{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:21:28Z","timestamp":1772166088641,"version":"3.50.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U01GM102098"],"award-info":[{"award-number":["U01GM102098"]}],"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":["R01GM057089"],"award-info":[{"award-number":["R01GM057089"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12918-018-0675-6","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T06:55:10Z","timestamp":1547016910000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["DynamicME: dynamic simulation and refinement of integrated models of metabolism and protein expression"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6663-7643","authenticated-orcid":false,"given":"Laurence","family":"Yang","sequence":"first","affiliation":[]},{"given":"Ali","family":"Ebrahim","sequence":"additional","affiliation":[]},{"given":"Colton J.","family":"Lloyd","sequence":"additional","affiliation":[]},{"given":"Michael A.","family":"Saunders","sequence":"additional","affiliation":[]},{"given":"Bernhard O.","family":"Palsson","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,1,9]]},"reference":[{"issue":"1","key":"675_CR1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1146\/annurev.mi.03.100149.002103","volume":"3","author":"J Monod","year":"1949","unstructured":"Monod J. The growth of bacterial cultures. Ann Rev Microbiol. 1949; 3(1):371\u201394.","journal-title":"Ann Rev Microbiol"},{"issue":"7","key":"675_CR2","doi-asserted-by":"publisher","first-page":"1006302","DOI":"10.1371\/journal.pcbi.1006302","volume":"14","author":"CJ Lloyd","year":"2018","unstructured":"Lloyd CJ, Ebrahim A, Yang L, King ZA, Catoiu E, O\u2019Brien EJ, Liu JK, Palsson BO. COBRAme: A computational framework for genome-scale models of metabolism and gene expression. PLoS Comput Biol. 2018; 14(7):1006302.","journal-title":"PLoS Comput Biol"},{"key":"675_CR3","doi-asserted-by":"publisher","first-page":"1000312","DOI":"10.1371\/journal.pcbi.1000312","volume":"5","author":"I Thiele","year":"2009","unstructured":"Thiele I, Jamshidi N, Fleming RM, Palsson B\u00d8. Genome-scale reconstruction of escherichia coli\u2019s transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization. PLoS Comput Biol. 2009; 5:1000312.","journal-title":"PLoS Comput Biol"},{"key":"675_CR4","doi-asserted-by":"publisher","first-page":"45635","DOI":"10.1371\/journal.pone.0045635","volume":"7","author":"I Thiele","year":"2012","unstructured":"Thiele I, Fleming RM, Que R, Bordbar A, Diep D, Palsson BO. Multiscale modeling of metabolism and macromolecular synthesis in E. coli and its application to the evolution of codon usage. PloS ONE. 2012; 7:45635.","journal-title":"PloS ONE"},{"key":"675_CR5","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.cell.2015.05.019","volume":"161","author":"EJ O\u2019Brien","year":"2015","unstructured":"O\u2019Brien EJ, Monk JM, Palsson BO. Using genome-scale models to predict biological capabilities. Cell. 2015; 161:971\u201387.","journal-title":"Cell"},{"key":"675_CR6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/nbt.1614","volume":"28","author":"JD Orth","year":"2010","unstructured":"Orth JD, Thiele I, Palsson BO. What is flux balance analysis?Nat Biotechnol. 2010; 28:245\u20138.","journal-title":"Nat Biotechnol"},{"key":"675_CR7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nrg3643","volume":"15","author":"A Bordbar","year":"2014","unstructured":"Bordbar A, Monk JM, King ZA, Palsson BO. Constraint-based models predict metabolic and associated cellular functions. Nat Rev Genet. 2014; 15:107\u201320.","journal-title":"Nat Rev Genet"},{"key":"675_CR8","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nrmicro2737","volume":"10","author":"NE Lewis","year":"2012","unstructured":"Lewis NE, Nagarajan H, Palsson BO. Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods. Nat Rev Microbiol. 2012; 10:291\u2013305.","journal-title":"Nat Rev Microbiol"},{"key":"675_CR9","doi-asserted-by":"publisher","first-page":"12663","DOI":"10.1073\/pnas.0609845104","volume":"104","author":"QK Beg","year":"2007","unstructured":"Beg QK, Vazquez A, Ernst J, de Menezes MA, Bar-Joseph Z, Barabasi A-L, Oltvai ZN. Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity. Proc Natl Acad Sci USA. 2007; 104:12663\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"675_CR10","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/ncomms1928","volume":"3","author":"JA Lerman","year":"2012","unstructured":"Lerman JA, Hyduke DR, Latif H, Portnoy VA, Lewis NE, Orth JD, Schrimpe-Rutledge AC, Smith RD, Adkins JN, Zengler K, et al. In silico method for modelling metabolism and gene product expression at genome scale. Nat Commun. 2012; 3:929.","journal-title":"Nat Commun"},{"key":"675_CR11","first-page":"1","volume":"9","author":"EJ O\u2019Brien","year":"2013","unstructured":"O\u2019Brien EJ, Lerman JA, Chang RL, Hyduke DR, Palsson BO. Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction. Mol Syst Biol. 2013; 9:1.","journal-title":"Mol Syst Biol"},{"key":"675_CR12","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12918-014-0110-6","volume":"8","author":"JK Liu","year":"2014","unstructured":"Liu JK, O\u2019Brien EJ, Lerman JA, Zengler K, Palsson BO, Feist AM. Reconstruction and modeling protein translocation and compartmentalization in Escherichia coli at the genome-scale. BMC Syst Biol. 2014; 8:110.","journal-title":"BMC Syst Biol"},{"key":"675_CR13","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.mib.2018.01.002","volume":"45","author":"L Yang","year":"2018","unstructured":"Yang L, Yurkovich JT, King ZA, Palsson BO. Modeling the multi-scale mechanisms of macromolecular resource allocation. Curr Opin Microbiol. 2018; 45:8\u201315.","journal-title":"Curr Opin Microbiol"},{"key":"675_CR14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.copbio.2014.12.017","volume":"34","author":"EJ O\u2019Brien","year":"2015","unstructured":"O\u2019Brien EJ, Palsson BO. Computing the functional proteome: recent progress and future prospects for genome-scale models. Curr Opin Biotechnol. 2015; 34:125\u201334.","journal-title":"Curr Opin Biotechnol"},{"key":"675_CR15","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1128\/AEM.60.10.3724-3731.1994","volume":"60","author":"A Varma","year":"1994","unstructured":"Varma A, Palsson BO. Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl Environ Microbiol. 1994; 60:3724\u201331.","journal-title":"Appl Environ Microbiol"},{"key":"675_CR16","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0006-3495(02)73903-9","volume":"83","author":"R Mahadevan","year":"2002","unstructured":"Mahadevan R, Edwards JS, Doyle FJ. Dynamic flux balance analysis of diauxic growth in Escherichia coli. Biophys J. 2002; 83:1331\u201340.","journal-title":"Biophys J"},{"key":"675_CR17","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1006\/jtbi.2001.2405","volume":"213","author":"MW Covert","year":"2001","unstructured":"Covert MW, Schilling CH, Palsson B. Regulation of gene expression in flux balance models of metabolism. J Theor Biol. 2001; 213:73\u201388.","journal-title":"J Theor Biol"},{"key":"675_CR18","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.ymben.2008.06.004","volume":"10","author":"N Anesiadis","year":"2008","unstructured":"Anesiadis N, Cluett WR, Mahadevan R. Dynamic metabolic engineering for increasing bioprocess productivity. Metab Eng. 2008; 10:255\u201366.","journal-title":"Metab Eng"},{"issue":"1","key":"675_CR19","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1472-6750-13-8","volume":"13","author":"K Zhuang","year":"2013","unstructured":"Zhuang K, Yang L, Cluett WR, Mahadevan R. Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and productivity. dyssco strategy for strain design. BMC Biotechnol. 