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

16 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

Fingerprint

Scopulariopsis
Multigene Family
Transcription Factors
Peptide Synthases
Polyketide Synthases
Lipopeptides
Acyltransferases
Aspergillus nidulans
Homologous Recombination
Fusarium
Valine
Coenzyme A
Ligases
Phenylalanine
Leucine
Alanine
Glycine
Carbon
Genome
Amino Acids

Keywords

  • non-ribosomal peptide synthetases
  • polyketide synthases
  • secondary metabolites
  • transcription factor
  • Fusarium
  • regulation
  • marine fungi

Cite this

Lukassen, M. B., Saei, W., Sondergaard, T. E., Tamminen, A., Kumar, A., Kempken, F., ... 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
Lukassen, Mie Bech ; Saei, Wagma ; Sondergaard, Teis Esben ; Tamminen, Anu ; Kumar, Abhishek ; Kempken, Frank ; Wiebe, Marilyn G. ; Sørensen, Jens Laurids. / Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis. In: Marine Drugs. 2015 ; Vol. 13, No. 7. pp. 4331-4343.
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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.",
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Lukassen, MB, Saei, W, Sondergaard, TE, Tamminen, A, Kumar, A, Kempken, F, Wiebe, MG & Sørensen, JL 2015, 'Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis', Marine Drugs, vol. 13, no. 7, pp. 4331-4343. https://doi.org/10.3390/md13074331

Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis. / Lukassen, Mie Bech; Saei, Wagma; Sondergaard, Teis Esben; Tamminen, Anu; Kumar, Abhishek; Kempken, Frank; Wiebe, Marilyn G.; Sørensen, Jens Laurids.

In: Marine Drugs, Vol. 13, No. 7, 2015, p. 4331-4343.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis

AU - Lukassen, Mie Bech

AU - Saei, Wagma

AU - Sondergaard, Teis Esben

AU - Tamminen, Anu

AU - Kumar, Abhishek

AU - Kempken, Frank

AU - Wiebe, Marilyn G.

AU - Sørensen, Jens Laurids

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - non-ribosomal peptide synthetases

KW - polyketide synthases

KW - secondary metabolites

KW - transcription factor

KW - Fusarium

KW - regulation

KW - marine fungi

U2 - 10.3390/md13074331

DO - 10.3390/md13074331

M3 - Article

VL - 13

SP - 4331

EP - 4343

JO - Marine Drugs

JF - Marine Drugs

SN - 1660-3397

IS - 7

ER -