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

    Research output: Contribution to journalArticleScientificpeer-review

    19 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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