Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum

Jens Laurids Sørensen; Frederik Teilfeldt Hansen; Teis Esben Søndergaard; Dan Stærk; T. Verne Lee; Reinhard Wimmer; Louise Graabæk Klitgaard; Stig Purup; Henriette Giese; Rasmus John Normand Frandsen

doi:10.1111/j.1462-2920.2011.02696.x

Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum

Jens Laurids Sørensen, Frederik Teilfeldt Hansen, Teis Esben Søndergaard, Dan Stærk, T. Verne Lee, Reinhard Wimmer, Louise Graabæk Klitgaard, Stig Purup, Henriette Giese, Rasmus John Normand Frandsen

50 Citations (Scopus)

Abstract

Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F.graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.

Original language	English
Journal	Environmental Microbiology
Volume	14
Issue number	5
Pages (from-to)	1159-1170
Number of pages	12
ISSN	1462-2912
DOIs	https://doi.org/10.1111/j.1462-2920.2011.02696.x
Publication status	Published - May 2012

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10.1111/j.1462-2920.2011.02696.x

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title = "Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum",

abstract = "Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F.graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.",

author = "S{\o}rensen, {Jens Laurids} and Hansen, {Frederik Teilfeldt} and S{\o}ndergaard, {Teis Esben} and Dan St{\ae}rk and Lee, {T. Verne} and Reinhard Wimmer and Klitgaard, {Louise Graab{\ae}k} and Stig Purup and Henriette Giese and Frandsen, {Rasmus John Normand}",

year = "2012",

month = may,

doi = "10.1111/j.1462-2920.2011.02696.x",

language = "English",

volume = "14",

pages = "1159--1170",

journal = "Environmental Microbiology",

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T1 - Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum

AU - Sørensen, Jens Laurids

AU - Hansen, Frederik Teilfeldt

AU - Søndergaard, Teis Esben

AU - Stærk, Dan

AU - Lee, T. Verne

AU - Wimmer, Reinhard

AU - Klitgaard, Louise Graabæk

AU - Purup, Stig

AU - Giese, Henriette

AU - Frandsen, Rasmus John Normand

PY - 2012/5

Y1 - 2012/5

N2 - Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F.graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.

AB - Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F.graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.

U2 - 10.1111/j.1462-2920.2011.02696.x

DO - 10.1111/j.1462-2920.2011.02696.x

M3 - Journal article

SN - 1462-2912

VL - 14

SP - 1159

EP - 1170

JO - Environmental Microbiology

JF - Environmental Microbiology

IS - 5

ER -

Production of novel fusarielins by ectopic activation of the polyketide synthase 9 cluster in Fusarium graminearum

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