{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:45:28Z","timestamp":1791193528886,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T00:00:00Z","timestamp":1338422400000},"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.1002540","type":"journal-article","created":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T21:04:15Z","timestamp":1338498255000},"page":"e1002540","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["The CanOE Strategy: Integrating Genomic and Metabolic Contexts across Multiple Prokaryote Genomes to Find Candidate Genes for Orphan Enzymes"],"prefix":"10.1371","volume":"8","author":[{"given":"Adam Alexander Thil","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugeni","family":"Belda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Viari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Medigue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vallenet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,5,31]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"bar009","DOI":"10.1093\/database\/bar009","article-title":"UniProt Knowledgebase: a hub of integrated protein data.","volume":"2011","author":"M Magrane","year":"2011","journal-title":"Database"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00018-005-5520-6","article-title":"Puzzling over orphan enzymes.","volume":"63","author":"O Lespinet","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/1471-2105-8-244","article-title":"A survey of orphan enzyme activities.","volume":"8","author":"Y Pouliot","year":"2007","journal-title":"BMC Bioinf"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.tibtech.2007.06.001","article-title":"Distribution of orphan metabolic activities.","volume":"25","author":"L Chen","year":"2007","journal-title":"Trends Biotechnol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1073\/pnas.96.6.2896","article-title":"The use of gene clusters to infer functional coupling.","volume":"96","author":"R Overbeek","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1073\/pnas.96.8.4285","article-title":"Assigning protein functions by comparative genome analysis: Protein phylogenetic profiles.","volume":"96","author":"M Pellegrini","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.285.5428.751","article-title":"Detecting protein function and protein-protein interactions from genome sequences.","volume":"285","author":"EM Marcotte","year":"1999","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/47048","article-title":"A combined algorithm for genome-wide prediction of protein function.","volume":"402","author":"EM Marcotte","year":"1999","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S1367-5931(03)00027-9","article-title":"Missing genes in metabolic pathways: a comparative genomics approach.","volume":"7","author":"A Osterman","year":"2003","journal-title":"Curr Opin Chem Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"D382","DOI":"10.1093\/nar\/gkp887","article-title":"The integrated microbial genomes system: an expanding comparative analysis resource.","volume":"38","author":"VM Markowitz","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/nar\/gkj406","article-title":"MaGe: a microbial genome annotation system supported by synteny results.","volume":"34","author":"D Vallenet","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref12","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bap021","article-title":"MicroScope: a platform for microbial genome annotation and comparative genomics.","author":"D Vallenet","year":"2009"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1093\/nar\/gki866","article-title":"The SEED : The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes.","volume":"33","author":"R Overbeek","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/nar\/gkg148","article-title":"The ERGO genome analysis and discovery system.","volume":"31","author":"R Overbeek","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"i205","DOI":"10.1093\/bioinformatics\/btm213","article-title":"Using genome-context data to identify specific types of functional associations in pathway\/genome databases.","volume":"23","author":"ML Green","year":"2007","journal-title":"Bioinformatics (Oxford)"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2105-5-76","article-title":"A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases.","volume":"5","author":"M Green","year":"2004","journal-title":"BMC Bioinf"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1093\/nar\/gkl438","article-title":"The outcomes of pathway database computations depend on pathway ontology.","volume":"34","author":"ML Green","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1471-2105-7-177","article-title":"Identifying metabolic enzymes with multiple types of association evidence.","volume":"7","author":"P Kharchenko","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1111\/j.1742-4658.2007.05763.x","article-title":"Prediction of missing enzyme genes in a bacterial metabolic network.","volume":"274","author":"Y Yamanishi","year":"2007","journal-title":"FEBS J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1471-2105-12-S1-S1","article-title":"Genome-wide discovery of missing genes in biological pathways of prokaryotes.","volume":"12","author":"Y Chen","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"D561","DOI":"10.1093\/nar\/gkq973","article-title":"The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored.","volume":"39","author":"D Szklarczyk","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"15638","DOI":"10.1074\/jbc.M800487200","article-title":"New insights into the alternative D-glucarate degradation pathway.","volume":"283","author":"A Aghaie","year":"2008","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1128\/JB.01777-08","article-title":"A conserved gene cluster rules anaerobic oxidative degradation of L-ornithine.","volume":"191","author":"N Fonknechten","year":"2009","journal-title":"J Bacteriol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"7191","DOI":"10.1074\/jbc.M609829200","article-title":"Identification of the Last Unknown Genes in the Fermentation Pathway of Lysine.","volume":"282","author":"A Kreimeyer","year":"2007","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1093\/nar\/28.20.4021","article-title":"A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters.","volume":"28","author":"H Ogata","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1093\/bioinformatics\/bti711","article-title":"Syntons, metabolons