title: Elucidation of primary metabolic pathways in Aspergillus species: orphaned research in characterizing orphan genes.
abstract: Primary metabolism affects all phenotypical traits of filamentous fungi. Particular examples include reacting to extracellular stimuli, producing precursor molecules required for cell division and morphological changes as well as providing monomer building blocks for production of secondary metabolites and extracellular enzymes. In this review, all annotated genes from four Aspergillus species have been examined. In this process, it becomes evident that 80-96% of the genes (depending on the species) are still without verified function. A significant proportion of the genes with verified metabolic functions are assigned to secondary or extracellular metabolism, leaving only 2-4% of the annotated genes within primary metabolism. It is clear that primary metabolism has not received the same attention in the post-genomic area as many other research areas--despite its role at the very centre of cellular function. However, several methods can be employed to use the metabolic networks in tandem with comparative genomics to accelerate functional assignment of genes in primary metabolism. In particular, gaps in metabolic pathways can be used to assign functions to orphan genes. In this review, applications of this from the Aspergillus genes will be examined, and it is proposed that, where feasible, this should be a standard part of functional annotation of fungal genomes.
authors.forename: Mikael Rørdam
authors.initials: MR
authors.lastname: Andersen
mesh_terms: D001230:Aspergillus / Q000145:classification / Q000235:genetics*; D035843:Biomedical Research; D019295:Computational Biology; D005800:Genes, Fungal; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D053858:Metabolic Networks and Pathways; D008954:Models, Biological
keywords: Aspergillus; functional genomics; metabolic networks; primary metabolism
references.citation: BMC Genomics. 2012 Jul 16;13:313
references.pmid: 22799883
references.citation: PLoS Comput Biol. 2014 Feb 06;10(2):e1003465
references.pmid: 24516375
references.citation: BMC Genomics. 2008 May 23;9:245
references.pmid: 18500999
references.citation: FEBS Lett. 2010 Aug 20;584(16):3540-4
references.pmid: 20654618
references.citation: Genome Biol. 2007;8(9):R182
references.pmid: 17784953
references.citation: Integr Biol (Camb). 2011 Nov;3(11):1071-86
references.pmid: 21952610
references.citation: Eukaryot Cell. 2012 Jan;11(1):68-78
references.pmid: 21724936
references.citation: PLoS Comput Biol. 2013;9(7):e1003126
references.pmid: 23935467
references.citation: BMC Genomics. 2008 Apr 11;9:163
references.pmid: 18405346
references.citation: Nat Protoc. 2010 Jan;5(1):93-121
references.pmid: 20057383
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D459-71
references.pmid: 24225315
references.citation: Appl Microbiol Biotechnol. 2003 May;61(3):189-96
references.pmid: 12698275
references.citation: Proc Natl Acad Sci U S A. 1941 Nov 15;27(11):499-506
references.pmid: 16588492
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W204-12
references.pmid: 23737449
references.citation: Nucleic Acids Res. 2007;35(22):7577-90
references.pmid: 17940092
references.citation: Nature. 2005 Dec 22;438(7071):1105-15
references.pmid: 16372000
references.citation: Nature. 2005 Dec 22;438(7071):1157-61
references.pmid: 16372010
references.citation: Biotechnol Biofuels. 2011 Oct 18;4:40
references.pmid: 22008461
references.citation: Fungal Genet Biol. 2009 Mar;46 Suppl 1:S161-S169
references.pmid: 19618505
references.citation: Nat Prod Rep. 2012 Mar;29(3):351-71
references.pmid: 22228366
references.citation: Fungal Genet Biol. 2009 Mar;46 Suppl 1:S19-S44
references.pmid: 19610199
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D653-9
references.pmid: 22080559
references.citation: Nat Biotechnol. 2007 Feb;25(2):221-31
references.pmid: 17259976
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D233-8
references.pmid: 18838391
references.citation: Proc Natl Acad Sci U S A. 1942 Jun;28(6):234-43
references.pmid: 16578042
references.citation: Genome Res. 2011 Jun;21(6):885-97
references.pmid: 21543515
references.citation: Biotechnol Adv. 2007 May-Jun;25(3):244-63
references.pmid: 17337335
references.citation: Nature. 2005 Dec 22;438(7071):1151-6
references.pmid: 16372009
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E99-107
references.pmid: 23248299
references.citation: Adv Genet. 1953;5:141-238
references.pmid: 13040135
references.citation: Biotechnol Biofuels. 2014 Apr 01;7(1):46
references.pmid: 24690493
references.citation: Mol Syst Biol. 2008;4:178
references.pmid: 18364712
references.citation: J Biol Chem. 2012 Jul 27;287(31):26010-8
references.pmid: 22654107