Engineering Aspergillus nidulans for heterologous ent-kaurene and gamma-terpinene production

Kirsi Bromann, Mervi Toivari, Kaarina Viljanen, Laura Ruohonen, Tiina Nakari-Setälä

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

Terpenes are a large and varied group of natural products with a wide array of bioactivities and applications. The chemical production of industrially relevant terpenes can be expensive and time-consuming due to the structural complexity of these compounds. Here, we studied Aspergillus nidulans as a heterologous host for monoterpene and diterpene production. Previously, we identified a novel diterpene gene cluster in A. nidulans and showed that overexpression of the cluster-specific transcription factor (pbcR) led to ent-pimara-8(14),15-diene (PD) production. We report further characterization of the A. nidulans PD synthase gene (pbcA). In A. nidulans, overexpression of pbcA resulted in PD production, while deletion of pbcA abolished PD production. Overexpression of Fusarium fujikuroi ent-kaurene synthase (cps/ks) and Citrus unshiu gamma-terpinene synthase resulted in ent-kaurene and gamma-terpinene production, respectively. A. nidulans is a fungal model organism and a close relative to other industrially relevant Aspergillus species. A. nidulans is a known producer of many secondary metabolites, but its ability to produce heterologous monoterpene and diterpene compounds has not been characterized. Here, we show that A. nidulans is capable of heterologous terpene production and thus has potential as a production host for industrially relevant compounds. The genetic engineering principles reported here could also be applied to other Aspergilli.

Original languageEnglish
Pages (from-to)6345-6359
Number of pages15
JournalApplied Microbiology and Biotechnology
Volume100
Issue number14
DOIs
Publication statusPublished - 1 Jul 2016
MoE publication typeA1 Journal article-refereed

Fingerprint

Kaurane Diterpenes
Aspergillus nidulans
Diterpenes
Terpenes
Monoterpenes
Aspergillus
Genetic Engineering
Citrus
Fusarium
Multigene Family
gamma-terpinene
Biological Products
Transcription Factors

Keywords

  • Aspergillus nidulans
  • ent-kaurene
  • ent-pimara-8(14),15-diene
  • Gamma-terpinene
  • Terpenoids

Cite this

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title = "Engineering Aspergillus nidulans for heterologous ent-kaurene and gamma-terpinene production",
abstract = "Terpenes are a large and varied group of natural products with a wide array of bioactivities and applications. The chemical production of industrially relevant terpenes can be expensive and time-consuming due to the structural complexity of these compounds. Here, we studied Aspergillus nidulans as a heterologous host for monoterpene and diterpene production. Previously, we identified a novel diterpene gene cluster in A. nidulans and showed that overexpression of the cluster-specific transcription factor (pbcR) led to ent-pimara-8(14),15-diene (PD) production. We report further characterization of the A. nidulans PD synthase gene (pbcA). In A. nidulans, overexpression of pbcA resulted in PD production, while deletion of pbcA abolished PD production. Overexpression of Fusarium fujikuroi ent-kaurene synthase (cps/ks) and Citrus unshiu gamma-terpinene synthase resulted in ent-kaurene and gamma-terpinene production, respectively. A. nidulans is a fungal model organism and a close relative to other industrially relevant Aspergillus species. A. nidulans is a known producer of many secondary metabolites, but its ability to produce heterologous monoterpene and diterpene compounds has not been characterized. Here, we show that A. nidulans is capable of heterologous terpene production and thus has potential as a production host for industrially relevant compounds. The genetic engineering principles reported here could also be applied to other Aspergilli.",
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Engineering Aspergillus nidulans for heterologous ent-kaurene and gamma-terpinene production. / Bromann, Kirsi; Toivari, Mervi; Viljanen, Kaarina; Ruohonen, Laura; Nakari-Setälä, Tiina.

In: Applied Microbiology and Biotechnology, Vol. 100, No. 14, 01.07.2016, p. 6345-6359.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Engineering Aspergillus nidulans for heterologous ent-kaurene and gamma-terpinene production

AU - Bromann, Kirsi

AU - Toivari, Mervi

AU - Viljanen, Kaarina

AU - Ruohonen, Laura

AU - Nakari-Setälä, Tiina

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Terpenes are a large and varied group of natural products with a wide array of bioactivities and applications. The chemical production of industrially relevant terpenes can be expensive and time-consuming due to the structural complexity of these compounds. Here, we studied Aspergillus nidulans as a heterologous host for monoterpene and diterpene production. Previously, we identified a novel diterpene gene cluster in A. nidulans and showed that overexpression of the cluster-specific transcription factor (pbcR) led to ent-pimara-8(14),15-diene (PD) production. We report further characterization of the A. nidulans PD synthase gene (pbcA). In A. nidulans, overexpression of pbcA resulted in PD production, while deletion of pbcA abolished PD production. Overexpression of Fusarium fujikuroi ent-kaurene synthase (cps/ks) and Citrus unshiu gamma-terpinene synthase resulted in ent-kaurene and gamma-terpinene production, respectively. A. nidulans is a fungal model organism and a close relative to other industrially relevant Aspergillus species. A. nidulans is a known producer of many secondary metabolites, but its ability to produce heterologous monoterpene and diterpene compounds has not been characterized. Here, we show that A. nidulans is capable of heterologous terpene production and thus has potential as a production host for industrially relevant compounds. The genetic engineering principles reported here could also be applied to other Aspergilli.

AB - Terpenes are a large and varied group of natural products with a wide array of bioactivities and applications. The chemical production of industrially relevant terpenes can be expensive and time-consuming due to the structural complexity of these compounds. Here, we studied Aspergillus nidulans as a heterologous host for monoterpene and diterpene production. Previously, we identified a novel diterpene gene cluster in A. nidulans and showed that overexpression of the cluster-specific transcription factor (pbcR) led to ent-pimara-8(14),15-diene (PD) production. We report further characterization of the A. nidulans PD synthase gene (pbcA). In A. nidulans, overexpression of pbcA resulted in PD production, while deletion of pbcA abolished PD production. Overexpression of Fusarium fujikuroi ent-kaurene synthase (cps/ks) and Citrus unshiu gamma-terpinene synthase resulted in ent-kaurene and gamma-terpinene production, respectively. A. nidulans is a fungal model organism and a close relative to other industrially relevant Aspergillus species. A. nidulans is a known producer of many secondary metabolites, but its ability to produce heterologous monoterpene and diterpene compounds has not been characterized. Here, we show that A. nidulans is capable of heterologous terpene production and thus has potential as a production host for industrially relevant compounds. The genetic engineering principles reported here could also be applied to other Aspergilli.

KW - Aspergillus nidulans

KW - ent-kaurene

KW - ent-pimara-8(14),15-diene

KW - Gamma-terpinene

KW - Terpenoids

U2 - 10.1007/s00253-016-7517-5

DO - 10.1007/s00253-016-7517-5

M3 - Article

C2 - 27098256

AN - SCOPUS:85028278684

VL - 100

SP - 6345

EP - 6359

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

IS - 14

ER -