{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:18:15Z","timestamp":1782983895460,"version":"3.54.5"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2014,9,4]],"date-time":"2014-09-04T00:00:00Z","timestamp":1409788800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003827","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T01:53:55Z","timestamp":1409882035000},"page":"e1003827","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":55,"title":["A Peptide-Based Method for 13C Metabolic Flux Analysis in Microbial Communities"],"prefix":"10.1371","volume":"10","author":[{"given":"Amit","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Nilmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay D.","family":"Keasling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aindrila","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Petzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor Garc\u00eda","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,9,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1126\/science.1153213","article-title":"The microbial engines that drive Earth&apos;s biogeochemical cycles","volume":"320","author":"PG Falkowski","year":"2008","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nature06269","article-title":"Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite","volume":"450","author":"F Warnecke","year":"2007","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Northup DE, Lavoie KH (2001) Geomicrobiology of Caves: A Review: 199\u2013222.","DOI":"10.1080\/01490450152467750"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.watres.2007.02.030","article-title":"Advances in enhanced biological phosphorus removal: From micro to macro scale","volume":"41","author":"A Oehmen","year":"2007","journal-title":"Water Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev.micro.56.012302.161052","article-title":"Heavy metal mining using microbes","volume":"56","author":"DE Rawlings","year":"2002","journal-title":"Annu Rev Microbiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2175\/106143010X12780288628534","article-title":"Research Advances and Challenges in the Microbiology of Enhanced Biological Phosphorus RemovalA Critical Review","volume":"83","author":"SY Gebremariam","year":"2011","journal-title":"Water Environ Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nrg1709","article-title":"Metagenomics: DNA sequencing of environmental samples","volume":"6","author":"SG Tringe","year":"2005","journal-title":"Nat Rev Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"e3042","DOI":"10.1371\/journal.pone.0003042","article-title":"Detection of large numbers of novel sequences in the metatranscriptomes of complex marine microbial communities","volume":"3","author":"a Gilbert J","year":"2008","journal-title":"PLoS One"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tim.2005.12.006","article-title":"Metaproteomics: studying functional gene expression in microbial ecosystems","volume":"14","author":"P Wilmes","year":"2006","journal-title":"Trends Microbiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/mas.20191","article-title":"Advances in analysis of microbial metabolic fluxes via (13)C isotopic labeling","volume":"28","author":"YJ Tang","year":"2009","journal-title":"Mass Spectrom Rev"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/nbt1094-994","article-title":"Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use","volume":"12","author":"A Varma","year":"1994","journal-title":"Nat Biotech"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00253-008-1770-1","article-title":"Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolism","volume":"81","author":"C Trinh","year":"2009","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.tibtech.2004.06.010","article-title":"Comparison of network-based pathway analysis methods","volume":"22","author":"JA Papin","year":"2004","journal-title":"Trends Biotechnol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nchembio.580","article-title":"Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol","volume":"7","author":"H Yim","year":"2011","journal-title":"Nat Chem Biol"},{"key":"ref15","first-page":"462","article-title":"Development and validation of a flux-based stoichiometric model for enhanced biological phosphorus removal metabolism","volume":"33","author":"J Pramanik","year":"1999"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/msb4100131","article-title":"Metabolic modeling of a mutualistic microbial community","volume":"3","author":"S Stolyar","year":"2007","journal-title":"Mol Syst Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/ismej.2010.117","article-title":"Genome-scale dynamic modeling of the competition between Rhodoferax and Geobacter in anoxic subsurface environments","volume":"5","author":"K Zhuang","year":"2011","journal-title":"ISME J"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/S0006-3495(02)73903-9","article-title":"Dynamic Flux Balance Analysis of Diauxic Growth in Escherichia coli","volume":"83","author":"R Mahadevan","year":"2002","journal-title":"Biophys J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/biot.201000159","article-title":"Genome-scale metabolic modeling of a clostridial co-culture for consolidated bioprocessing","volume":"5","author":"F Salimi","year":"2010","journal-title":"Biotechnol J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e1002363","DOI":"10.1371\/journal.pcbi.1002363","article-title":"OptCom: A Multi-Level Optimization Framework for the Metabolic Modeling and Analysis of Microbial Communities","volume":"8","author":"AR Zomorrodi","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Schuetz R, Kuepfer L, Sauer U (2007) Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli. Mol Syst Biol 3. