Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis

Mie Bech Lukassen, Wagma Saei, Teis Esben Sondergaard, Anu Tamminen, Abhishek Kumar, Frank Kempken, Marilyn G. Wiebe, Jens Laurids Sørensen

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17 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4331-4343
JournalMarine Drugs
Volume13
Issue number7
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Keywords

  • 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. (2015). Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis. Marine Drugs, 13(7), 4331-4343. https://doi.org/10.3390/md13074331