{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:59:11Z","timestamp":1768705151587,"version":"3.49.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. <jats:italic>Clostridium thermocellum<\/jats:italic> (ATCC 27405) is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major challenge in using microorganisms for chemical production is the need to modify the organism to increase production efficiency. The process of properly engineering an organism is typically arduous.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here we present a genome-scale model of <jats:italic>C. thermocellum<\/jats:italic> metabolism, <jats:italic>i<\/jats:italic> SR432, for the purpose of establishing a computational tool to study the metabolic network of <jats:italic>C. thermocellum<\/jats:italic> and facilitate efforts to engineer <jats:italic>C. thermocellum<\/jats:italic> for biofuel production. The model consists of 577 reactions involving 525 intracellular metabolites, 432 genes, and a proteomic-based representation of a cellulosome. The process of constructing this metabolic model led to suggested annotation refinements for 27 genes and identification of areas of metabolism requiring further study. The accuracy of the <jats:italic>i<\/jats:italic> SR432 model was tested using experimental growth and by-product secretion data for growth on cellobiose and fructose. Analysis using this model captures the relationship between the reduction-oxidation state of the cell and ethanol secretion and allowed for prediction of gene deletions and environmental conditions that would increase ethanol production.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>By incorporating genomic sequence data, network topology, and experimental measurements of enzyme activities and metabolite fluxes, we have generated a model that is reasonably accurate at predicting the cellular phenotype of <jats:italic>C. thermocellum<\/jats:italic> and establish a strong foundation for rational strain design. In addition, we are able to draw some important conclusions regarding the underlying metabolic mechanisms for observed behaviors of <jats:italic>C. thermocellum<\/jats:italic> and highlight remaining gaps in the existing genome annotations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-31","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T07:16:40Z","timestamp":1269328600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Genome-scale metabolic analysis of Clostridium thermocellum for bioethanol production"],"prefix":"10.1186","volume":"4","author":[{"given":"Seth B","family":"Roberts","sequence":"first","affiliation":[]},{"given":"Christopher M","family":"Gowen","sequence":"additional","affiliation":[]},{"given":"J Paul","family":"Brooks","sequence":"additional","affiliation":[]},{"given":"Stephen S","family":"Fong","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"420_CR1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/msb.2008.15","volume":"4","author":"AK Chavali","year":"2008","unstructured":"Chavali AK, Whittemore JD, Eddy JA, Williams KT, Papin JA: Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major. Mol Syst Biol. 2008, 4: 177- 10.1038\/msb.2008.15","journal-title":"Mol Syst Biol"},{"issue":"39","key":"420_CR2","doi-asserted-by":"publisher","first-page":"28791","DOI":"10.1074\/jbc.M703759200","volume":"282","author":"Y Oh","year":"2007","unstructured":"Oh Y, Palsson BO, Park SM, Schilling CH, Mahadevan R: Genome-scale Reconstruction of Metabolic Network in Bacillus subtilis Based on High-throughput Phenotyping and Gene Essentiality Data. J Biol Chem. 2007, 282 (39): 28791-28799. 10.1074\/jbc.M703759200","journal-title":"J Biol Chem"},{"issue":"7","key":"420_CR3","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1101\/gr.2250904","volume":"14","author":"NC Duarte","year":"2004","unstructured":"Duarte NC, Herrgard MJ, Palsson BO: Reconstruction and Validation of Saccharomyces cerevisiae iND750, a Fully Compartmentalized Genome-Scale Metabolic Model. Genome Res. 2004, 14 (7): 1298-1309. 10.1101\/gr.2250904","journal-title":"Genome Res"},{"issue":"3","key":"420_CR4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1046\/j.1462-2920.2002.00282.x","volume":"4","author":"JS Edwards","year":"2002","unstructured":"Edwards JS, Covert M, Palsson B: Metabolic modelling of microbes: the flux-balance approach. Environ Microbiol. 