2013; 13(1):8.","journal-title":"BMC Biotechnol"},{"key":"675_CR20","doi-asserted-by":"publisher","first-page":"15247","DOI":"10.1038\/srep15247","volume":"5","author":"M R\u00fcgen","year":"2015","unstructured":"R\u00fcgen M, Bockmayr A, Steuer R. Elucidating temporal resource allocation and diurnal dynamics in phototrophic metabolism using conditional FBA. Sci Rep. 2015; 5:15247.","journal-title":"Sci Rep"},{"key":"675_CR21","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.jtbi.2014.10.035","volume":"365","author":"S Waldherr","year":"2015","unstructured":"Waldherr S, Oyarz\u00fan DA, Bockmayr A. Dynamic optimization of metabolic networks coupled with gene expression. J Theor Biol. 2015; 365:469\u201385.","journal-title":"J Theor Biol"},{"issue":"1","key":"675_CR22","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1186\/s12859-016-1240-1","volume":"17","author":"L Yang","year":"2016","unstructured":"Yang L, Ma D, Ebrahim A, Lloyd CJ, Saunders MA, Palsson BO. solveME: fast and reliable solution of nonlinear ME models. BMC Bioinform. 2016; 17(1):391.","journal-title":"BMC Bioinform"},{"key":"675_CR23","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.ymben.2015.10.003","volume":"32","author":"A Goelzer","year":"2015","unstructured":"Goelzer A, Muntel J, Chubukov V, Jules M, Prestel E, N\u00f6lker R, Mariadassou M, Aymerich S, Hecker M, Noirot P, et al. Quantitative prediction of genome-wide resource allocation in bacteria. Metab Eng. 2015; 32:232\u201343.","journal-title":"Metab Eng"},{"issue":"6-7","key":"675_CR24","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s00285-017-1118-5","volume":"75","author":"L Tournier","year":"2017","unstructured":"Tournier L, Goelzer A, Fromion V. Optimal resource allocation enables mathematical exploration of microbial metabolic configurations. J Math Biol. 2017; 75(6-7):1349\u201380.","journal-title":"J Math Biol"},{"key":"675_CR25","volume-title":"Numerical Analysis and Optimization, NAO-III","author":"D Ma","year":"2015","unstructured":"Ma D, Saunders MA. Solving multiscale linear programs using the simplex method in quadruple precision In: Al-Baali M, Grandinetti L, Purnama A, editors. Numerical Analysis and Optimization, NAO-III. Cham: Springer International Publishing Switzerland: 2015. p. 223\u201335."},{"key":"675_CR26","doi-asserted-by":"publisher","first-page":"40863","DOI":"10.1038\/srep40863","volume":"7","author":"D Ma","year":"2017","unstructured":"Ma D, Yang L, Fleming RM, Thiele I, Palsson BO, Saunders MA. Reliable and efficient solution of genome-scale models of metabolism and macromolecular expression. Sci Rep. 2017; 7:40863.","journal-title":"Sci Rep"},{"key":"675_CR27","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/gb-2009-10-10-r118","volume":"10","author":"TM Conrad","year":"2009","unstructured":"Conrad TM, Joyce AR, Applebee MK, Barrett CL, Xie B, Gao Y, Palsson BO. Whole-genome resequencing of escherichia coli k-12 mg1655 undergoing short-term laboratory evolution in lactate minimal media reveals flexible selection of adaptive mutations. Genome Biol. 2009; 10:118.","journal-title":"Genome Biol"},{"key":"675_CR28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1128\/AEM.02246-14","volume":"81","author":"RA LaCroix","year":"2015","unstructured":"LaCroix RA, Sandberg TE, O\u2019Brien EJ, Utrilla J, Ebrahim A, Guzman GI, Szubin R, Palsson BO, Feist AM. Use of adaptive laboratory evolution to discover key mutations enabling rapid growth of Escherichia coli K-12 MG1655 on glucose minimal medium. Appl Environ Microbiol. 2015; 81:17\u201330.","journal-title":"Appl Environ Microbiol"},{"key":"675_CR29","doi-asserted-by":"publisher","first-page":"00410","DOI":"10.1128\/AEM.00410-17","volume":"83","author":"TE Sandberg","year":"2017","unstructured":"Sandberg TE, Lloyd CJ, Palsson BO, Feist AM. Laboratory evolution to alternating substrate environments yields distinct phenotypic and genetic adaptive strategies. Appl Environ Microbiol. 2017; 83:00410\u201317.","journal-title":"Appl Environ Microbiol"},{"key":"675_CR30","doi-asserted-by":"publisher","first-page":"23150","DOI":"10.1074\/jbc.M110.195305","volume":"286","author":"MK Applebee","year":"2011","unstructured":"Applebee MK, Joyce AR, Conrad TM, Pettigrew DW, Palsson B\u00d8. Functional and metabolic effects of adaptive glycerol kinase (GLPK) mutants in Escherichia coli. Journal of Biological Chemistry. 