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Molecular Biology and Chemistry of Mycotoxins and Phytotoxins 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 6843

Special Issue Editors

Department of Biological Mechanisms and Function, Graduate School of Bioagricultural Sciences, Nagoya University, Furo‐cho, Chikusa‐ku, Nagoya, Aichi 464‐8601, Japan
Interests: fungal molecular biology; mycotoxin biosynthesis and regulation; secondary metabolism; plant-pathogen interaction; gene expression
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Guest Editor
INRAE, UR 1264 MycSA Mycologie et Sécurité des Aliments, Centre de recherche Nouvelle-Aquitaine-Bordeaux, Villenave D’Ornon, France
Interests: mycotoxins; toxigenic fungi; Fusarium mycotoxins; Fusarium species; production of mycotoxins; biosynthesis of mycotoxins
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Plant Pathology Laboratory, Graduate School of Bioagrocultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Interests: plant-microbe interactions; pathogenicity; symbiosis

Special Issue Information

Dear Colleagues, 

Many filamentous fungi can grow on pre- or post-harvest crops under favorable growth conditions, either parasitically or saprophytically. In this process, they often produce secondary metabolites with ecological significance. Such small molecules were traditionally termed as mycotoxins (fungal toxins active toward animals) and phytotoxins (fungal toxins active toward plants); however, it is now evident that this categorization does not appropriately represent the nature of the toxic chemicals. For example, fumonisins and AAL-toxins (host-specific toxins) are mycotoxins and phytotoxins, respectively, and yet they share the same polyketide backbone and biological activity. Trichothecene mycotoxins contribute to plant disease development and play minor roles as phytotoxins. Biosynthesis genes of toxins involved in biological interactions tend to evolve extensively and generate structural diversity of the toxin side-chains.

This Special Issue, “Molecular Biology and Chemistry of Mycotoxins and Phytotoxins,” deals with the various aspects of fungal toxins potentially involved in the survival of the producers in their ecological niche. The scope of this Issue includes but is not limited to:  

  • Biosynthesis of fungal secondary metabolites with ecological significance
  • Structural diversity of fungal toxins, such as trichothecenes and fumonisins
  • Regulation of fungal toxin gene expression
  • Plant, microbial, and animal responses to toxigenic fungi and toxins

We wholeheartedly welcome both original research articles and reviews on fungal toxins.

Dr. Makoto Kimura
Dr. Florence Richard-Forget
Dr. Daigo Takemoto
Guest Editors

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Published Papers (14 papers)

