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Toxins
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Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the...
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Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (30 June 2018) | Viewed by 40908

Special Issue Editors

Dr. Giancarlo Perrone

E-Mail Website
Guest Editor
CNR-ISPA (National Research Council-Institute of Sciences of Food Production), Via G. Amendola 122/O, 70126 Bari, Italy
Interests: food mycology; phylogeny; taxonomy; morphology; ecology and genomics of Aspergillus and Penicillium toxigenic species
Special Issues, Collections and Topics in MDPI journals
Dr. Antonia Gallo

E-Mail Website
Guest Editor
Institute of Sciences of Food Production, National Research Council, Via Provinciale Lecce-Monteroni, 73100 Lecce, Italy
Interests: fungal secondary metabolism; mycotoxins; molecular biology; genomics; transcriptomics; regulatory mechanisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The occurrence of fungal species, able to produce toxic metabolites, in agro-food products has received increasing attention over the last few decades. These metabolites, known as mycotoxins, are generally of low molecular weight, may have toxic activity toward plants, but they principally represent a serious risk for human and animal health. In the 1990s, fungal secondary metabolites (SMs), such as antibiotics and mycotoxins, started to be genetically characterized. In the pre-genomic era, the clustered arrangement of genes involved in the biosynthesis of a single SM was studied by means of cumbersome and traditional molecular methods. The breakthrough of next-generation sequencing (NGS) technologies, and the advent of Bioinformatics and Genomics, have revolutionized research on SM biosynthesis pathways. However, a great deal remains to be clarified in order to completely explain the pathway steps and the regulatory network behind metabolite biosynthesis. More recently, genomic, transcriptomic, proteomic, and metabolomic tools, applied to fungal biology, have provided new data for understanding the ecology of toxigenic fungi in the field and crops, and the process of mycotoxin production and contamination under various environmental conditions. These current technologies of functional genomics have the potential to reveal the molecular mechanisms of response to climate change, as well as abiotic regulation of the secondary metabolites production and influence on the plant–fungus interactions.

This Special Issue of Toxins wishes to present the most recent data on the main aspects of functional genomics of toxigenic fungi and regulatory mechanisms in the biosynthesis of mycotoxins, with the aim of better understanding the eco-physiology of mycotoxin production, and to get a view of predicting changes in fungal infections and toxin production associated with new climate scenarios.

Dr. Giancarlo Perrone
Dr. Antonia Gallo
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mycotoxigenic fungi
  • secondary metabolites
  • fungal genomics
  • fungal transcriptomics
  • fungal metabolomics
  • biosynthesis gene cluster
  • regulatory pathway
  • transcription factors
  • stress induction
  • signal transduction

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Published Papers (5 papers)

