{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:13:42Z","timestamp":1778058822791,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1006848","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T00:00:00Z","timestamp":1553212800000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006206","name":"Biological and Environmental Research","doi-asserted-by":"publisher","award":["DE-SC0012586"],"award-info":[{"award-number":["DE-SC0012586"]}],"id":[{"id":"10.13039\/100006206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","award":["NNF16CC0021858"],"award-info":[{"award-number":["NNF16CC0021858"]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of California, San Diego Frontiers in Innovation Scholars Program","award":["G2093"],"award-info":[{"award-number":["G2093"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1006848","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T19:37:30Z","timestamp":1551987450000},"page":"e1006848","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":56,"title":["Predicting proteome allocation, overflow metabolism, and metal requirements in a model acetogen"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9973-524X","authenticated-orcid":true,"given":"Joanne K.","family":"Liu","sequence":"first","affiliation":[]},{"given":"Colton","family":"Lloyd","sequence":"additional","affiliation":[]},{"given":"Mahmoud M.","family":"Al-Bassam","sequence":"additional","affiliation":[]},{"given":"Ali","family":"Ebrahim","sequence":"additional","affiliation":[]},{"given":"Ji-Nu","family":"Kim","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-0446","authenticated-orcid":true,"given":"Connor","family":"Olson","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Aksenov","sequence":"additional","affiliation":[]},{"given":"Pieter","family":"Dorrestein","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-3296","authenticated-orcid":true,"given":"Karsten","family":"Zengler","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.febslet.2012.04.043","article-title":"Pathway engineering and synthetic biology using acetogens","volume":"586","author":"B Schiel-Bengelsdorf","year":"2012","journal-title":"FEBS Lett"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.copbio.2013.12.001","article-title":"Trash to treasure: production of biofuels and commodity chemicals via syngas fermenting microorganisms","volume":"27","author":"H Latif","year":"2014","journal-title":"Curr Opin Biotechnol"},{"key":"ref3","first-page":"1","author":"K K\u00fcsel","year":"2011"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/nrmicro3365","article-title":"Autotrophy at the thermodynamic limit of life: a model for energy conservation in acetogenic bacteria","volume":"12","author":"K Schuchmann","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1475-2859-12-118","article-title":"Characterizing acetogenic metabolism using a genome-scale metabolic reconstruction of <italic>Clostridium ljungdahlii<\/italic>","volume":"12","author":"H Nagarajan","year":"2013","journal-title":"Microb Cell Fact"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cels.2017.04.008","article-title":"Maintenance of ATP homeostasis triggers metabolic shifts in gas-fermenting acetogens","volume":"4","author":"K Valgepea","year":"2017","journal-title":"Cell Syst"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ymben.2017.04.007","article-title":"Arginine deiminase pathway provides ATP and boosts growth of the gas-fermenting acetogen <italic>Clostridium autoethanogenum<\/italic>","volume":"41","author":"K Valgepea","year":"2017","journal-title":"Metab Eng"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C5IB00095E","article-title":"Investigating <italic>Moorella thermoacetica<\/italic> metabolism with a genome-scale constraint-based metabolic model","volume":"7","author":"MA Islam","year":"2015","journal-title":"Integr Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12918-014-0110-6","article-title":"Reconstruction and modeling protein translocation and compartmentalization in <italic>Escherichia coli<\/italic> at the genome-scale","volume":"8","author":"JK Liu","year":"2014","journal-title":"BMC Syst Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/msb.2013.52","article-title":"Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction","volume":"9","author":"EJ O\u2019Brien","year":"2014","journal-title":"Mol Syst Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.1128\/AEM.00355-11","article-title":"2,3-Butanediol production by acetogenic bacteria, an alternative route to chemical synthesis, using industrial waste gas","volume":"77","author":"M Kopke","year":"2011","journal-title":"Appl Environ Microbiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nchembio0308-145","article-title":"Assembling the pieces","volume":"4","author":"DJ Thiele","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nchembio0807-447","article-title":"Systems chemical biology","volume":"3","author":"TI Oprea","year":"2007","journal-title":"Nat Chem Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/j.bbapap.2008.08.012","article-title":"Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation","volume":"1784","author":"SW Ragsdale","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.febslet.2011.09.031","article-title":"Hydrogen, metals, bifurcating electrons, and proton gradients: The early evolution of biological energy conservation","volume":"586","author":"WF Martin","year":"2012","journal-title":"FEBS Lett"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/BF02919018","article-title":"Biological production of ethanol from coal synthesis gas","volume":"38","author":"JR Phillips","year":"1993","journal-title":"Appl Biochem Biotechnol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1039\/c1mt00042j","article-title":"Metal centers in the anaerobic microbial metabolism of CO and CO2","author":"G Bender","year":"2011","journal-title":"Metallomics"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1128\/JB.00399-15","article-title":"Energy conservation associated with ethanol formation from H<sub>2<\/sub> and CO<sub>2<\/sub> in <italic>Clostridium autoethanogenum<\/italic> involving electron bifurcation. Metcalf WW, editor","volume":"197","author":"J Mock","year":"2015","journal-title":"J Bacteriol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.enzmictec.2015.06.011","article-title":"Characterization of an acetoin reductase\/2,3-butanediol dehydrogenase from <italic>Clostridium ljungdahlii<\/italic> DSM 13528","volume":"79\u201380","author":"Y Tan","year":"2015","journal-title":"Enzyme