Functional Analysis of the Cyclopiazonic Acid Biosynthesis Gene Cluster in<i>Aspergillus oryzae</i>RIB 40

Shinohara, Yasutomo; Tokuoka, Masafumi; Koyama, Yasuji

doi:10.1271/bbb.110467

Cited by 16 publications

(9 citation statements)

References 10 publications

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“…Inactivation of these three genes resulted in loss of CPA production. Orthologous genes ( cpaD = dmtA ; cpaA = pks-nrps ; cpaO = moaA ) have been identified in A. oryzae and also shown, by gene disruption, to be required for biosynthesis of CPA ( Shinohara et al, 2011 ). Interestingly, the CPA cluster in both of these fungi also contained a putative transcription factor ( cpaR = ctfR1 ), however, disruption of this gene in both A. flavus and A. oryzae did not affect CPA production.…”

Section: Gene Clusters Producing Secondary Metabolites Associated Witmentioning

confidence: 99%

“…In the initial step in CPA biosynthesis, the PKS-NRPS catalyzes the condensation of L -tryptophan and two molecules of acetyl-CoA to generate cycloacetoacetyl- L -tryptophan (cAATrp) which is then converted by the DMAT to β-CPA. The FAD-dependent oxidoreductase is then responsible for the cyclization of β-CPA to CPA ( Shinohara et al, 2011 ). Interestingly, A. oryzae RIB40, which does not make CPA, was found to have a truncated version of the PKS-NRPS ( cpaA ) gene.…”

Section: Gene Clusters Producing Secondary Metabolites Associated Witmentioning

confidence: 99%

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Association of fungal secondary metabolism and sclerotial biology

2015

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Fungal secondary metabolism and morphological development have been shown to be intimately associated at the genetic level. Much of the literature has focused on the co-regulation of secondary metabolite production (e.g., sterigmatocystin and aflatoxin in Aspergillus nidulans and Aspergillus flavus, respectively) with conidiation or formation of sexual fruiting bodies. However, many of these genetic links also control sclerotial production. Sclerotia are resistant structures produced by a number of fungal genera. They also represent the principal source of primary inoculum for some phytopathogenic fungi. In nature, higher plants often concentrate secondary metabolites in reproductive structures as a means of defense against herbivores and insects. By analogy, fungi also sequester a number of secondary metabolites in sclerotia that act as a chemical defense system against fungivorous predators. These include antiinsectant compounds such as tetramic acids, indole diterpenoids, pyridones, and diketopiperazines. This chapter will focus on the molecular mechanisms governing production of secondary metabolites and the role they play in sclerotial development and fungal ecology, with particular emphasis on Aspergillus species. The global regulatory proteins VeA and LaeA, components of the velvet nuclear protein complex, serve as virulence factors and control both development and secondary metabolite production in many Aspergillus species. We will discuss a number of VeA- and LaeA-regulated secondary metabolic gene clusters in A. flavus that are postulated to be involved in sclerotial morphogenesis and chemical defense. The presence of multiple regulatory factors that control secondary metabolism and sclerotial formation suggests that fungi have evolved these complex regulatory mechanisms as a means to rapidly adapt chemical responses to protect sclerotia from predators, competitors and other environmental stressors.

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Section: Gene Clusters Producing Secondary Metabolites Associated Witmentioning

confidence: 99%

Section: Gene Clusters Producing Secondary Metabolites Associated Witmentioning

confidence: 99%

Association of fungal secondary metabolism and sclerotial biology

2015

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“…Comparison of the cpa gene cluster of the CPA producer A. oryzae NBRC 4177 with that of the non‐producing strain A. oryzae RIB40 revealed deletion of one half of the cpaS gene through telomeric replacement in RIB40 (Figure 1). 88 However, stable‐isotope‐labeling experiments for RIB40 with the CpaS product cAATrp led to the production of 2‐oxo‐CPA and proved that the remaining genes of the cluster, cpaD and cpaO , were still functional. Further conversion of CPA into the less toxic 2‐oxo‐CPA is catalyzed by the putative P450 enzyme CpaH (Scheme ) 88.…”

