{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:52:00Z","timestamp":1773078720215,"version":"3.50.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2013,3,21]],"date-time":"2013-03-21T00:00:00Z","timestamp":1363824000000},"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.1002980","type":"journal-article","created":{"date-parts":[[2013,3,21]],"date-time":"2013-03-21T16:49:33Z","timestamp":1363884573000},"page":"e1002980","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":355,"title":["The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum"],"prefix":"10.1371","volume":"9","author":[{"given":"Rasmus","family":"Agren","sequence":"first","affiliation":[]},{"given":"Liming","family":"Liu","sequence":"additional","affiliation":[]},{"given":"Saeed","family":"Shoaie","sequence":"additional","affiliation":[]},{"given":"Wanwipa","family":"Vongsangnak","sequence":"additional","affiliation":[]},{"given":"Intawat","family":"Nookaew","sequence":"additional","affiliation":[]},{"given":"Jens","family":"Nielsen","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,3,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1016\/j.febslet.2010.04.052","article-title":"Use of genome-scale metabolic models for understanding microbial physiology","volume":"584","author":"L Liu","year":"2010","journal-title":"FEBS Lett"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S0167-7799(03)00030-1","article-title":"Genome-scale microbial in silico models: the constraints-based approach","volume":"21","author":"ND Price","year":"2003","journal-title":"Trends Biotechnol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1529\/biophysj.104.043000","article-title":"Uniform sampling of steady-state flux spaces: means to design experiments and to interpret enzymopathies","volume":"87","author":"ND Price","year":"2004","journal-title":"Biophys J"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e1000859","DOI":"10.1371\/journal.pcbi.1000859","article-title":"Sampling the solution space in genome-scale metabolic networks reveals transcriptional regulation in key enzymes","volume":"6","author":"S Bordel","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0167-7799(98)01290-6","article-title":"Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering","volume":"17","author":"S Schuster","year":"1999","journal-title":"Trends Biotechnol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/bit.20542","article-title":"In silico design and adaptive evolution of Escherichia coli for production of lactic acid","volume":"91","author":"SS Fong","year":"2005","journal-title":"Biotechnol Bioeng"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ymben.2004.12.003","article-title":"Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli","volume":"7","author":"H Alper","year":"2005","journal-title":"Metab Eng"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/msb4100085","article-title":"Integration of metabolome data with metabolic networks reveals reporter reactions","volume":"2","author":"T Cakir","year":"2006","journal-title":"Mol Syst Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nrmicro1949","article-title":"Reconstruction of biochemical networks in microorganisms","volume":"7","author":"AM Feist","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1101\/gr.234503","article-title":"Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network","volume":"13","author":"J Forster","year":"2003","journal-title":"Genome Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1073\/pnas.97.10.5528","article-title":"The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities","volume":"97","author":"JS Edwards","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/bit.22592","article-title":"Industrial Systems Biology","volume":"105","author":"JM Otero","year":"2009","journal-title":"Biotechnology and Bioengineering"},{"key":"ref13","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":"R Apweiler","year":"2000","journal-title":"Bioinformatics"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/(SICI)1097-0134(199707)28:3<405::AID-PROT10>3.0.CO;2-L","article-title":"Pfam: a comprehensive database of protein domain families based on seed alignments","volume":"28","author":"EL Sonnhammer","year":"1997","journal-title":"Proteins"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nprot.2009.203","article-title":"A protocol for generating a high-quality genome-scale metabolic reconstruction","volume":"5","author":"I Thiele","year":"2010","journal-title":"Nature Protocols"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"27","author":"H Ogata","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/1471-2105-7-168","article-title":"GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes","volume":"7","author":"K Arakawa","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/1471-2105-7-296","article-title":"Accelerating the reconstruction of genome-scale metabolic networks","volume":"7","author":"RA Notebaart","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/nar\/gki285","article-title":"metaSHARK: software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella","volume":"33","author":"JW Pinney","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/nbt.1672","article-title":"High-throughput generation, optimization and analysis of genome-scale metabolic models","volume":"28","author":"CS Henry","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nprot.2007.99","article-title":"Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox","volume":"2","author":"SA Becker","year":"2007","journal-title":"Nature Protocols"},{"key":"ref22","unstructured":"Pitt JI (1979) The genus Penicillium and its teleomorphic states Eupenicillium and Talaromyces. New York: Academic Press. 634 p."},{"key":"ref23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00253-003-1274-y","article-title":"Industrial production of beta-lactam antibiotics","volume":"61","author":"RP Elander","year":"2003","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1096-7176(03)00003-X","article-title":"Metabolic engineering of beta-lactam production","volume":"5","author":"J Thykaer","year":"2003","journal-title":"Metab Eng"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/bioinformatics\/btg015","article-title":"The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models","volume":"19","author":"M Hucka","year":"2003","journal-title":"Bioinformatics"},{"key":"ref26","first-page":"131","article-title":"An open standard for chemical structure representation: The IUPAC Chemical Identifier","author":"SE Stein","year":"2003","journal-title":"Proceedings of the 2003 International Chemical Information Conference"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nbt1492","article-title":"A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology","volume":"26","author":"MJ Herrgard","year":"2008","journal-title":"Nat Biotechnol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"W144","DOI":"10.1093\/nar\/gkq404","article-title":"BioMet Toolbox: genome-wide analysis of metabolism","volume":"38","author":"M Cvijovic","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/nar\/30.1.47","article-title":"BRENDA, enzyme data and metabolic information","volume":"30","author":"I Schomburg","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/bioinformatics\/btq607","article-title":"von Bertalanffy 1.0: a COBRA toolbox extension to thermodynamically constrain metabolic models","volume":"27","author":"RM Fleming","year":"2011","journal-title":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"RC Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"SR Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1145\/356044.356048","article-title":"Space-Efficient Implementations of Graph Search Methods","volume":"9","author":"RE Tarjan","year":"1983","journal-title":"Acm Transactions on Mathematical Software"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"W585","DOI":"10.1093\/nar\/gkm259","article-title":"WoLF PSORT: protein localization predictor","volume":"35","author":"P Horton","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/prot.21018","article-title":"Prediction of protein subcellular localization","volume":"64","author":"CS Yu","year":"2006","journal-title":"Proteins"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1752-0509-2-71","article-title":"The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism","volume":"2","author":"I Nookaew","year":"2008","journal-title":"BMC Syst Biol"},{"key":"ref38","first-page":"v","article-title":"Two-hybrid systems. Methods and protocols. Introduction","volume":"177","author":"PN McDonald","year":"2001","journal-title":"Methods Mol Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1109\/JPROC.2008.925458","article-title":"CellDesigner 3.5: A versatile modeling tool for biochemical networks","volume":"96","author":"A Funahashi","year":"2008","journal-title":"Proceedings of the Ieee"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1038\/nbt1156","article-title":"Minimum information requested in the annotation of biochemical models (MIRIAM)","volume":"23","author":"N Le Novere","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"R54","DOI":"10.1186\/gb-2003-4-9-r54","article-title":"An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM\/GPR)","volume":"4","author":"JL Reed","year":"2003","journal-title":"Genome Biol"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Nielsen J (1997) Physiological engineering aspects of Penicillium chrysogenum. Singapore: World Scientific. 269 p.","DOI":"10.1142\/3195"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/(SICI)1097-0290(19981220)60:6<761::AID-BIT12>3.0.CO;2-N","article-title":"Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane potential of Penicillium chrysogenum","volume":"60","author":"CM Henriksen","year":"1998","journal-title":"Biotechnol Bioeng"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/bit.260460205","article-title":"Metabolic flux distributions in Penicillium chrysogenum during fed-batch cultivations","volume":"46","author":"H Jorgensen","year":"1995","journal-title":"Biotechnol Bioeng"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ymben.2005.09.004","article-title":"Enzymic analysis of NADPH metabolism in beta-lactam-producing Penicillium chrysogenum: presence of a mitochondrial NADPH dehydrogenase","volume":"8","author":"DM Harris","year":"2006","journal-title":"Metab Eng"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1073\/pnas.0406811102","article-title":"Uncovering transcriptional regulation of metabolism by using metabolic network topology","volume":"102","author":"KR Patil","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/1097-0290(20000220)72:4<379::AID-BIT1000>3.0.CO;2-5","article-title":"Quantitative analysis of Penicillium chrysogenum Wis54-1255 transformants overexpressing the penicillin biosynthetic genes","volume":"72","author":"H Theilgaard","year":"2001","journal-title":"Biotechnol Bioeng"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00170633","article-title":"Analysis of penicillin V biosynthesis during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum","volume":"43","author":"H Jorgensen","year":"1995","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1021\/bp00033a010","article-title":"Metabolic control analysis of the penicillin biosynthetic pathway in a high-yielding strain of Penicillium chrysogenum","volume":"11","author":"J Nielsen","year":"1995","journal-title":"Biotechnol Prog"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s002530051348","article-title":"Identification and purification of O-acetyl-L-serine sulphhydrylase in Penicillium chrysogenum","volume":"50","author":"S Ostergaard","year":"1998","journal-title":"Applied Microbiology and Biotechnology"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"R108","DOI":"10.1186\/gb-2006-7-11-r108","article-title":"Metabolic network driven analysis of genome-wide transcription data from Aspergillus nidulans","volume":"7","author":"H David","year":"2006","journal-title":"Genome Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/msb.2008.12","article-title":"Metabolic model integration of the bibliome, genome, metabolome and reactome of Aspergillus niger","volume":"4","author":"MR Andersen","year":"2008","journal-title":"Mol Syst Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/1471-2164-9-245","article-title":"Improved annotation through genome-scale metabolic modeling of Aspergillus oryzae","volume":"9","author":"W Vongsangnak","year":"2008","journal-title":"BMC Genomics"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1093\/bioinformatics\/bti650","article-title":"pTARGET [corrected] a new method for predicting protein subcellular localization in eukaryotes","volume":"21","author":"C Guda","year":"2005","journal-title":"Bioinformatics"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF00406168","article-title":"The Distribution of the Nadph-Regenerating Mannitol Cycle among Fungal Species","volume":"128","author":"K Hult","year":"1980","journal-title":"Archives of Microbiology"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/nbt.1498","article-title":"Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum","volume":"26","author":"MA van den Berg","year":"2008","journal-title":"Nat Biotechnol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","article-title":"Controlling the false discovery rate in behavior genetics research","volume":"125","author":"Y Benjamini","year":"2001","journal-title":"Behav Brain Res"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e1002518","DOI":"10.1371\/journal.pcbi.1002518","article-title":"Reconstruction of genome-scale active metabolic networks for 69 human cell types and 16 cancer types using INIT","volume":"8","author":"R Agren","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1471-2105-5-112","article-title":"IdentiCS\u2013identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence","volume":"5","author":"J Sun","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1471-2105-4-41","article-title":"The COG database: an updated version includes eukaryotes","volume":"4","author":"RL Tatusov","year":"2003","journal-title":"BMC Bioinformatics"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002980","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T12:19:30Z","timestamp":1540297170000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002980"}},"subtitle":[],"editor":[{"given":"Costas D.","family":"Maranas","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,3,21]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,3,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002980","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,21]]}}}