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23 pages, 2422 KiB  
Article
4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers
by Kosuke Matsui, Hirone Takeda, Koki Shinkai, Takao Kakinuma, Yoshiaki Koizumi, Masahiro Kase, Tomoya Yoshinari, Hiroaki Minegishi, Yuichi Nakajima, Shunichi Aikawa, Naoko Takahashi-Ando and Makoto Kimura
Int. J. Mol. Sci. 2021, 22(24), 13542; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413542 - 17 Dec 2021
Cited by 5 | Viewed by 2880
Abstract
The t-type trichothecene producers Fusarium sporotrichioides and Fusarium graminearum protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δtri5 mutants expressing all [...] Read more.
The t-type trichothecene producers Fusarium sporotrichioides and Fusarium graminearum protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δtri5 mutants expressing all but the first trichothecene pathway enzymes were fed with trichodermol (TDmol), trichothecolone (TCC), 8-deoxytrichothecin, and trichothecin. LC-MS/MS and NMR analyses showed that these C-3 unoxygenated trichothecenes were conjugated with glucose at C-4 by α-glucosidic linkage. As t-type trichothecenes are readily incorporated into the biosynthetic pathway following the C-3 acetylation, the mycotoxins were fed to the ΔFgtri5ΔFgtri101 mutant to examine their fate. LC-MS/MS and NMR analyses demonstrated that the mutant conjugated glucose at C-4 of HT-2 toxin (HT-2) by α-glucosidic linkage, while the ΔFgtri5 mutant metabolized HT-2 to 3-acetyl HT-2 toxin and T-2 toxin. The 4-O-glucosylation of exogenously added t-type trichothecenes appears to be a general response of the ΔFgtri5ΔFgtri101 mutant, as nivalenol and its acetylated derivatives appeared to be conjugated with hexose to some extent. The toxicities of 4-O-glucosides of TDmol, TCC, and HT-2 were much weaker than their corresponding aglycons, suggesting that 4-O-glucosylation serves as a phase II xenobiotic metabolism for t-type trichothecene producers. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins 2.0)
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10 pages, 1902 KiB  
Communication
Accumulation of 4-Deoxy-7-hydroxytrichothecenes, but Not 4,7-Dihydroxytrichothecenes, in Axenic Culture of a Transgenic Nivalenol Chemotype Expressing the NX-Type FgTri1 Gene
by Kazuyuki Maeda, Yuichi Nakajima, Yoshiaki Koizumi, Naoko Takahashi-Ando, Makoto Kimura and Shuichi Ohsato
Int. J. Mol. Sci. 2021, 22(21), 11428; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111428 - 22 Oct 2021
Viewed by 1581
Abstract
Fusarium graminearum species complex produces type B trichothecenes oxygenated at C-7. In axenic liquid culture, F. graminearum mainly accumulates one of the three types of trichothecenes, namely 3-acetyldeoxyinvalenol, 15-acetyldeoxyinvalenol, or mixtures of 4,15-diacetylnivalenol/4-acetylnivalenol, depending on each strain’s genetic background. The acetyl groups of [...] Read more.
Fusarium graminearum species complex produces type B trichothecenes oxygenated at C-7. In axenic liquid culture, F. graminearum mainly accumulates one of the three types of trichothecenes, namely 3-acetyldeoxyinvalenol, 15-acetyldeoxyinvalenol, or mixtures of 4,15-diacetylnivalenol/4-acetylnivalenol, depending on each strain’s genetic background. The acetyl groups of these trichothecenes are slowly deacetylated to give deoxynivalenol (DON) or nivalenol (NIV) on solid medium culture. Due to the evolution of F. graminearum FgTri1, encoding a cytochrome P450 monooxygenase responsible for hydroxylation at both C-7 and C-8, new derivatives of DON, designated as NX-type trichothecenes, have recently emerged. To assess the risks of emergence of new NX-type trichothecenes, we examined the effects of replacing FgTri1 in the three chemotypes with FgTri1_NX chemotype, which encodes a cytochrome P450 monooxygenase that can only hydroxylate C-7 of trichothecenes. Similar to the transgenic DON chemotypes, the transgenic NIV chemotype strain accumulated NX-type 4-deoxytrichothecenes in axenic liquid culture. C-4 oxygenated trichothecenes were marginal, despite the presence of a functional FgTri13 encoding a C-4 hydroxylase. At present, outcrossing of the currently occurring NX chemotype with NIV chemotype strains of F. graminearum in the natural environment likely will not yield a new strain that produces a C-4 oxygenated NX-type trichothecene. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins 2.0)
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16 pages, 1561 KiB  
Article
Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells
by Anne-Margarethe Enge, Florian Kaltner, Christoph Gottschalk, Albert Braeuning and Stefanie Hessel-Pras