Section: Cyclopiazonic Acidmentioning

confidence: 99%

“…88 However, stable‐isotope‐labeling experiments for RIB40 with the CpaS product cAATrp led to the production of 2‐oxo‐CPA and proved that the remaining genes of the cluster, cpaD and cpaO , were still functional. Further conversion of CPA into the less toxic 2‐oxo‐CPA is catalyzed by the putative P450 enzyme CpaH (Scheme ) 88. Surprisingly, this additional enzymatic activity is not present in the cpa clusters of toxic CPA‐producing species like A. flavus (Figure 1).…”

Section: Cyclopiazonic Acidmentioning

confidence: 99%

Molecular Diversity Sculpted by Fungal PKS–NRPS Hybrids

2012

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Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids manufacture a wide range of structurally diverse secondary metabolites that play an eminent role in the environment, as molecular tools and leads for therapeutic development. To date, a dozen PKS-NRPS megasynthetases can be linked to the corresponding secondary metabolites, which stand out because of their structural complexity. The diversity of their structures, biological activities, and biosynthetic routes are particularly intriguing considering the iterative use of the catalytic domains of the biosynthetic enzymes-implying an enigmatic biosynthetic code. This review provides an overview of the characterized fungal PKS-NRPS hybrids, their manifold functionalities, and the diversity of the resulting secondary metabolites, as well as molecular engineering attempts that highly improved the understanding of their cryptic programming.

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“…In A. flavus , the CPA biosynthetic pathway consisted of 3 genes (cpaS, cpaD, and cpaO) and was situated next to the AF biosynthesis gene cluster (Chang and others ). In A. oryzae , the ability to form CPA is strain‐dependent (Chang and others ); while the cluster is complete in the NBRC 4177 strain, the RIB40 strain is unable to form the mycotoxin due to a truncation of the PKS–NRPS (Shinohara and others ). Studies performed by Liu and Walsh (, ) demonstrated that cpaS encodes a PKS–NRPS responsible for cAATrp formation, while cpaD encodes a cAATrp‐dimethylallyltransferase, leading to β ‐CPA.…”

Section: Mycotoxin Biosynthetic Pathwaysmentioning

confidence: 99%

Filamentous Fungi and Mycotoxins in Cheese: A Review

Hymery

Vasseur

Coton

et al. 2014

Comp Rev Food Sci Food Safe

162

111

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Important fungi growing on cheese include Penicillium, Aspergillus, Cladosporium, Geotrichum, Mucor, and Trichoderma. For some cheeses, such as Camembert, Roquefort, molds are intentionally added. However, some contaminating or technological fungal species have the potential to produce undesirable metabolites such as mycotoxins. The most hazardous mycotoxins found in cheese, ochratoxin A and aflatoxin M1, are produced by unwanted fungal species either via direct cheese contamination or indirect milk contamination (animal feed contamination), respectively. To date, no human food poisoning cases have been associated with contaminated cheese consumption. However, although some studies state that cheese is an unfavorable matrix for mycotoxin production; these metabolites are actually detected in cheeses at various concentrations. In this context, questions can be raised concerning mycotoxin production in cheese, the biotic and abiotic factors influencing their production, mycotoxin relative toxicity as well as the methods used for detection and quantification. This review emphasizes future challenges that need to be addressed by the scientific community, fungal culture manufacturers, and artisanal and industrial cheese producers.

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Functional Analysis of the Cyclopiazonic Acid Biosynthesis Gene Cluster inAspergillus oryzaeRIB 40

Cited by 16 publications

References 10 publications

Association of fungal secondary metabolism and sclerotial biology

Association of fungal secondary metabolism and sclerotial biology

Molecular Diversity Sculpted by Fungal PKS–NRPS Hybrids

Filamentous Fungi and Mycotoxins in Cheese: A Review

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