Recent advances on the molecular aspects of ochratoxin A biosynthesis

Gallo, Antonia; Ferrara, Massimo; Perrone, Giancarlo

doi:10.1016/j.cofs.2017.09.011

Cited by 41 publications

(31 citation statements)

References 42 publications

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“…The second regulator found in OTA cluster, ota R2, can modulate the expression of otaA, otaC and otaD but did not regulate the expression of otaB, otaE or otaR1. In A. carbonarius, toward the edges of the OTA cluster, two genes encoding transcription factors have been described (Gallo et al, 2017). These transcription factors (ID 173470, ID 132614) contain Cys -rich motives which are present in zinc-cluster proteins (Zn2Cys6), the most common regulators of fungal secondary metabolism (Brakhage, 2013).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of non-ochratoxigenic Aspergillus carbonarius strains and interactions between some black aspergilli species

Castellá

Bragulat

Cigliano

et al. 2020

International Journal of Food Microbiology

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Aspergillus carbonarius consistently produces large amounts of ochratoxin A (OTA), a mycotoxin with nephrotoxic effects on animals and humans. In the present study, we analyzed the transcriptional changes associated to OTA production in three atypical non-ochratoxigenic strains of A. carbonarius. In addition, in vitro interactions between ochratoxigenic strains of A. carbonarius and A. niger and non-ochratoxigenic strains of A. carbonarius and A. tubingensis were studied in order to evaluate their potential for controlling OTA production. RNA-seq analysis revealed that there are 696 differentially expressed genes identified in the three non-OTA producing strains, including 280 upregulated and 333 down-regulated genes. A functional and gene ontology enrichment analysis revealed that the processes related to metabolic and oxidation processes, associated with functions such oxidoreductase and hydrolase activity were down regulated. All the genes related with OTA biosynthesis in A. carbonarius were the most down-regulated genes in non-ochratoxigenic strains. We also showed that these strains possess a deleterious mutation in the AcOTApks gene required for OTA biosynthesis. Moreover, one of these strains gave the best control of OTA production resulting in an OTA reduction of 98-100% in co-inoculation with an ochratoxigenic strain of A. niger and an OTA reduction of 79-89% with an ochratoxigenic strain of A. carbonarius. Results of this study provided novel insights into the knowledge of the OTA biosynthetic pathway in these non-ochratoxigenic wild strains, and showed the biocontrol potential of these strains.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of non-ochratoxigenic Aspergillus carbonarius strains and interactions between some black aspergilli species

Castellá

Bragulat

Cigliano

et al. 2020

International Journal of Food Microbiology

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“…Ochratoxin A (OTA) is a mycotoxin that is a common contaminant of a wide variety of food products. The molecular structure comprises a chlorinated polyketide dihydroisocoumarin ring linked to phenylalanine and, as shown in different producing fungal species, a polyketide synthase (PKS) is a major part of the biosynthetic pathway (Wang et al 2016 ; Massi et al 2016 ; Gallo et al 2017 ; Gill-Serna et al 2018 ). OTA inhibits protein synthesis and energy production, induces oxidative stress, cell apoptosis and necrosis, and DNA adduct formation, and is mostly recognized as a nephrotoxin (Heussner and Bingle 2015 ; Közégi and Poór 2016 ).…”

Section: Mycotoxins Are a Very Limited Group Of Fungal Secondary Metamentioning

confidence: 99%

Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei

Frisvad

Møller

Larsen

et al. 2018

Appl Microbiol Biotechnol

256

269

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This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin producer, due to misclassification of Aspergillus flavus strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.

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“…Farber and Geisen demonstrated the potential role of a putative halogenase through the analysis of differentially expressed OTA biosynthesis genes in Penicillium nordicum (15), and Ferrara et al identified a halogenase involved in OTA biosynthesis in A. carbonarius (16). However, the details of the OTA biosynthetic pathway remained unclear and its regulatory mechanism unknown (10,17,18).…”

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confidence: 99%

A Consensus Ochratoxin A Biosynthetic Pathway: Insights from the Genome Sequence of Aspergillus ochraceus and a Comparative Genomic Analysis

Wang

et al. 2018

Appl Environ Microbiol

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Ochratoxin A (OTA) is a toxic secondary metabolite produced by and species that widely contaminate food and feed. We sequenced and assembled the complete ∼37 Mb genome of fc-1, a well-known producer of OTA. Key genes of the OTA biosynthetic pathway were identified by comparative genomic analyses with five other sequenced OTA-producing fungi,, ,, , and OTA production was completely inhibited in the deletion mutants (- and ), and OTA biosynthesis was restored by feeding a post-block substrate to the corresponding mutant. The OTA biosynthetic pathway was unblocked with the addition of heterologously expressed halogenase in the mutant. OTA biosynthesis begins with PKS (), utilizing acetyl-CoA and malonyl-CoA to synthesize 7-methylmellein, which is oxidized to OTβ by cytochrome P450 monooxygenase (). OTβ and L-β-phenylalanine are combined by NRPS () to form an amide bond to synthesize OTB. Finally, OTB is chlorinated by halogenase () to OTA. The - genes were expressed at low levels in the mutant. A second regulator, otaR2, which is adjacent to the biosynthetic gene, could modulate only the expression of, and Thus, we have identified a consensus OTA biosynthetic pathway that can be used to prevent and control OTA synthesis, and to understand variation and production of the intermediate components in the biosynthetic pathway. Ochratoxin A (OTA) is a significant mycotoxin that contaminates cereal products, coffee, grapes, wine, cheese and meat. OTA is nephrotoxic, carcinogenic, teratogenic and immunotoxic. OTA contamination is a serious threat to food safety, endangers human health and can cause huge economic losses. At present, more than 20 species of the genera and are known to produce OTA. Here, we demonstrate that a consensus OTA biosynthetic pathway exists in all OTA-producing fungi and that is encoded by a gene cluster containing four highly conserved biosynthetic genes and a bZIP transcription factor.

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Recent advances on the molecular aspects of ochratoxin A biosynthesis

Cited by 41 publications

References 42 publications

Transcriptome analysis of non-ochratoxigenic Aspergillus carbonarius strains and interactions between some black aspergilli species

Transcriptome analysis of non-ochratoxigenic Aspergillus carbonarius strains and interactions between some black aspergilli species

Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei

A Consensus Ochratoxin A Biosynthetic Pathway: Insights from the Genome Sequence of Aspergillus ochraceus and a Comparative Genomic Analysis

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