Microb Technol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"T Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"13087","DOI":"10.1073\/pnas.1004716107","article-title":"<italic>Clostridium ljungdahlii<\/italic> represents a microbial production platform based on syngas","volume":"107","author":"M K\u00f6pke","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2180-5-8","article-title":"The RAST Server: Rapid Annotations using Subsystems Technology","volume":"5","author":"SA Becker","year":"2005","journal-title":"BMC Microbiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/ncomms1928","article-title":"<italic>In silico<\/italic> method for modelling metabolism and gene product expression at genome scale","volume":"3","author":"JA Lerman","year":"2012","journal-title":"Nat Commun"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nprot.2009.203","article-title":"A protocol for generating a high-quality genome-scale metabolic reconstruction","volume":"5","author":"I Thiele","year":"2010","journal-title":"Nat Protoc"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1000312","DOI":"10.1371\/journal.pcbi.1000312","article-title":"Genome-scale reconstruction of Escherichia coli\u2019s transcriptional and translational machinery: A knowledge base, its mathematical formulation, and its functional characterization","volume":"5","author":"I Thiele","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e1006302","DOI":"10.1371\/journal.pcbi.1006302","article-title":"COBRAme: A computational framework for genome-scale models of metabolism and gene expression","volume":"14","author":"CJ Lloyd","year":"2018","journal-title":"PLOS Comput Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkw952","article-title":"BRENDA in 2017: new perspectives and new tools in BRENDA","volume":"45","author":"S Placzek","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/msb.2013.52","article-title":"Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction","volume":"9","author":"EJ O\u2019Brien","year":"2013","journal-title":"Mol Syst Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13068-014-0144-4","article-title":"Capturing the response of Clostridium acetobutylicumto chemical stressors using a regulated genome-scale metabolic model","volume":"7","author":"S Dash","year":"2014","journal-title":"Biotechnol Biofuels"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1038\/s41467-018-06993-6","article-title":"Optimization of carbon and energy utilization through differential translational efficiency","volume":"9","author":"MM Al-Bassam","year":"2018","journal-title":"Nat Commun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"12800","DOI":"10.1038\/ncomms12800","article-title":"CO2 fixation by anaerobic non-photosynthetic mixotrophy for improved carbon conversion","volume":"7","author":"SW Jones","year":"2016","journal-title":"Nat Commun"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s10295-010-0794-6","article-title":"Effect of trace metals on ethanol production from synthesis gas by the ethanologenic acetogen, <italic>Clostridium ragsdalei<\/italic>","volume":"38","author":"J Saxena","year":"2011","journal-title":"J Ind Microbiol Biotechnol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.1128\/AEM.00880-08","article-title":"Aerobic fermentation of D-glucose by an evolved cytochrome oxidase-deficient <italic>Escherichia coli<\/italic> strain","volume":"74","author":"VA Portnoy","year":"2008","journal-title":"Appl Environ Microbiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance analysis?","volume":"28","author":"JD Orth","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1752-0509-7-74","article-title":"COBRApy: COnstraints-Based Reconstruction and Analysis for Python","volume":"7","author":"A Ebrahim","year":"2013","journal-title":"BMC Syst Biol"},{"key":"ref36","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":"ref37","doi-asserted-by":"crossref","first-page":"D471","DOI":"10.1093\/nar\/gkv1164","article-title":"The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway\/genome databases","volume":"44","author":"R Caspi","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4161\/rna.8.1.13346","article-title":"ARNold: A web tool for the prediction of Rho-independent transcription terminators","volume":"8","author":"M Naville","year":"2011","journal-title":"RNA Biol"},{"key":"ref39","article-title":"tRNAscan-SE On-line: integrating search and context for analysis of transfer RNA genes","volume":"W54\u2013W57","author":"TM Lowe","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"D158","DOI":"10.1093\/nar\/gkw1099","article-title":"UniProt: the universal protein knowledgebase","volume":"45","author":"U Consortium","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"ref41","unstructured":"Wunderling R. Paralleler und Objektorientierter Simplex. 1996; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/opus4.kobv.de\/opus4-zib\/frontdoor\/index\/index\/docId\/538\" xlink:type=\"simple\">https:\/\/opus4.kobv.de\/opus4-zib\/frontdoor\/index\/index\/docId\/538<\/ext-link>"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"JD Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1109\/MCSE.2007.53","article-title":"IPython: A system for interactive scientific computing Python","volume":"9","author":"F P\u00e9rez","year":"2007","journal-title":"Comput Sci Eng"},{"key":"ref44","unstructured":"Seabold S, Perktold J. Statsmodels: Econometric and statistical modeling with Python. PROC 9th PYTHON Sci CONF. 2010; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/conference.scipy.org\/proceedings\/scipy2010\/pdfs\/seabold.pdf\" xlink:type=\"simple\">http:\/\/conference.scipy.org\/proceedings\/scipy2010\/pdfs\/seabold.pdf<\/ext-link>"},{"key":"ref45","unstructured":"Jones E, Oliphant T, Peterson P. SciPy: Open source scientific tools for Python. 2001; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.scipy.org\/\" xlink:type=\"simple\">https:\/\/www.scipy.org\/<\/ext-link>"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1006848","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T00:00:00Z","timestamp":1553212800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006848","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T19:55:16Z","timestamp":1588967716000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006848"}},"subtitle":[],"editor":[{"given":"Christopher","family":"Henry","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1006848","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1006848","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]}}}