Mar. Drugs 2015, 13(7), 4331-4343; https://doi.org/10.3390/md13074331
Identification of the Scopularide Biosynthetic Gene Cluster in Scopulariopsis brevicaulis
Mie Bech Lukassen 1, Wagma Saei 1, Teis Esben Sondergaard 1, Anu Tamminen 2, Abhishek Kumar 3, Frank Kempken 3, Marilyn G. Wiebe 2 and Jens Laurids Sørensen 1,4,*
1
Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark
2
VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT, Finland
3
Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany
4
Department of Chemistry and Bioscience, Aalborg University, Niels Bohrs Vej 8, DK-6700 Esbjerg, Denmark
*
Author to whom correspondence should be addressed.
Academic Editor: Johannes F. Imhoff
Received: 20 March 2015 / Revised: 2 July 2015 / Accepted: 3 July 2015 / Published: 14 July 2015
(This article belongs to the Special Issue Bioactive Compounds from Marine Fungi)
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. View Full-TextKeywords:
non-ribosomal peptide synthetases; polyketide synthases; secondary metabolites; transcription factor; Fusarium; regulation; marine fungi
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Lukassen, M.B.; Saei, W.; Sondergaard, T.E.; Tamminen, A.; Kumar, A.; Kempken, F.; Wiebe, M.G.; Sørensen, J.L. Identification of the Scopularide Biosynthetic Gene Cluster in Scopulariopsis brevicaulis. Mar. Drugs 2015, 13, 4331-4343.
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