and interactons: an exact graph-theoretical approach for exploring neighbourhood between genomic and functional data.","volume":"21","author":"F Boyer","year":"2005","journal-title":"Bioinformatics"},{"key":"ref27","article-title":"Recovering isofunctional genes: a multiple genomes synteny-based approach in JOBIM 2008 (Lille).","author":"Y-P Denielou","year":"2008"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.bi.56.070187.000513","article-title":"Complexes of Sequential Metabolic Enzymes.","volume":"56","author":"PA Srere","year":"1987","journal-title":"Annu Rev Biochem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(85)80030-1","article-title":"A bidirectional rho-independent transcription terminator between the <italic>E. coli<\/italic> tonB gene and an opposing gene.","volume":"41","author":"K Postle","year":"1985","journal-title":"Cell"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/S0968-0004(00)01663-7","article-title":"Gene context conservation of a higher order than operons.","volume":"25","author":"WC Lathe 3rd","year":"2000","journal-title":"Trends Biochem Sci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1093\/nar\/gkl294","article-title":"Detecting uber-operons in prokaryotic genomes.","volume":"34","author":"D Che","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"D623","DOI":"10.1093\/nar\/gkm900","article-title":"The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway\/Genome Databases.","volume":"36","author":"R Caspi","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"D754","DOI":"10.1093\/nar\/gkr1126","article-title":"Rhea\u2013a manually curated resource of biochemical reactions.","volume":"40","author":"R Alc\u00e1ntara","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"D355","DOI":"10.1093\/nar\/gkp896","article-title":"KEGG for representation and analysis of molecular networks involving diseases and drugs.","volume":"38","author":"M Kanehisa","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"D583","DOI":"10.1093\/nar\/gkq1143","article-title":"EcoCyc: a comprehensive database of <italic>Escherichia coli<\/italic> biology.","volume":"39","author":"IM Keseler","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/bib\/bbp043","article-title":"Pathway Tools version 13.0: integrated software for pathway\/genome informatics and systems biology.","volume":"11","author":"PD Karp","year":"2010","journal-title":"Briefings Bioinf"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/bit.22844","article-title":"Systematizing the generation of missing metabolic knowledge.","volume":"107","author":"JD Orth","year":"2010","journal-title":"Biotechnol Bioeng"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"D98","DOI":"10.1093\/nar\/gkq1110","article-title":"RegulonDB version 7.0: transcriptional regulation of <italic>Escherichia coli<\/italic> K-12 integrated within genetic sensory response units (Gensor Units).","volume":"39","author":"S Gama-Castro","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1101\/gr.1224503","article-title":"OrthoMCL: Identification of Ortholog Groups for Eukaryotic Genomes.","volume":"13","author":"L Li","year":"2003","journal-title":"Genome Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology.","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/bioinformatics\/16.12.1145","article-title":"InterPro\u2013an integrated documentation resource for protein families, domains and functional sites.","volume":"16","author":"NJ Mulder","year":"2000","journal-title":"Bioinformatics (Oxford)"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"i178","DOI":"10.1093\/bioinformatics\/bth930","article-title":"Filling gaps in a metabolic network using expression information.","volume":"20","author":"P Kharchenko","year":"2004","journal-title":"Bioinformatics (Oxford)"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1128\/JB.87.1.75-80.1964","article-title":"Oxamic Transbarbamylase of <italic>Streptococcus allantoicus<\/italic>.","volume":"87","author":"R Bojanowski","year":"1964","journal-title":"J Bacteriol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0006-291X(65)90506-1","article-title":"Induction of Carbamyl-P specific Oxamate Transcarbamylase by Parabanic acid in a <italic>Streptococcus<\/italic>.","volume":"19","author":"H Tigier","year":"1965","journal-title":"Biochem Biophys Res Commun"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"7479","DOI":"10.1128\/JB.181.24.7479-7484.1999","article-title":"Genetic Analysis of a Chromosomal Region Containing Genes Required for Assimilation of Allantoin Nitrogen and Linked Glyoxylate Metabolism in <italic>Escherichia coli<\/italic>.","volume":"181","author":"E Cusa","year":"1999","journal-title":"J Bacteriol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/prot.23043","article-title":"The ygeW encoded protein from <italic>Escherichia coli<\/italic> is a knotted ancestral catabolic transcarbamylase.","volume":"79","author":"Y Li","year":"2011","journal-title":"Proteins: Struct, Funct, Bioinf"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1186\/1471-2105-11-493","article-title":"A systematic study of genome context methods: calibration, normalization and combination.","volume":"11","author":"L Ferrer","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.sbi.2009.02.001","article-title":"Is protein classification necessary? Towards alternative approaches to function annotation.","volume":"19","author":"D Petrey","year":"2009","journal-title":"Curr Opin Struct Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"D11","DOI":"10.1093\/nar\/gkq1168","article-title":"COMBREX: a project to accelerate the functional annotation of prokaryotic genomes.","volume":"39","author":"RJ Roberts","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"9950","DOI":"10.1021\/bi201312u","article-title":"The Enzyme Function Initiative.","volume":"50","author":"JA Gerlt","year":"2011","journal-title":"Biochemistry"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002540","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T08:14:19Z","timestamp":1594196059000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002540"}},"subtitle":[],"editor":[{"given":"Christos A.","family":"Ouzounis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,5,31]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2012,5,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002540","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,31]]}}}