title: The RAVEN toolbox and its use for generating a genome-scale metabolic model for Penicillium chrysogenum.
abstract: We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Agren
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
authors.forename: Saeed
authors.initials: S
authors.lastname: Shoaie
authors.forename: Wanwipa
authors.initials: W
authors.lastname: Vongsangnak
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D057005:Bioengineering; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D010406:Penicillins / Q000378:metabolism; D010408:Penicillium chrysogenum / Q000235:genetics* / Q000378:metabolism*; D012984:Software
chemical_list: D010406:Penicillins; D009249:NADP; D000255:Adenosine Triphosphate
references.citation: Proteins. 2006 Aug 15;64(3):643-51
references.pmid: 16752418
references.citation: Biotechnol Bioeng. 1995 Apr 20;46(2):117-31
references.pmid: 18623271
references.citation: Nat Protoc. 2007;2(3):727-38
references.pmid: 17406635
references.citation: Biotechnol Prog. 1995 May-Jun;11(3):299-305
references.pmid: 7619400
references.citation: Genome Res. 2003 Feb;13(2):244-53
references.pmid: 12566402
references.citation: Genome Biol. 2003;4(9):R54
references.pmid: 12952533
references.citation: Mol Syst Biol. 2008;4:178
references.pmid: 18364712
references.citation: Nucleic Acids Res. 2005 Mar 03;33(4):1399-409
references.pmid: 15745999
references.citation: Metab Eng. 2006 Mar;8(2):91-101
references.pmid: 16253533
references.citation: Nat Rev Microbiol. 2009 Feb;7(2):129-43
references.pmid: 19116616
references.citation: Methods Mol Biol. 2001;177:v-viii
references.pmid: 11530620
references.citation: FEBS Lett. 2010 Jun 18;584(12):2556-64
references.pmid: 20420838
references.citation: Nat Biotechnol. 2008 Oct;26(10):1161-8
references.pmid: 18820685
references.citation: Nat Protoc. 2010 Jan;5(1):93-121
references.pmid: 20057383
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):47-9
references.pmid: 11752250
references.citation: BMC Bioinformatics. 2003 Sep 11;4:41
references.pmid: 12969510
references.citation: Metab Eng. 2003 Jan;5(1):56-69
references.pmid: 12749845
references.citation: PLoS Comput Biol. 2012;8(5):e1002518
references.pmid: 22615553
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2685-9
references.pmid: 15710883
references.citation: Metab Eng. 2005 May;7(3):155-64
references.pmid: 15885614
references.citation: Appl Microbiol Biotechnol. 2003 Jun;61(5-6):385-92
references.pmid: 12679848
references.citation: Nat Biotechnol. 2008 Oct;26(10):1155-60
references.pmid: 18846089
references.citation: Biotechnol Bioeng. 1998 Dec 20;60(6):761-7
references.pmid: 10099485
references.citation: Bioinformatics. 2000 Dec;16(12):1145-50
references.pmid: 11159333
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33
references.pmid: 10805808
references.citation: Proteins. 1997 Jul;28(3):405-20
references.pmid: 9223186
references.citation: PLoS Comput Biol. 2010 Jul 15;6(7):e1000859
references.pmid: 20657658
references.citation: Trends Biotechnol. 2003 Apr;21(4):162-9
references.pmid: 12679064
references.citation: BMC Syst Biol. 2008 Aug 07;2:71
references.pmid: 18687109
references.citation: BMC Genomics. 2008 May 23;9:245
references.pmid: 18500999
references.citation: Biotechnol Bioeng. 2010 Feb 15;105(3):439-60
references.pmid: 19891008
references.citation: Genome Biol. 2006;7(11):R108
references.pmid: 17107606
references.citation: BMC Bioinformatics. 2004 Aug 16;5:112
references.pmid: 15312235
references.citation: Biophys J. 2004 Oct;87(4):2172-86
references.pmid: 15454420
references.citation: Behav Brain Res. 2001 Nov 1;125(1-2):279-84
references.pmid: 11682119
references.citation: Biotechnol Bioeng. 2005 Sep 5;91(5):643-8
references.pmid: 15962337
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Nat Biotechnol. 2005 Dec;23(12):1509-15
references.pmid: 16333295
references.citation: BMC Bioinformatics. 2006 Jun 13;7:296
references.pmid: 16772023
references.citation: Nucleic Acids Res. 1999 Jan 1;27(1):29-34
references.pmid: 9847135
references.citation: Bioinformatics. 1998;14(9):755-63
references.pmid: 9918945
references.citation: Bioinformatics. 2005 Nov 1;21(21):3963-9
references.pmid: 16144808
references.citation: Mol Syst Biol. 2006;2:50
references.pmid: 17016516
references.citation: Nat Biotechnol. 2010 Sep;28(9):977-82
references.pmid: 20802497
references.citation: Appl Microbiol Biotechnol. 1995 Apr;43(1):123-30
references.pmid: 7766125
references.citation: Bioinformatics. 2011 Jan 1;27(1):142-3
references.pmid: 21115436
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W585-7
references.pmid: 17517783
references.citation: Bioinformatics. 2003 Mar 1;19(4):524-31
references.pmid: 12611808
references.citation: BMC Bioinformatics. 2006 Mar 23;7:168
references.pmid: 16553966
references.citation: Arch Microbiol. 1980 Dec;128(2):253-5
references.pmid: 6782999
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references.pmid: 15034147
references.citation: Biotechnol Bioeng. 2001 Feb 20;72(4):379-88
references.pmid: 11180058
references.citation: Trends Biotechnol. 1999 Feb;17(2):53-60
references.pmid: 10087604
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W144-9
references.pmid: 20483918