title: Motif-independent prediction of a secondary metabolism gene cluster using comparative genomics: application to sequenced genomes of Aspergillus and ten other filamentous fungal species.
abstract: Despite their biological importance, a significant number of genes for secondary metabolite biosynthesis (SMB) remain undetected due largely to the fact that they are highly diverse and are not expressed under a variety of cultivation conditions. Several software tools including SMURF and antiSMASH have been developed to predict fungal SMB gene clusters by finding core genes encoding polyketide synthase, nonribosomal peptide synthetase and dimethylallyltryptophan synthase as well as several others typically present in the cluster. In this work, we have devised a novel comparative genomics method to identify SMB gene clusters that is independent of motif information of the known SMB genes. The method detects SMB gene clusters by searching for a similar order of genes and their presence in nonsyntenic blocks. With this method, we were able to identify many known SMB gene clusters with the core genes in the genomic sequences of 10 filamentous fungi. Furthermore, we have also detected SMB gene clusters without core genes, including the kojic acid biosynthesis gene cluster of Aspergillus oryzae. By varying the detection parameters of the method, a significant difference in the sequence characteristics was detected between the genes residing inside the clusters and those outside the clusters.
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi 1-1-1, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Takeda
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi-Nijo 17-2-1, Tsukisamu, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Myco
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi 1-1-1, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi Chiba 277-8561, Japan Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo Waterfront Bio-IT Research Building, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asai
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi 1-1-1, Tsukuba, Ibaraki 305-8566, Japan Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi-Nijo 17-2-1, Tsukisamu, Sapporo, Hokkaido 062-8517, Japan m.machida@aist.go.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Machida
mesh_terms: D001230:Aspergillus / Q000235:genetics*; D016681:Genome, Fungal; D023281:Genomics; D005810:Multigene Family; D064210:Secondary Metabolism / Q000235:genetics*; D012984:Software
keywords: bioinformatics; filamentous fungi; secondary metabolism
references.citation: Fungal Genet Biol. 2010 Sep;47(9):736-41
references.pmid: 20554054
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W204-12
references.pmid: 23737449
references.citation: Nature. 2005 Dec 22;438(7071):1157-61
references.pmid: 16372010
references.citation: Genome Biol Evol. 2012;4(3):289-93
references.pmid: 22294497
references.citation: Curr Biol. 2011 Jan 25;21(2):134-9
references.pmid: 21194949
references.citation: Nat Biotechnol. 2007 Feb;25(2):221-31
references.pmid: 17259976
references.citation: DNA Res. 2008 Aug;15(4):173-83
references.pmid: 18820080
references.citation: PLoS One. 2012;7(7):e41903
references.pmid: 22860027
references.citation: DNA Res. 2012 Oct;19(5):375-82
references.pmid: 22912434
references.citation: J Mol Evol. 1981;18(1):38-46
references.pmid: 7334527
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Nat Rev Microbiol. 2005 Dec;3(12):937-47
references.pmid: 16322742
references.citation: Nucleic Acids Res. 2008 Dec;36(21):6882-92
references.pmid: 18978015
references.citation: PLoS Pathog. 2009 Jun;5(6):e1000486
references.pmid: 19557154
references.citation: FEBS J. 2011 Apr;278(7):1047-63
references.pmid: 21281447
references.citation: Nat Prod Rep. 2012 Mar;29(3):351-71
references.pmid: 22228366
references.citation: J Biotechnol. 2009 Mar 10;140(1-2):13-7
references.pmid: 19297688
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E99-107
references.pmid: 23248299
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W339-46
references.pmid: 21672958
references.citation: Trends Microbiol. 2013 Jan;21(1):14-22
references.pmid: 23084572
references.citation: Chembiochem. 2006 Jul;7(7):1062-9
references.pmid: 16755625
references.citation: Fungal Genet Biol. 2010 Dec;47(12):953-61
references.pmid: 20849972
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: J Mol Biol. 1981 Mar 25;147(1):195-7
references.pmid: 7265238
references.citation: Nat Chem Biol. 2007 Apr;3(4):213-7
references.pmid: 17369821
references.citation: PLoS One. 2013 May 07;8(5):e63673
references.pmid: 23667655