2002, 4 (3): 133-140. 10.1046\/j.1462-2920.2002.00282.x","journal-title":"Environ Microbiol"},{"issue":"3","key":"420_CR5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.jtbi.2004.01.008","volume":"228","author":"DA Beard","year":"2004","unstructured":"Beard DA, Babson E, Curtis E, Qian H: Thermodynamic constraints for biochemical networks. J Theor Biol. 2004, 228 (3): 327-333. 10.1016\/j.jtbi.2004.01.008","journal-title":"J Theor Biol"},{"issue":"4","key":"420_CR6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.ymben.2005.03.002","volume":"7","author":"F Yang","year":"2005","unstructured":"Yang F, Qian H, Beard DA: Ab initio prediction of thermodynamically feasible reaction directions from biochemical network stoichiometry. Metab Eng. 2005, 7 (4): 251-259. 10.1016\/j.ymben.2005.03.002","journal-title":"Metab Eng"},{"issue":"10","key":"420_CR7","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/nbt1094-994","volume":"12","author":"A Varma","year":"1994","unstructured":"Varma A, Palsson BO: Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use. Nat Biotech. 1994, 12 (10): 994-998. 10.1038\/nbt1094-994.","journal-title":"Nat Biotech"},{"issue":"3","key":"420_CR8","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nbt0302-243","volume":"20","author":"M Cascante","year":"2002","unstructured":"Cascante M, Boros LG, Comin-Anduix B, de Atauri P, Centelles JJ, Lee PW-: Metabolic control analysis in drug discovery and disease. Nat Biotech. 2002, 20 (3): 243-249. 10.1038\/nbt0302-243.","journal-title":"Nat Biotech"},{"issue":"18","key":"420_CR9","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1093\/bioinformatics\/btm374","volume":"23","author":"J Yoon","year":"2007","unstructured":"Yoon J, Si Y, Nolan R, Lee K: Modular decomposition of metabolic reaction networks based on flux analysis and pathway projection. Bioinformatics. 2007, 23 (18): 2433-2440. 10.1093\/bioinformatics\/btm374","journal-title":"Bioinformatics"},{"issue":"2","key":"420_CR10","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/84379","volume":"19","author":"JS Edwards","year":"2001","unstructured":"Edwards JS, Ibarra RU, Palsson BO: In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol. 2001, 19 (2): 125-130. 10.1038\/84379","journal-title":"Nat Biotechnol"},{"issue":"10","key":"420_CR11","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/ng1432","volume":"36","author":"SS Fong","year":"2004","unstructured":"Fong SS, Palsson BO: Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes. Nat Genet. 2004, 36 (10): 1056-1058. 10.1038\/ng1432","journal-title":"Nat Genet"},{"issue":"5","key":"420_CR12","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 (5): 992-1002. 10.1002\/bit.21073","journal-title":"Biotechnol Bioeng"},{"issue":"11","key":"420_CR13","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1101\/gr.6678707","volume":"17","author":"T Shlomi","year":"2007","unstructured":"Shlomi T, Herrgard M, Portnoy V, Naim E, Palsson B\u00d8, Sharan R, Ruppin E: Systematic condition-dependent annotation of metabolic genes. Genome Res. 2007, 17 (11): 1626-1633. 10.1101\/gr.6678707","journal-title":"Genome Res"},{"issue":"2","key":"420_CR14","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nbt0208-169","volume":"26","author":"LR Lynd","year":"2008","unstructured":"Lynd LR, Laser MS, Bransby D, Dale BE, Davison B, Hamilton R, Himmel M, Keller M, McMillan JD, Sheehan J, Wyman CE: How biotech can transform biofuels. Nat Biotech. 2008, 26 (2): 169-172. 10.1038\/nbt0208-169.","journal-title":"Nat Biotech"},{"issue":"5760","key":"420_CR15","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1126\/science.1121416","volume":"311","author":"AE Farrell","year":"2006","unstructured":"Farrell AE, Plevin RJ, Turner BT, Jones AD, O'Hare M, Kammen DM: Ethanol Can Contribute to Energy and Environmental Goals. Science. 2006, 311 (5760): 506-508. 10.1126\/science.1121416","journal-title":"Science"},{"issue":"6","key":"420_CR16","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1021\/es052024h","volume":"40","author":"R Hammerschlag","year":"2006","unstructured":"Hammerschlag R: Ethanol's Energy Return on Investment: A Survey of the Literature 1990-Present. Environ Sci Technol. 