Int. J. Mol. Sci. 2021, 22(8), 3821; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083821 - 07 Apr 2021
Cited by 8 | Viewed by 2173
Abstract
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the [...] Read more.
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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13 pages, 1771 KiB  
Article
Nicotinamide Effectively Suppresses Fusarium Head Blight in Wheat Plants
by Yasir Sidiq, Masataka Nakano, Yumi Mori, Takashi Yaeno, Makoto Kimura and Takumi Nishiuchi
Int. J. Mol. Sci. 2021, 22(6), 2968; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062968 - 15 Mar 2021
Cited by 12 | Viewed by 3861
Abstract
Pyridine nucleotides such as a nicotinamide adenine dinucleotide (NAD) are known as plant defense activators. We previously reported that nicotinamide mononucleotide (NMN) enhanced disease resistance against fungal pathogen Fusarium graminearum in barley and Arabidopsis. In this study, we reveal that the pretreatment of [...] Read more.
Pyridine nucleotides such as a nicotinamide adenine dinucleotide (NAD) are known as plant defense activators. We previously reported that nicotinamide mononucleotide (NMN) enhanced disease resistance against fungal pathogen Fusarium graminearum in barley and Arabidopsis. In this study, we reveal that the pretreatment of nicotinamide (NIM), which does not contain nucleotides, effectively suppresses disease development of Fusarium Head Blight (FHB) in wheat plants. Correspondingly, deoxynivalenol (DON) mycotoxin accumulation was also significantly decreased by NIM pretreatment. A metabolome analysis showed that several antioxidant and antifungal compounds such as trigonelline were significantly accumulated in the NIM-pretreated spikes after inoculation of F. graminearum. In addition, some metabolites involved in the DNA hypomethylation were accumulated in the NIM-pretreated spikes. On the other hand, fungal metabolites DON and ergosterol peroxide were significantly reduced by the NIM pretreatment. Since NIM is relative stable and inexpensive compared with NMN and NAD, it may be more useful for the control of symptoms of FHB and DON accumulation in wheat and other crops. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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10 pages, 3898 KiB  
Article
Nicotinamide Mononucleotide Potentiates Resistance to Biotrophic Invasion of Fungal Pathogens in Barley
by Kana Ueda, Yuichi Nakajima, Hiroshi Inoue, Kappei Kobayashi, Takumi Nishiuchi, Makoto Kimura and Takashi Yaeno
Int. J. Mol. Sci. 2021, 22(5), 2696; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052696 - 07 Mar 2021
Cited by 4 | Viewed by 2721
Abstract
Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), induces disease resistance to the Fusarium head blight fungus Fusarium graminearum in Arabidopsis and barley, but it is unknown at which stage of the infection it acts. Since the rate of haustorial formation [...] Read more.
Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), induces disease resistance to the Fusarium head blight fungus Fusarium graminearum in Arabidopsis and barley, but it is unknown at which stage of the infection it acts. Since the rate of haustorial formation of an obligate biotrophic barley powdery mildew fungus Blumeria graminis f. sp. hordei (Bgh) was significantly reduced in NMN-treated coleoptile epidermal cells, the possibility that NMN induces resistance to the biotrophic stage of F. graminearum was investigated. The results show that NMN treatment caused the wandering of hyphal growth and suppressed the formation of appressoria-like structures. Furthermore, we developed an experimental system to monitor the early stage of infection in real-time and analyzed the infection behavior. We observed that the hyphae elongated windingly by NMN treatment. These results suggest that NMN potentiates resistance to the biotrophic invasion of F. graminearum as well as Bgh. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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15 pages, 1029 KiB  
Article
Efficiency of Hydroxycinnamic Phenolic Acids to Inhibit the Production of Ochratoxin A by Aspergillus westerdijkiae and Penicillium verrucosum
by Saranyaphat Boonmee, Vessela Atanasova, Sylvain Chéreau, Gisèle Marchegay, Kevin D. Hyde and Florence Richard-Forget
Int. J. Mol. Sci. 2020, 21(22), 8548; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228548 - 13 Nov 2020
Cited by 9 | Viewed by 2202
Abstract
Ochratoxin A (OTA) is one of the worldwide most important mycotoxins in terms of health and agroeconomic consequences. With the aim to promote the use of phytochemicals as alternatives to synthetic fungicides, the effect of hydroxycinnamic acids on the fungal growth and OTA [...] Read more.
