Identification of the Scopularide Biosynthetic Gene Cluster in Scopulariopsis brevicaulis

Marine Drugs

Mie Bech Lukassen¹  Wagma Saei¹  Teis Esben Sondergaard¹  Anu Tamminen²  Abhishek Kumar³  Frank Kempken³  Marilyn G. Wiebe²  Jens Laurids Sørensen¹ 

[1] Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, DK-9220 Aalborg Ø, Denmark; E-Mails:;VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT, Finland; E-Mails:;Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany; E-Mails:

关键词: non-ribosomal peptide synthetases;    polyketide synthases;    secondary metabolites;    transcription factor;    Fusarium;    regulation;    marine fungi;   

DOI  :  10.3390/md13074331

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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