{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:27:30Z","timestamp":1772814450499,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1007817","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["NIH R01 GM057089"],"award-info":[{"award-number":["NIH R01 GM057089"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["NIH 1-U01-AI124316"],"award-info":[{"award-number":["NIH 1-U01-AI124316"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006132","name":"Office of Science","doi-asserted-by":"publisher","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}],"id":[{"id":"10.13039\/100006132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Sustaining a robust metabolic network requires a balanced and fully functioning proteome. In addition to amino acids, many enzymes require cofactors (coenzymes and engrafted prosthetic groups) to function properly. Extensively validated resource allocation models, such as genome-scale models of metabolism and gene expression (ME-models), have the ability to compute an optimal proteome composition underlying a metabolic phenotype, including the provision of all required cofactors. Here we apply the ME-model for\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    K-12 MG1655 to computationally examine how environmental conditions change the proteome and its accompanying cofactor usage. We found that: (1) The cofactor requirements computed by the ME-model mostly agree with the standard biomass objective function used in models of metabolism alone (M-models); (2) ME-model computations reveal non-intuitive variability in cofactor use under different growth conditions; (3) An analysis of ME-model predicted protein use in aerobic and anaerobic conditions suggests an enrichment in the use of peroxyl scavenging acids in the proteins used to sustain aerobic growth; (4) The ME-model could describe how limitation in key protein components affect the metabolic state of\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    . Genome-scale models have thus reached a level of sophistication where they reveal intricate properties of functional proteomes and how they support different\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    lifestyles.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1007817","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T16:06:02Z","timestamp":1624464362000},"page":"e1007817","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-6345","authenticated-orcid":true,"given":"Colton J.","family":"Lloyd","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-8949","authenticated-orcid":true,"given":"Jonathan","family":"Monk","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6663-7643","authenticated-orcid":true,"given":"Laurence","family":"Yang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-2128","authenticated-orcid":true,"given":"Ali","family":"Ebrahim","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-6785","authenticated-orcid":true,"given":"Bernhard O.","family":"Palsson","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"pcbi.1007817.ref001","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nrg3643","article-title":"Constraint-based models predict metabolic and associated cellular functions","volume":"15","author":"A Bordbar","year":"2014","journal-title":"Nat Rev Genet"},{"key":"pcbi.1007817.ref002","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cell.2015.05.019","article-title":"Using Genome-scale Models to Predict Biological Capabilities","volume":"161","author":"EJ O\u2019Brien","year":"2015","journal-title":"Cell"},{"key":"pcbi.1007817.ref003","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrmicro2737","article-title":"Constraining the metabolic genotype\u2013phenotype relationship using a phylogeny of in silico methods","volume":"10","author":"NE Lewis","year":"2012","journal-title":"Nat Rev Microbiol"},{"key":"pcbi.1007817.ref004","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/msb.2013.18","article-title":"Basic and applied uses of genome-scale metabolic network reconstructions of Escherichia coli","volume":"9","author":"D McCloskey","year":"2013","journal-title":"Mol Syst Biol"},{"key":"pcbi.1007817.ref005","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.mib.2010.03.003","article-title":"The biomass objective function","volume":"13","author":"AM Feist","year":"2010","journal-title":"Curr Opin Microbiol"},{"key":"pcbi.1007817.ref006","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/j.1432-1033.1995.0525h.x","article-title":"Transketolase A of Escherichia coli K12. 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