Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum

Heng Chooi, R. Cacho, Y. Tang

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed that two nonreducing PKSs (NRPKSs), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, because deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways. © 2010 Elsevier Ltd All rights reserved.
Original languageEnglish
Pages (from-to)483-494
JournalChemistry and Biology
Volume17
Issue number5
DOIs
Publication statusPublished - 2010

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Polyketides
Griseofulvin
Antifungal Agents
Penicillium
Gene Deletion
Firearms
Multigene Family
Tetracycline
Molecular Biology
Genes
Chromosomes
Biosynthesis
Genome
viridicatumtoxin

Cite this

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title = "Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum",
abstract = "Penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed that two nonreducing PKSs (NRPKSs), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, because deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways. {\circledC} 2010 Elsevier Ltd All rights reserved.",
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Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum. / Chooi, Heng; Cacho, R.; Tang, Y.

In: Chemistry and Biology, Vol. 17, No. 5, 2010, p. 483-494.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum

AU - Chooi, Heng

AU - Cacho, R.

AU - Tang, Y.

PY - 2010

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N2 - Penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed that two nonreducing PKSs (NRPKSs), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, because deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways. © 2010 Elsevier Ltd All rights reserved.

AB - Penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed that two nonreducing PKSs (NRPKSs), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, because deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways. © 2010 Elsevier Ltd All rights reserved.

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