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1038\/msb4100162\" xlink:type=\"simple\">http:\/\/dx.doi.org\/10.1038\/msb4100162<\/ext-link>.","DOI":"10.1038\/msb4100162"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1555","article-title":"Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism","volume":"37","author":"E Fischer","year":"2005","journal-title":"Nat Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1126\/science.1216882","article-title":"Multidimensional Optimality of Microbial Metabolism","volume":"336","author":"R Schuetz","year":"2012","journal-title":"Sci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ymben.2007.05.005","article-title":"Metabolic flux elucidation for large-scale models using 13C labeled isotopes","volume":"9","author":"PF Suthers","year":"2007","journal-title":"Metab Eng"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/mben.2001.0187","article-title":"13C Metabolic Flux Analysis","volume":"3","author":"W Wiechert","year":"2001","journal-title":"Metab Eng"},{"key":"ref26","volume":"2","unstructured":"Sauer U (2006) Metabolic networks in motion: 13C-based flux analysis. Mol Syst Biol <volume>2<\/volume> . Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1038\/msb4100109\" xlink:type=\"simple\">http:\/\/dx.doi.org\/10.1038\/msb4100109<\/ext-link>."},{"key":"ref27","unstructured":"Toya Y, Shimizu H (n.d.) Flux analysis and metabolomics for systematic metabolic engineering of microorganisms. Biotechnol Adv. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0734975013000839\" xlink:type=\"simple\">http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0734975013000839<\/ext-link>."},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1021\/pr2002885","article-title":"Metabolic Flux Analysis and Visualization\u2020","volume":"10","author":"Y Toya","year":"2011","journal-title":"J Proteome Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"39544","DOI":"10.1074\/jbc.M110.162958","article-title":"Metabolic Flux Analysis of the Mixotrophic Metabolisms in the Green Sulfur Bacterium Chlorobaculum tepidum","volume":"285","author":"X Feng","year":"2010","journal-title":"J Biol Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1128\/AEM.02696-10","article-title":"Subpopulation-Specific Metabolic Pathway Usage in Mixed Cultures as Revealed by Reporter Protein-Based 13C Analysis","volume":"77","author":"M R\u00fchl","year":"2011","journal-title":"Appl Environ Microbiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1021\/ac071445+","article-title":"Isotopomer Distributions in Amino Acids from a Highly Expressed Protein as a Proxy for Those from Total Protein","volume":"80","author":"AS Shaikh","year":"2008","journal-title":"Anal Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.copbio.2012.10.021","article-title":"Progress toward single cell metabolomics","volume":"24","author":"SS Rubakhin","year":"2013","journal-title":"Curr Opin Biotechnol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/nrmicro2080","article-title":"Systems Biology: Functional analysis of natural microbial consortia using community proteomics","volume":"7","author":"NC VerBerkmoes","year":"2009","journal-title":"Nat Rev Micro"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/pr1010058","article-title":"UNiquant, a Program for Quantitative Proteomics Analysis Using Stable Isotope Labeling","volume":"10","author":"X Huang","year":"2010","journal-title":"J Proteome Res"},{"key":"ref35","volume":"10","unstructured":"Pan C, Fischer CR, Hyatt D, Bowen BP, Hettich RL, <etal>et al<\/etal>.. (2011) Quantitative Tracking of Isotope Flows in Proteomes of Microbial Communities. Mol Cell Proteomics <volume>10<\/volume> . Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.mcponline.org\/content\/10\/4\/M110.006049.abstract\" xlink:type=\"simple\">http:\/\/www.mcponline.org\/content\/10\/4\/M110.006049.abstract<\/ext-link>."