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Research

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17 pages, 2922 KiB  
Article
The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in Aspergillus flavus by Modulating Transcription Factors FarB and CreA
by Xixi Zhao, Qing-Qing Zhi, Jie-Ying Li, Nancy P. Keller and Zhu-Mei He
Toxins 2018, 10(7), 270; https://doi.org/10.3390/toxins10070270 - 3 Jul 2018
Cited by 69 | Viewed by 6631
Abstract
Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in Aspergillus flavus in a dose-dependent manner. [...] Read more.
Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in Aspergillus flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid-treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β-oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene, creA, was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis, and aflatoxin biosynthesis genes were significantly downregulated in ∆creA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus. Full article
(This article belongs to the Special Issue Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins)
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16 pages, 5350 KiB  
Article
Functional Characterization of the alb1 Orthologue Gene in the Ochratoxigenic Fungus Aspergillus carbonarius (AC49 strain)
by Donato Gerin, Luis González-Candelas, Ana-Rosa Ballester, Stefania Pollastro, Rita Milvia De Miccolis Angelini and Francesco Faretra
Toxins 2018, 10(3), 120; https://doi.org/10.3390/toxins10030120 - 12 Mar 2018
Cited by 9 | Viewed by 5643
Abstract
Aspergillus carbonarius, belonging to the group Nigri, is the main species responsible for contamination by ochratoxin A (OTA) in grapes and derivative products. OTA can accumulate in the mycelium and in black conidia of the fungus and released into the matrix. Here, [...] Read more.
Aspergillus carbonarius, belonging to the group Nigri, is the main species responsible for contamination by ochratoxin A (OTA) in grapes and derivative products. OTA can accumulate in the mycelium and in black conidia of the fungus and released into the matrix. Here, we have deleted in A. carbonarius the alb1 orthologue gene of A. fumigatus, involved in melanin biosynthesis. Three A. carbonarius Δalb1 mutants were characterized for morphologic traits and OTA production on different media and temperatures. Δalb1 mutants showed a fawn color of conidia associated with a significant reduction of the conidiogenesis and a statistically significant increase (p ≤ 0.01) of total OTA production as compared to the wild type (WT) strain. The alb1 gene somehow affected OTA partitioning since in Δalb1 mutants OTA amount was lower in conidia and was more abundantly secreted into the medium as compared to the WT. On grape berries the Δalb1 mutants and the WT caused lesions with similar sizes but OTA amount in berry tissues was higher for the mutants. These results demonstrate that A. carbonarius conidia pigmentation is largely dependent on polyketide biosynthesis. The gene is not directly involved in virulence and its deletion affects morphological features and OTA production in the fungus. Full article
(This article belongs to the Special Issue Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins)
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16 pages, 3244 KiB  
Article
Activation of Aflatoxin Biosynthesis Alleviates Total ROS in Aspergillus parasiticus
by Gabriel J. Kenne, Phani M. Gummadidala, Mayomi H. Omebeyinje, Ananda M. Mondal, Dominic K. Bett, Sandra McFadden, Sydney Bromfield, Nora Banaszek, Michelle Velez-Martinez, Chandrani Mitra, Isabelle Mikell, Saurabh Chatterjee, Josephine Wee and Anindya Chanda
Toxins 2018, 10(2), 57; https://doi.org/10.3390/toxins10020057 - 29 Jan 2018
Cited by 35 | Viewed by 6815
Abstract
An aspect of mycotoxin biosynthesis that remains unclear is its relationship with the cellular management of reactive oxygen species (ROS). Here we conduct a comparative study of the total ROS production in the wild-type strain (SU-1) of the plant pathogen and aflatoxin producer, [...] Read more.
An aspect of mycotoxin biosynthesis that remains unclear is its relationship with the cellular management of reactive oxygen species (ROS). Here we conduct a comparative study of the total ROS production in the wild-type strain (SU-1) of the plant pathogen and aflatoxin producer, Aspergillus parasiticus, and its mutant strain, AFS10, in which the aflatoxin biosynthesis pathway is blocked by disruption of its pathway regulator, aflR. We show that SU-1 demonstrates a significantly faster decrease in total ROS than AFS10 between 24 h to 48 h, a time window within which aflatoxin synthesis is activated and reaches peak levels in SU-1. The impact of aflatoxin synthesis in alleviation of ROS correlated well with the transcriptional activation of five superoxide dismutases (SOD), a group of enzymes that protect cells from elevated levels of a class of ROS, the superoxide radicals (O2−). Finally, we show that aflatoxin supplementation to AFS10 growth medium results in a significant reduction of total ROS only in 24 h cultures, without resulting in significant changes in SOD gene expression. Our findings show that the activation of aflatoxin biosynthesis in A. parasiticus alleviates ROS generation, which in turn, can be both aflR dependent and aflatoxin dependent. Full article
(This article belongs to the Special Issue Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins)
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4263 KiB  
Article
The Aspergillus flavus Homeobox Gene, hbx1, Is Required for Development and Aflatoxin Production
by Jeffrey W. Cary, Pamela Harris-Coward, Leslie Scharfenstein, Brian M. Mack, Perng-Kuang Chang, Qijian Wei, Matthew Lebar, Carol Carter-Wientjes, Rajtilak Majumdar, Chandrani Mitra, Sourav Banerjee and Anindya Chanda
Toxins 2017, 9(10), 315; https://doi.org/10.3390/toxins9100315 - 12 Oct 2017
Cited by 37 | Viewed by 9435
Abstract
Homeobox proteins, a class of well conserved transcription factors, regulate the expression of targeted genes, especially those involved in development. In filamentous fungi, homeobox genes are required for normal conidiogenesis and fruiting body formation. In the present study, we identified eight homeobox ( [...] Read more.
Homeobox proteins, a class of well conserved transcription factors, regulate the expression of targeted genes, especially those involved in development. In filamentous fungi, homeobox genes are required for normal conidiogenesis and fruiting body formation. In the present study, we identified eight homeobox (hbx) genes in the aflatoxin-producing ascomycete, Aspergillus flavus, and determined their respective role in growth, conidiation and sclerotial production. Disruption of seven of the eight genes had little to no effect on fungal growth and development. However, disruption of the homeobox gene AFLA_069100, designated as hbx1, in two morphologically different A. flavus strains, CA14 and AF70, resulted in complete loss of production of conidia and sclerotia as well as aflatoxins B1 and B2, cyclopiazonic acid and aflatrem. Microscopic examination showed that the Δhbx1 mutants did not produce conidiophores. The inability of Δhbx1 mutants to produce conidia was related to downregulation of brlA (bristle) and abaA (abacus), regulatory genes for conidiophore development. These mutants also had significant downregulation of the aflatoxin pathway biosynthetic genes aflC, aflD, aflM and the cluster-specific regulatory gene, aflR. Our results demonstrate that hbx1 not only plays a significant role in controlling A. flavus development but is also critical for the production of secondary metabolites, such as aflatoxins. Full article
(This article belongs to the Special Issue Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins)
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Review

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19 pages, 2346 KiB  
Review
Fungal Cytochrome P450s and the P450 Complement (CYPome) of Fusarium graminearum
by Jiyoung Shin, Jung-Eun Kim, Yin-Won Lee and Hokyoung Son
Toxins 2018, 10(3), 112; https://doi.org/10.3390/toxins10030112 - 7 Mar 2018
Cited by 110 | Viewed by 11531
Abstract
Cytochrome P450s (CYPs), heme-containing monooxygenases, play important roles in a wide variety of metabolic processes important for development as well as biotic/trophic interactions in most living organisms. Functions of some CYP enzymes are similar across organisms, but some are organism-specific; they are involved [...] Read more.
Cytochrome P450s (CYPs), heme-containing monooxygenases, play important roles in a wide variety of metabolic processes important for development as well as biotic/trophic interactions in most living organisms. Functions of some CYP enzymes are similar across organisms, but some are organism-specific; they are involved in the biosynthesis of structural components, signaling networks, secondary metabolisms, and xenobiotic/drug detoxification. Fungi possess more diverse CYP families than plants, animals, or bacteria. Various fungal CYPs are involved in not only ergosterol synthesis and virulence but also in the production of a wide array of secondary metabolites, which exert toxic effects on humans and other animals. Although few studies have investigated the functions of fungal CYPs, a recent systematic functional analysis of CYP genes in the plant pathogen Fusarium graminearum identified several novel CYPs specifically involved in virulence, asexual and sexual development, and degradation of xenobiotics. This review provides fundamental information on fungal CYPs and a new platform for further metabolomic and biochemical studies of CYPs in toxigenic fungi. Full article
(This article belongs to the Special Issue Functional Genomics of Toxigenic Fungi and Regulatory Mechanism in the Biosynthesis of Mycotoxins)
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