2011; 286:23150\u201323159.","journal-title":"Journal of Biological Chemistry"},{"key":"675_CR31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature15765","volume":"528","author":"M Basan","year":"2015","unstructured":"Basan M, Hui S, Okano H, Zhang Z, Shen Y, Williamson JR, Hwa T. Overflow metabolism in Escherichia coli results from efficient proteome allocation. Nature. 2015; 528:99\u2013104.","journal-title":"Nature"},{"key":"675_CR32","doi-asserted-by":"publisher","first-page":"1004998","DOI":"10.1371\/journal.pcbi.1004998","volume":"12","author":"E O\u2019Brien","year":"2016","unstructured":"O\u2019Brien E, Utrilla J, Palsson B. Quantification and classification of E. coli proteome utilization and unused protein costs across environments. PLoS Comput Biol. 2016; 12:1004998.","journal-title":"PLoS Comput Biol"},{"key":"675_CR33","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1080\/00401706.1994.10485840","volume":"36","author":"A Cutler","year":"1994","unstructured":"Cutler A, Breiman L. Archetypal analysis. Technometrics. 1994; 36:338\u201347.","journal-title":"Technometrics"},{"issue":"3","key":"675_CR34","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1080\/00401706.2016.1247017","volume":"59","author":"A Damle","year":"2017","unstructured":"Damle A, Sun Y. A geometric approach to archetypal analysis and nonnegative matrix factorization. Technometrics. 2017; 59(3):361\u201370.","journal-title":"Technometrics"},{"key":"675_CR35","volume-title":"CVPR 2014 - IEEE Conference on Computer Vision & Pattern Recognition","author":"Y Chen","year":"2014","unstructured":"Chen Y, Mairal J, Harchaoui Z. Fast and robust archetypal analysis for representation learning. In: CVPR 2014 - IEEE Conference on Computer Vision & Pattern Recognition. Piscataway: IEEE: 2014."},{"key":"675_CR36","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nmeth.3254","volume":"12","author":"Y Hart","year":"2015","unstructured":"Hart Y, Sheftel H, Hausser J, Szekely P, Ben-Moshe NB, Korem Y, Tendler A, Mayo AE, Alon U. Inferring biological tasks using Pareto analysis of high-dimensional data. Nat Methods. 2015; 12:233\u20135.","journal-title":"Nat Methods"},{"issue":"1","key":"675_CR37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1057\/palgrave.jors.2601443","volume":"54","author":"CD Tarantilis","year":"2003","unstructured":"Tarantilis CD, Kiranoudis CT, Vassiliadis VS. A list based threshold accepting metaheuristic for the heterogeneous fixed fleet vehicle routing problem. J Oper Res Soc. 2003; 54(1):65\u201371.","journal-title":"J Oper Res Soc"},{"key":"675_CR38","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.advwatres.2011.04.013","volume":"34","author":"LD Dalcin","year":"2011","unstructured":"Dalcin LD, Paz RR, Kler PA, Cosimo A. Parallel distributed computing using python. Adv Water Res. 2011; 34:1124\u201339.","journal-title":"Adv Water Res"},{"key":"675_CR39","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1038\/ng.281","volume":"40","author":"MJ Dunlop","year":"2008","unstructured":"Dunlop MJ, Cox RS, Levine JH, Murray RM, Elowitz MB. Regulatory activity revealed by dynamic correlations in gene expression noise. Nat Genet. 2008; 40:1493\u20138.","journal-title":"Nat Genet"},{"key":"675_CR40","unstructured":"R Core Team: R: A Language and Environment for Statistical Computing. Vienna; 2016. R Foundation for Statistical Computing, \n                    https:\/\/www.R-project.org\/\n                    \n                  . Accessed 14 Nov 2018."},{"key":"675_CR41","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/bit.20542","volume":"91","author":"SS Fong","year":"2005","unstructured":"Fong SS, Burgard AP, Herring CD, Knight EM, Blattner FR, Maranas CD, Palsson BO. In silico design and adaptive evolution of Escherichia coli for production of lactic acid. Biotechnol Bioeng. 2005; 91:643\u20138.","journal-title":"Biotechnol Bioeng"},{"key":"675_CR42","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/bit.21073","volume":"95","author":"Q Hua","year":"2006","unstructured":"Hua Q, Joyce AR, Fong SS, Palsson BO. Metabolic analysis of adaptive evolution for in silico-designed lactate-producing strains. Biotechnol Bioeng. 