},{"key":"ref36","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1132067","article-title":"Multiple High-Throughput Analyses Monitor the Response of E. coli to Perturbations","volume":"316","author":"N Ishii","year":"2007","journal-title":"Sci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1006\/mben.1999.0117","article-title":"Isotopomer Analysis Using GC-MS","volume":"1","author":"B Christensen","year":"1999","journal-title":"Metab Eng"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jbiotec.2006.09.004","article-title":"Determination of metabolic flux changes during fed-batch cultivation from measurements of intracellular amino acids by LC-MS\/MS","volume":"128","author":"S Iwatani","year":"2007","journal-title":"J Biotechnol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.1016\/S0021-9258(18)68590-4","article-title":"Evaluation of carbon flux and substrate selection through alternate pathways involving the citric acid cycle of the heart by 13C NMR spectroscopy","volume":"263","author":"CR Malloy","year":"1988","journal-title":"J Biol Chem"},{"key":"ref40"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ymben.2006.09.001","article-title":"Elementary metabolite units (EMU): A novel framework for modeling isotopic distributions","volume":"9","author":"MR Antoniewicz","year":"2007","journal-title":"Metab Eng"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ymben.2009.10.002","article-title":"Improved computational performance of MFA using elementary metabolite units and flux coupling","volume":"12","author":"PF Suthers","year":"2010","journal-title":"Metab Eng"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/bit.10909","article-title":"New tools for mass isotopomer data evaluation in 13C flux analysis: Mass isotope correction, data consistency checking, and precursor relationships","volume":"85","author":"SA Wahl","year":"2004","journal-title":"Biotechnol Bioeng"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/btpr.420","article-title":"13C-metabolic flux analysis for batch culture of Escherichia coli and its pyk and pgi gene knockout mutants based on mass isotopomer distribution of intracellular metabolites","volume":"26","author":"Y Toya","year":"2010","journal-title":"Biotechnol Prog"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/mben.2001.0188","article-title":"A Universal Framework for 13C Metabolic Flux Analysis","volume":"3","author":"W Wiechert","year":"2001","journal-title":"Metab Eng"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.soilbio.2011.05.001","article-title":"Modeling soil metabolic processes using isotopologue pairs of position-specific 13C-labeled glucose and pyruvate","volume":"43","author":"P Dijkstra","year":"2011","journal-title":"Soil Biol Biochem"},{"key":"ref47","unstructured":"Arfken G (1985) Mathematical Methods for Physicists Academic Press. pp. 810\u2013814."},{"key":"ref48","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/bit.20011","article-title":"Using metabolic flux data to further constrain the metabolic solution space and predict internal flux patterns: the Escherichia coli spectrum","volume":"86","author":"SJ Wiback","year":"2004","journal-title":"Biotechnol Bioeng"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1103\/PhysRev.106.620","article-title":"Information Theory and Statistical Mechanics","volume":"106","author":"ET Jaynes","year":"1957","journal-title":"Phys Rev"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jtbi.2004.02.006","article-title":"Monte Carlo sampling can be used to determine the size and shape of the steady-state flux space","volume":"228","author":"SJ Wiback","year":"2004","journal-title":"J Theor Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1126\/science.277.5331.1453","article-title":"The Complete Genome Sequence of Escherichia coli K-12","volume":"277","author":"FR Blattner","year":"1997","journal-title":"Sci"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1074\/mcp.D500002-MCP200","article-title":"Comprehensive Analysis of a Multidimensional Liquid Chromatography Mass Spectrometry Dataset Acquired on a Quadrupole Selecting, Quadrupole Collision Cell, Time-of-flight Mass Spectrometer: II. New Developments in Protein Prospector Allow for Reliable and","volume":"4","author":"RJ Chalkley","year":"2005","journal-title":"Mol Cell Proteomics"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1021\/pr900863u","article-title":"Value of Using Multiple Proteases for Large-Scale Mass Spectrometry-Based Proteomics","volume":"9","author":"DL Swaney","year":"2010","journal-title":"J Proteome Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5327","DOI":"10.1128\/jb.169.11.5327-5329.1987","article-title":"Pathway of acetate assimilation in autotrophic and heterotrophic methanococci","volume":"169","author":"JS Shieh","year":"1987","journal-title":"J Bacteriol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1752-0509-6-9","article-title":"Predicting outcomes of steady-state 13C isotope tracing experiments using Monte Carlo sampling","volume":"6","author":"J Schellenberger","year":"2012","journal-title":"BMC Syst Biol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/mas.20071","article-title":"Advances in proteomics data analysis and display using an accurate mass and time tag approach","volume":"25","author":"JSD Zimmer","year":"2006","journal-title":"Mass Spectrom Rev"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T07:01:30Z","timestamp":1717311690000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003827"}},"subtitle":[],"editor":[{"given":"Christos A.","family":"Ouzounis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,9,4]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,9,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003827","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,4]]}}}