Ochratoxin A (OTA) is one of the worldwide most important mycotoxins in terms of health and agroeconomic consequences. With the aim to promote the use of phytochemicals as alternatives to synthetic fungicides, the effect of hydroxycinnamic acids on the fungal growth and OTA yield by two major OTA-producing species was investigated. After a first step dedicated to the definition of most suitable culture conditions, the impact of 0.5 mM ferulic (FER), p-coumaric (COUM), caffeic and chlorogenic acids was evaluated on Aspergillus westerdijkiae and Penicillium verrucosum. Whereas no fungal growth reduction was observed regardless of the phenolic acid and fungal isolate, our results demonstrated the capacity of FER and COUM to inhibit OTA production. The most efficient compound was FER that led to a 70% reduction of OTA yielded by P. verrucosum and, although not statistically significant, a 35% inhibition of OTA produced by A. westerdijkiae. To further investigate the bioactivity of FER and COUM, their metabolic fate was characterized in fungal broths. The capacity of P. verrucosum to metabolize FER and COUM through a C2-clivage type degradation was demonstrated. Overall, our data support the potential use of FER to prevent OTA contamination and reduce the use of synthetic pesticides. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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17 pages, 2998 KiB  
Article
Aspergillus flavus Exploits Maize Kernels Using an “Orphan” Secondary Metabolite Cluster
by Ludovica Antiga, Sonia Roberta La Starza, Cecilia Miccoli, Simone D’Angeli, Valeria Scala, Marco Zaccaria, Xiaomei Shu, Gregory Obrian, Marzia Beccaccioli, Gary A. Payne and Massimo Reverberi
Int. J. Mol. Sci. 2020, 21(21), 8213; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218213 - 03 Nov 2020
Cited by 4 | Viewed by 2143
Abstract
Aspergillus flavus is a saprophytic cosmopolitan fungus, capable of infecting crops both pre- and post-harvest and exploiting different secondary metabolites, including aflatoxins. Aflatoxins are known carcinogens to animals and humans, but display no clear effect in host plants such as maize. In a [...] Read more.
Aspergillus flavus is a saprophytic cosmopolitan fungus, capable of infecting crops both pre- and post-harvest and exploiting different secondary metabolites, including aflatoxins. Aflatoxins are known carcinogens to animals and humans, but display no clear effect in host plants such as maize. In a previous study, we mined the genome of A. flavus to identify secondary metabolite clusters putatively involving the pathogenesis process in maize. We now focus on cluster 32, encoding for fungal effectors such as salicylate hydroxylase (SalOH), and necrosis- and ethylene-inducing proteins (npp1 domain protein) whose expression is triggered upon kernel contact. In order to understand the role of this genetic cluster in maize kernel infection, mutants of A. flavus, impaired or enhanced in specific functions (e.g., cluster 32 overexpression), were studied for their ability to cause disease. Within this frame, we conducted histological and histochemical experiments to verify the expression of specific genes within the cluster (e.g., SalOH, npp1), the production of salicylate, and the presence of its dehydroxylated form. Results suggest that the initial phase of fungal infection (2 days) of the living tissues of maize kernels (e.g., aleuron) coincides with a significant increase of fungal effectors such as SalOH and Npp1 that appear to be instrumental in eluding host defences and colonising the starch-enriched tissues, and therefore suggest a role of cluster 32 to the onset of infection. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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10 pages, 2030 KiB  
Communication
Heterologous Expression of the Core Genes in the Complex Fusarubin Gene Cluster of Fusarium Solani
by Tobias Bruun Pedersen, Mikkel Rank Nielsen, Sebastian Birkedal Kristensen, Eva Mie Lang Spedtsberg, Wafaa Yasmine, Rikke Matthiesen, Samba Evelyne Kabemba Kaniki, Trine Sørensen, Celine Petersen, Jens Muff, Teis Esben Sondergaard, Kåre Lehmann Nielsen, Reinhard Wimmer and Jens Laurids Sørensen
Int. J. Mol. Sci. 2020, 21(20), 7601; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207601 - 14 Oct 2020
Cited by 10 | Viewed by 2948
Abstract
Through stepwise recreation of the biosynthetic gene cluster containing PKS3 from Fusarium solani, it was possible to produce the core scaffold compound of bostrycoidin, a red aza-anthraquinone pigment in Saccharomyces cerevisiae. This was achieved through sequential transformation associated recombination (TAR) cloning [...] Read more.