2006; 95:992\u20131002.","journal-title":"Biotechnol Bioeng"},{"key":"675_CR43","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1093\/molbev\/msu209","volume":"31","author":"TE Sandberg","year":"2014","unstructured":"Sandberg TE, Pedersen M, LaCroix RA, Ebrahim A, Bonde M, Herrgard MJ, Palsson BO, Sommer M, Feist AM. Evolution of Escherichia coli to 42 \u2218C and subsequent genetic engineering reveals adaptive mechanisms and novel mutations. Mol Biol Evol. 2014; 31:2647\u201362.","journal-title":"Mol Biol Evol"},{"key":"675_CR44","doi-asserted-by":"publisher","first-page":"13091","DOI":"10.1038\/ncomms13091","volume":"7","author":"A Ebrahim","year":"2016","unstructured":"Ebrahim A, Brunk E, Tan J, O\u2019Brien EJ, Kim D, Szubin R, Lerman JA, Lechner A, Sastry A, Bordbar A, Feist AM, Palsson BO. Multi-omic data integration enables discovery of hidden biological regularities. Nat Commun. 2016; 7:13091.","journal-title":"Nat Commun"},{"key":"675_CR45","doi-asserted-by":"publisher","first-page":"10810","DOI":"10.1073\/pnas.1501384112","volume":"112","author":"L Yang","year":"2015","unstructured":"Yang L, Tan J, O\u2019Brien E, Monk J, Kim D, Li H, Charusanti P, Ebrahim A, Lloyd C, Yurkovich J, Du B, Dr\u00e4ger A, Thomas A, Sun Y, Saunders M, Palsson B. A systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data. Proc Natl Acad Sci USA. 2015; 112:10810\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"675_CR46","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1126\/science.277.5330.1275","volume":"277","author":"A Arkin","year":"1997","unstructured":"Arkin A, Shen P, Ross J. A test case of correlation metric construction of a reaction pathway from measurements. Science. 1997; 277:1275\u20139.","journal-title":"Science"},{"issue":"1","key":"675_CR47","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/nar\/28.1.33","volume":"28","author":"RL Tatusov","year":"2000","unstructured":"Tatusov RL, Galperin MY, Natale DA, Koonin EV. The cog database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res. 2000; 28(1):33\u201336.","journal-title":"Nucleic Acids Res"},{"issue":"51","key":"675_CR48","doi-asserted-by":"publisher","first-page":"20527","DOI":"10.1073\/pnas.1309356110","volume":"110","author":"MY Pavlov","year":"2013","unstructured":"Pavlov MY, Ehrenberg M. Optimal control of gene expression for fast proteome adaptation to environmental change. Proc Natl Acad Sci USA. 2013; 110(51):20527\u201332.","journal-title":"Proc Natl Acad Sci USA"},{"key":"675_CR49","doi-asserted-by":"publisher","first-page":"36734","DOI":"10.1038\/srep36734","volume":"6","author":"L Yang","year":"2016","unstructured":"Yang L, Yurkovich JT, Lloyd CJ, Ebrahim A, Saunders MA, Palsson BO. Principles of proteome allocation are revealed using proteomic data and genome-scale models. Sci Rep. 2016; 6:36734.","journal-title":"Sci Rep"},{"key":"675_CR50","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1093\/nar\/gkw1003","volume":"45","author":"IM Keseler","year":"2017","unstructured":"Keseler IM, Mackie A, Santos-Zavaleta A, Billington R, Bonavides-Mart\u00ednez C, Caspi R, Fulcher C, Gama-Castro S, Kothari A, Krummenacker M, et al. The ecocyc database: reflecting new knowledge about escherichia coli k-12. Nucleic Acids Res. 2017; 45:543\u201350.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"675_CR51","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrg3185","volume":"13","author":"C Vogel","year":"2012","unstructured":"Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012; 13(4):227.","journal-title":"Nat Rev Genet"},{"key":"675_CR52","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/1471-2105-14-240","volume":"14","author":"Y Sun","year":"2013","unstructured":"Sun Y, Fleming RM, Thiele I, Saunders MA. Robust flux balance analysis of multiscale biochemical reaction networks. BMC Bioinformatics. 2013; 14:240.","journal-title":"BMC Bioinformatics"},{"key":"675_CR53","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/bit.22844","volume":"107","author":"JD Orth","year":"2010","unstructured":"Orth JD, Palsson BO. Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng. 2010; 107:403\u2013412.","journal-title":"Biotechnol Bioeng"},{"issue":"10","key":"675_CR54","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.bbagen.2011.05.014","volume":"1810","author":"A Goelzer","year":"2011","unstructured":"Goelzer A, Fromion V. Bacterial growth rate reflects a bottleneck in resource allocation. Biochim Biophys Acta (BBA) Gen Subj. 2011; 1810(10):978\u201388.","journal-title":"Biochim Biophys Acta (BBA) Gen Subj"},{"issue":"4","key":"675_CR55","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1042\/BST20160436","volume":"45","author":"A Goelzer","year":"2017","unstructured":"Goelzer A, Fromion V. Resource allocation in living organisms. Biochem Soc Trans. 2017; 45(4):945\u201352.","journal-title":"Biochem Soc Trans"},{"issue":"19","key":"675_CR56","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ifacol.2018.09.020","volume":"51","author":"G Jeanne","year":"2018","unstructured":"Jeanne G, Goelzer A, Tebbani S, Dumur D, Fromion V. Dynamical resource allocation models for bioreactor optimization. IFAC-PapersOnLine. 2018; 51(19):20\u201323.","journal-title":"IFAC-PapersOnLine"},{"issue":"43","key":"675_CR57","doi-asserted-by":"publisher","first-page":"11548","DOI":"10.1073\/pnas.1705524114","volume":"114","author":"K Chen","year":"2017","unstructured":"Chen K, Gao Y, Mih N, O\u2019Brien EJ, Yang L, Palsson BO. Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation. Proc Natl Acad Sci USA. 2017; 114(43):11548\u201311553.","journal-title":"Proc Natl Acad Sci USA"},{"key":"675_CR58","doi-asserted-by":"publisher","unstructured":"Yang L, Mih N, Anand A, Park JH, Tan J, Yurkovich JT, Monk JM, Lloyd CJ, Sandberg TE, Seo SW, Kim D, Sastry AV, Phaneuf P, Gao Y, Broddrick JT, Chen K, Heckmann D, Szubin R, Hefner Y, Feist AM, Palsson BO. Cellular responses to reactive oxygen species can be predicted on multiple biological scales from molecular mechanisms. bioRxiv. 227892. 2018. \n                    https:\/\/doi.org\/10.1101\/227892\n                    \n                  .","DOI":"10.1101\/227892"},{"issue":"9","key":"675_CR59","doi-asserted-by":"publisher","first-page":"882","DOI":"10.15252\/msb.20166998","volume":"12","author":"JL Radzikowski","year":"2016","unstructured":"Radzikowski JL, Vedelaar S, Siegel D, Ortega \u00c1D, Schmidt A, Heinemann M. Bacterial persistence is an active \u03c3s stress response to metabolic flux limitation. Mol Syst Biol. 2016; 12(9):882.","journal-title":"Mol Syst Biol"},{"key":"675_CR60","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.copbio.2014.12.016","volume":"35","author":"ZA King","year":"2015","unstructured":"King ZA, Lloyd CJ, Feist AM, Palsson BO. Next-generation genome-scale models for metabolic engineering. Curr Opin Biotechnol. 2015; 35:23\u201329.","journal-title":"Curr Opin Biotechnol"},{"key":"675_CR61","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.ymben.2014.11.013","volume":"28","author":"L Yang","year":"2015","unstructured":"Yang L, Srinivasan S, Mahadevan R, Cluett WR. Characterizing metabolic pathway diversification in the context of perturbation size. Metab Eng. 2015; 28:114\u201322.","journal-title":"Metab Eng"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12918-018-0675-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12918-018-0675-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12918-018-0675-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T06:54:44Z","timestamp":1589525684000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/s12918-018-0675-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,9]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["675"],"URL":"https:\/\/doi.org\/10.1186\/s12918-018-0675-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/319962","asserted-by":"object"}]},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,9]]},"assertion":[{"value":"14 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"2"}}