2006, 40 (6): 1744-1750. 10.1021\/es052024h","journal-title":"Environ Sci Technol"},{"issue":"5813","key":"420_CR17","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1126\/science.1139612","volume":"315","author":"G Stephanopoulos","year":"2007","unstructured":"Stephanopoulos G: Challenges in Engineering Microbes for Biofuels Production. Science. 2007, 315 (5813): 801-804. 10.1126\/science.1139612","journal-title":"Science"},{"issue":"5","key":"420_CR18","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.copbio.2005.08.009","volume":"16","author":"LR Lynd","year":"2005","unstructured":"Lynd LR, Zyl WHv, McBride JE, Laser M: Consolidated bioprocessing of cellulosic biomass: an update. Curr Opin Biotechnol. 2005, 16 (5): 577-583. 10.1016\/j.copbio.2005.08.009","journal-title":"Curr Opin Biotechnol"},{"issue":"5","key":"420_CR19","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1002\/bit.22009","volume":"101","author":"RS Senger","year":"2008","unstructured":"Senger RS, Papoutsakis ET: Genome-scale model for Clostridium acetobutylicum: Part II. Development of specific proton flux states and numerically determined sub-systems. Biotechnol Bioeng. 2008, 101 (5): 1053-1071. 10.1002\/bit.22009","journal-title":"Biotechnol Bioeng"},{"issue":"5","key":"420_CR20","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/bit.22010","volume":"101","author":"RS Senger","year":"2008","unstructured":"Senger RS, Papoutsakis ET: Genome-scale model for Clostridium acetobutylicum: Part I. Metabolic network resolution and analysis. Biotechnol Bioeng. 2008, 101 (5): 1036-1052. 10.1002\/bit.22010","journal-title":"Biotechnol Bioeng"},{"issue":"5","key":"420_CR21","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1007\/s00253-008-1654-4","volume":"80","author":"J Lee","year":"2008","unstructured":"Lee J, Yun H, Feist A, Palsson B, Lee S: Genome-scale reconstruction and in silico analysis of the Clostridium acetobutylicum ATCC 824 metabolic network. Appl Microbiol Biotechnol. 2008, 80 (5): 849-862. 10.1007\/s00253-008-1654-4","journal-title":"Appl Microbiol Biotechnol"},{"issue":"5","key":"420_CR22","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 (5): 643-648. 10.1002\/bit.20542","journal-title":"Biotechnol Bioeng"},{"key":"420_CR23","doi-asserted-by":"publisher","first-page":"D190","DOI":"10.1093\/nar\/gkm895","volume":"36","author":"The UniProt Consortium","year":"2008","unstructured":", : The Universal Protein Resource (UniProt). Nucl Acids Res. 2008, 36: D190-D195. 10.1093\/nar\/gkn141","journal-title":"Nucl Acids Res"},{"issue":"1","key":"420_CR24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S: KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucl Acids Res. 2000, 28 (1): 27-30. 10.1093\/nar\/28.1.27","journal-title":"Nucl Acids Res"},{"issue":"suppl_1","key":"420_CR25","doi-asserted-by":"publisher","first-page":"D354","DOI":"10.1093\/nar\/gkj102","volume":"34","author":"M Kanehisa","year":"2006","unstructured":"Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M: From genomics to chemical genomics: new developments in KEGG. Nucl Acids Res. 2006, 34 (suppl_1): D354-357. 10.1093\/nar\/gkj102","journal-title":"Nucl Acids Res"},{"issue":"suppl_1","key":"420_CR26","first-page":"D480","volume":"36","author":"M Kanehisa","year":"2008","unstructured":"Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S, Tokimatsu T, Yamanishi Y: KEGG for linking genomes to life and the environment. Nucl Acids Res. 2008, 36 (suppl_1): D480-484.","journal-title":"Nucl Acids Res"},{"issue":"suppl_1","key":"420_CR27","first-page":"D528","volume":"36","author":"VM Markowitz","year":"2008","unstructured":"Markowitz VM, Szeto E, Palaniappan K, Grechkin Y, Chu K, Chen IA, Dubchak I, Anderson I, Lykidis A, Mavromatis K, Ivanova NN, Kyrpides NC: The integrated microbial genomes (IMG) system in 2007: data content and analysis tool extensions. Nucl Acids Res. 2008, 36 (suppl_1): D528-533.","journal-title":"Nucl Acids Res"},{"issue":"4","key":"420_CR28","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1128\/aem.41.4.1060-1062.1981","volume":"41","author":"EA Johnson","year":"1981","unstructured":"Johnson EA, Madia A, Demain AL: Chemically Defined Minimal Medium for Growth of the Anaerobic Cellulolytic Thermophile Clostridium thermocellum. Appl Environ Microbiol. 