T13:59:23Z","timestamp":1611583163000},"page":"e1007694","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Physicochemical and metabolic constraints for thermodynamics-based stoichiometric modelling under mesophilic growth conditions"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3611-2130","authenticated-orcid":true,"given":"Claudio","family":"Tomi-Andrino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-3698","authenticated-orcid":true,"given":"Rupert","family":"Norman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-4142","authenticated-orcid":true,"given":"Thomas","family":"Millat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Soucaille","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Winzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-8375","authenticated-orcid":true,"given":"John","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-2130","authenticated-orcid":true,"given":"Dong-Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"issue":"10","key":"pcbi.1007694.ref001","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt1016","article-title":"Exploiting biological complexity for strain improvement through systems biology","volume":"22","author":"G Stephanopoulos","year":"2004","journal-title":"Nat Biotechnol"},{"key":"pcbi.1007694.ref002","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/bies.10385","article-title":"Here is the evidence, now what is the hypothesis? 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