title: Identification of the Scopularide Biosynthetic Gene Cluster in Scopulariopsis brevicaulis.
abstract: Scopularide A is a promising potent anticancer lipopeptide isolated from a marine derived Scopulariopsis brevicaulis strain. The compound consists of a reduced carbon chain (3-hydroxy-methyldecanoyl) attached to five amino acids (glycine, l-valine, d-leucine, l-alanine, and l-phenylalanine). Using the newly sequenced S. brevicaulis genome we were able to identify the putative biosynthetic gene cluster using genetic information from the structurally related emericellamide A from Aspergillus nidulans and W493-B from Fusarium pseudograminearum. The scopularide A gene cluster includes a nonribosomal peptide synthetase (NRPS1), a polyketide synthase (PKS2), a CoA ligase, an acyltransferase, and a transcription factor. Homologous recombination was low in S. brevicaulis so the local transcription factor was integrated randomly under a constitutive promoter, which led to a three to four-fold increase in scopularide A production. This indirectly verifies the identity of the proposed biosynthetic gene cluster.
authors.affiliation: Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark. mbl@bio.aau.dk.
authors.forename: Mie Bech
authors.initials: MB
authors.lastname: Lukassen
authors.affiliation: Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark. wagmasaei@gmail.com.
authors.forename: Wagma
authors.initials: W
authors.lastname: Saei
authors.affiliation: Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark. tes@bio.aau.dk.
authors.forename: Teis Esben
authors.initials: TE
authors.lastname: Sondergaard
authors.affiliation: VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT, Finland. Anu.Tamminen@vtt.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Tamminen
authors.affiliation: Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany. abhishek.abhishekkumar@gmail.com.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany. fkempken@bot.uni-kiel.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Kempken
authors.affiliation: VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT, Finland. marilyn.wiebe@vtt.fi.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Wiebe
authors.affiliation: Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark. jls@bio.aau.dk.|Department of Chemistry and Bioscience, Aalborg University, Niels Bohrs Vej 8, DK-6700 Esbjerg, Denmark. jls@bio.aau.dk.
authors.forename: Jens Laurids
authors.initials: JL
authors.lastname: Sørensen
mesh_terms: D002853:Chromatography, Liquid; D047630:Depsipeptides / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D013058:Mass Spectrometry; D005810:Multigene Family / Q000235:genetics; D060645:Scopulariopsis / Q000235:genetics* / Q000378:metabolism
chemical_list: D047630:Depsipeptides; C519738:emericellamide A; C531265:scopularide A
keywords: Fusarium; marine fungi; non-ribosomal peptide synthetases; polyketide synthases; regulation; secondary metabolites; transcription factor