1981, 41 (4): 1060-1062.","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"420_CR29","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1128\/jb.105.1.220-225.1971","volume":"105","author":"NJ Patni","year":"1971","unstructured":"Patni NJ, Alexander JK: Utilization of Glucose by Clostridium thermocellum: Presence of Glucokinase and Other Glycolytic Enzymes in Cell Extracts. J Bacteriol. 1971, 105 (1): 220-225.","journal-title":"J Bacteriol"},{"issue":"15","key":"420_CR30","doi-asserted-by":"publisher","first-page":"6201","DOI":"10.1016\/j.ijhydene.2009.05.112","volume":"34","author":"E Lalaurette","year":"2009","unstructured":"Lalaurette E, Thammannagowda S, Mohagheghi A, Maness P, Logan BE: Hydrogen production from cellulose in a two-stage process combining fermentation and electrohydrogenesis. Int J Hydrogen Energy. 2009, 34 (15): 6201-6210. 10.1016\/j.ijhydene.2009.05.112.","journal-title":"Int J Hydrogen Energy"},{"issue":"4","key":"420_CR31","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1128\/jb.67.4.505-506.1954","volume":"67","author":"RH McBee","year":"1954","unstructured":"McBee RH: THE CHARACTERISTICS OF CLOSTRIDIUM THERMOCELLUM. J Bacteriol. 1954, 67 (4): 505-506.","journal-title":"J Bacteriol"},{"key":"420_CR32","volume-title":"Ph.D. thesis","author":"DAL Hogsett","year":"1995","unstructured":"Hogsett DAL: Cellulose Hydrolysis and Fermentation by Clostridium thermocellum for the Production of Ethanol. Ph.D. thesis. 1995, Dartmouth University, Thayer School of Engineering,"},{"issue":"3-4","key":"420_CR33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.jbiotec.2009.01.022","volume":"140","author":"T Rydzak","year":"2009","unstructured":"Rydzak T, Levin DB, Cicek N, Sparling R: Growth phase-dependant enzyme profile of pyruvate catabolism and end-product formation in Clostridium thermocellum ATCC 27405. J Biotechnol. 2009, 140 (3-4): 169-175. 10.1016\/j.jbiotec.2009.01.022","journal-title":"J Biotechnol"},{"issue":"9","key":"420_CR34","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1101\/gr.2546004","volume":"14","author":"JL Reed","year":"2004","unstructured":"Reed JL, Palsson B\u00d8: Genome-Scale In Silico Models of E. coli Have Multiple Equivalent Phenotypic States: Assessment of Correlated Reaction Subsets That Comprise Network States. Genome Res. 2004, 14 (9): 1797-1805. 10.1101\/gr.2546004","journal-title":"Genome Res"},{"issue":"1","key":"420_CR35","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1128\/MMBR.69.1.124-154.2005","volume":"69","author":"AL Demain","year":"2005","unstructured":"Demain AL, Newcomb M, Wu JH: Cellulase, clostridia, and ethanol. Microbiol Mol Biol Rev. 2005, 69 (1): 124-154. 10.1128\/MMBR.69.1.124-154.2005","journal-title":"Microbiol Mol Biol Rev"},{"issue":"5","key":"420_CR36","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1128\/aem.47.5.1126-1129.1984","volume":"47","author":"D Brener","year":"1984","unstructured":"Brener D, Johnson BF: Relationship Between Substrate Concentration and Fermentation Product Ratios in Clostridium thermocellum Cultures. Appl Environ Microbiol. 1984, 47 (5): 1126-1129.","journal-title":"Appl Environ Microbiol"},{"issue":"11","key":"420_CR37","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1016\/j.biortech.2006.08.033","volume":"98","author":"MS Chinn","year":"2007","unstructured":"Chinn MS, Nokes SE, Strobel HJ: Influence of process conditions on end product formation from Clostridium thermocellum 27405 in solid substrate cultivation on paper pulp sludge. Bioresour Technol. 2007, 98 (11): 2184-2193. 10.1016\/j.biortech.2006.08.033","journal-title":"Bioresour Technol"},{"issue":"3","key":"420_CR38","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1007\/s00253-006-0316-7","volume":"72","author":"R Islam","year":"2006","unstructured":"Islam R, Cicek N, Sparling R, Levin D: Effect of substrate loading on hydrogen production during anaerobic fermentation by Clostridium thermocellum 27405. Appl Microbiol Biotechnol. 2006, 72 (3): 576-583. 10.1007\/s00253-006-0316-7","journal-title":"Appl Microbiol Biotechnol"},{"issue":"5","key":"420_CR39","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1128\/aem.54.5.1216-1221.1988","volume":"54","author":"RJ Lamed","year":"1988","unstructured":"Lamed RJ, Lobos JH, Su TM: Effects of Stirring and Hydrogen on Fermentation Products of Clostridium thermocellum. Appl Environ Microbiol. 1988, 54 (5): 1216-1221.","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"420_CR40","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1021\/ac020271n","volume":"75","author":"Y Zhang","year":"2003","unstructured":"Zhang Y, Lynd LR: Quantification of Cell and Cellulase Mass Concentrations during Anaerobic Cellulose Fermentation: Development of an Enzyme-Linked Immunosorbent Assay-Based Method with Application to Clostridium thermocellum Batch Cultures. Anal Chem. 2003, 75 (2): 219-227. 10.1021\/ac020271n","journal-title":"Anal Chem"},{"issue":"7050","key":"420_CR41","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/nature03842","volume":"436","author":"E Dekel","year":"2005","unstructured":"Dekel E, Alon U: Optimality and evolutionary tuning of the expression level of a protein. Nature. 2005, 436 (7050): 588-592. 10.1038\/nature03842","journal-title":"Nature"},{"issue":"6","key":"420_CR42","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nbt1401","volume":"26","author":"AM Feist","year":"2008","unstructured":"Feist AM, Palsson BO: The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat Biotech. 2008, 26 (6): 659-667. 10.1038\/nbt1401.","journal-title":"Nat Biotech"},{"issue":"2","key":"420_CR43","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1046\/j.1432-1327.1999.00399.x","volume":"262","author":"S Rhee","year":"1999","unstructured":"Rhee S, Fuchs G: Phenylacetyl-CoA:acceptor oxidoreductase, a membrane-bound molybdenum-iron-sulfur enzyme involved in anaerobic metabolism of phenylalanine in the denitrifying bacterium Thauera aromatica. European Journal of Biochemistry. 1999, 262 (2): 507-515. 10.1046\/j.1432-1327.1999.00399.x","journal-title":"European Journal of Biochemistry"},{"issue":"2","key":"420_CR44","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/oxfordjournals.jbchem.a121937","volume":"101","author":"S Seki","year":"1987","unstructured":"Seki S, Hattori Y, Hasewega T, Haraguchi H, Ishimoto M: Studies on Nitrate Reductase of Clostridium perfringens. IV. Identification of Metals, Molybdenum Cofactor, and Iron-Sulfur Cluster. J Biochem. 1987, 101 (2): 503-509.","journal-title":"J Biochem"},{"issue":"6","key":"420_CR45","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1002\/bit.10803","volume":"84","author":"AP Burgard","year":"2003","unstructured":"Burgard AP, Pharkya P, Maranas CD: Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol Bioeng. 2003, 84 (6): 647-657. 10.1002\/bit.10803","journal-title":"Biotechnol Bioeng"},{"key":"420_CR46","volume-title":"Mol Syst Biol","author":"AM Feist","year":"2006","unstructured":"Feist AM, Scholten JC, Palsson BO, Brockman FJ, Ideker T: Modeling methanogenesis with a genome-scale metabolic reconstruction of Methanosarcina barkeri. Mol Syst Biol. 2006, 2: 2006.0004,"},{"key":"420_CR47","doi-asserted-by":"publisher","first-page":"D181","DOI":"10.1093\/nar\/gkj001","volume":"34","author":"MH Saier Jr","year":"2006","unstructured":"Saier MH, Tran CV, Barabote RD: TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucl Acids Res. 2006, 34: D181-D186. 10.1093\/nar\/gkj001","journal-title":"Nucl Acids Res"},{"issue":"3","key":"420_CR48","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1128\/jb.106.3.876-881.1971","volume":"106","author":"M Chan","year":"1971","unstructured":"Chan M, Himes RH, Akagi JM: Fatty Acid Composition of Thermophilic, Mesophilic, and Psychrophilic Clostridia. J Bacteriol. 1971, 106 (3): 876-881.","journal-title":"J Bacteriol"},{"issue":"1","key":"420_CR49","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/0005-2736(82)90487-4","volume":"693","author":"AA Herrero","year":"1982","unstructured":"Herrero AA, Gomez RF, Roberts MF: Ethanol-induced changes in the membrane lipid composition of Clostridium thermocellum. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1982, 693 (1): 195-204. 10.1016\/0005-2736(82)90487-4.","journal-title":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},{"issue":"21","key":"420_CR50","doi-asserted-by":"publisher","first-page":"6400","DOI":"10.1128\/JB.185.21.6400-6408.2003","volume":"185","author":"SS Fong","year":"2003","unstructured":"Fong SS, Marciniak JY, Palsson BO: Description and Interpretation of Adaptive Evolution of Escherichia coli K-12 MG1655 by Using a Genome-Scale In Silico Metabolic Model. J Bacteriol. 2003, 185 (21): 6400-6408. 10.1128\/JB.185.21.6400-6408.2003","journal-title":"J Bacteriol"},{"issue":"4","key":"420_CR51","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1006\/jtbi.1993.1203","volume":"165","author":"A Varma","year":"1993","unstructured":"Varma A, Palsson B: Metabolic Capabilities of Escherichia coli II. Optimal Growth Patterns. J Theor Biol. 1993, 165 (4): 503-522. 10.1006\/jtbi.1993.1203.","journal-title":"J Theor Biol"},{"issue":"6","key":"420_CR52","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1073\/pnas.0610772104","volume":"104","author":"NC Duarte","year":"2007","unstructured":"Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson B\u00d8: Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA. 2007, 104 (6): 1777-1782. 10.1073\/pnas.0610772104","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"420_CR53","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1128\/MMBR.66.3.506-577.2002","volume":"66","author":"LR Lynd","year":"2002","unstructured":"Lynd LR, Weimer PJ, van Zyl WH, Pretorius IS: Microbial cellulose utilization: fundamentals and biotechnology. Microbiol Mol Biol Rev. 2002, 66 (3): 506-577. 10.1128\/MMBR.66.3.506-577.2002","journal-title":"Microbiol Mol Biol Rev"},{"issue":"19","key":"420_CR54","doi-asserted-by":"publisher","first-page":"6787","DOI":"10.1128\/JB.00882-07","volume":"189","author":"ND Gold","year":"2007","unstructured":"Gold ND, Martin VJJ: Global View of the Clostridium thermocellum Cellulosome Revealed by Quantitative Proteomic Analysis. J Bacteriol. 2007, 189 (19): 6787-6795. 10.1128\/JB.00882-07","journal-title":"J Bacteriol"},{"issue":"9","key":"420_CR55","doi-asserted-by":"publisher","first-page":"R54","DOI":"10.1186\/gb-2003-4-9-r54","volume":"4","author":"J Reed","year":"2003","unstructured":"Reed J, Vo T, Schilling C, Palsson B: An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM\/GPR). Genome Biol. 2003, 4 (9): R54- 10.1186\/gb-2003-4-9-r54","journal-title":"Genome Biol"},{"issue":"2824","key":"420_CR56","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1126\/science.109.2824.144","volume":"109","author":"E Kun","year":"1949","unstructured":"Kun E, Abood LG: Colorimetric Estimation of Succinic Dehydrogenase by Triphenyltetrazolium Chloride. Science. 1949, 109 (2824): 144-146. 10.1126\/science.109.2824.144","journal-title":"Science"},{"issue":"3","key":"420_CR57","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/73786","volume":"18","author":"S Schuster","year":"2000","unstructured":"Schuster S, Fell DA, Dandekar T: A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotech. 2000, 18 (3): 326-332. 10.1038\/73786.","journal-title":"Nat Biotech"},{"issue":"8","key":"420_CR58","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S0167-7799(97)01067-6","volume":"15","author":"HPJ Bonarius","year":"1997","unstructured":"Bonarius HPJ, Schmid G, Tramper J: Flux analysis of underdetermined metabolic networks: the quest for the missing constraints. Trends Biotechnol. 1997, 15 (8): 308-314. 10.1016\/S0167-7799(97)01067-6.","journal-title":"Trends Biotechnol"},{"issue":"10","key":"420_CR59","doi-asserted-by":"publisher","first-page":"e1000210","DOI":"10.1371\/journal.pcbi.1000210","volume":"4","author":"J Pucha\u0142ka","year":"2008","unstructured":"Pucha\u0142ka J, Oberhardt MA, Godinho M, Bielecka A, Regenhardt D, Timmis KN, Papin JA, Santos Martins dos, V\u00edtor AP: Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology. PLoS Comput Biol. 2008, 4 (10): e1000210- 10.1371\/journal.pcbi.1000210","journal-title":"PLoS Comput Biol"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-31.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T11:55:56Z","timestamp":1630497356000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,22]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["420"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-31","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,22]]},"assertion":[{"value":"9 October 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"31"}}