Through stepwise recreation of the biosynthetic gene cluster containing PKS3 from Fusarium solani, it was possible to produce the core scaffold compound of bostrycoidin, a red aza-anthraquinone pigment in Saccharomyces cerevisiae. This was achieved through sequential transformation associated recombination (TAR) cloning of FvPPT, fsr1, fsr2, and fsr3 into the pESC-vector system, utilizing the inducible bidirectional galactose promoter for heterologous expression in S. cerevisiae. The production of the core metabolite bostrycoidin was investigated through triplicate growth cultures for 1–4 days, where the maximum titer of bostrycoidin was achieved after 2 days of induction, yielding 2.2 mg/L. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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32 pages, 2804 KiB  
Article
The brlA Gene Deletion Reveals That Patulin Biosynthesis Is Not Related to Conidiation in Penicillium expansum
by Chrystian Zetina-Serrano, Ophélie Rocher, Claire Naylies, Yannick Lippi, Isabelle P. Oswald, Sophie Lorber and Olivier Puel
Int. J. Mol. Sci. 2020, 21(18), 6660; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186660 - 11 Sep 2020
Cited by 9 | Viewed by 3387
Abstract
Dissemination and survival of ascomycetes is through asexual spores. The brlA gene encodes a C2H2-type zinc-finger transcription factor, which is essential for asexual development. Penicillium expansum causes blue mold disease and is the main source of patulin, a mycotoxin [...] Read more.
Dissemination and survival of ascomycetes is through asexual spores. The brlA gene encodes a C2H2-type zinc-finger transcription factor, which is essential for asexual development. Penicillium expansum causes blue mold disease and is the main source of patulin, a mycotoxin that contaminates apple-based food. A P. expansum PeΔbrlA deficient strain was generated by homologous recombination. In vivo, suppression of brlA completely blocked the development of conidiophores that takes place after the formation of coremia/synnemata, a required step for the perforation of the apple epicarp. Metabolome analysis displayed that patulin production was enhanced by brlA suppression, explaining a higher in vivo aggressiveness compared to the wild type (WT) strain. No patulin was detected in the synnemata, suggesting that patulin biosynthesis stopped when the fungus exited the apple. In vitro transcriptome analysis of PeΔbrlA unveiled an up-regulated biosynthetic gene cluster (PEXP_073960-PEXP_074060) that shares high similarity with the chaetoglobosin gene cluster of Chaetomium globosum. Metabolome analysis of PeΔbrlA confirmed these observations by unveiling a greater diversity of chaetoglobosin derivatives. We observed that chaetoglobosins A and C were found only in the synnemata, located outside of the apple, whereas other chaetoglobosins were detected in apple flesh, suggesting a spatial-temporal organization of the chaetoglobosin biosynthesis pathway. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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15 pages, 2747 KiB  
Article
Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
by Boyan Huang, Qingmei Chen, Lingling Wang, Xiaojuan Gao, Wenya Zhu, Peiqiang Mu and Yiqun Deng
Int. J. Mol. Sci. 2020, 21(18), 6517; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186517 - 06 Sep 2020
Cited by 54 | Viewed by 3512
Abstract
Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain [...] Read more.
Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB1 (300 μg/kg/day for 30 days). The toxicity of AFB1 on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB1 on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB1 concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB1 significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB1 induced apoptosis involving CASP3 and BAX. Taken together, AFB1 manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis—all of which are key factors for understanding the neurotoxicology of AFB1. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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23 pages, 3170 KiB  
Article
verA Gene is Involved in the Step to Make the Xanthone Structure of Demethylsterigmatocystin in Aflatoxin Biosynthesis
by Hongmei Zeng, Jingjing Cai, Hidemi Hatabayashi, Hiroyuki Nakagawa, Hiromitsu Nakajima and Kimiko Yabe
Int. J. Mol. Sci. 2020, 21(17), 6389; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176389 - 02 Sep 2020
Cited by 8 | Viewed by 2137
Abstract
In the biosynthesis of aflatoxin, verA, ver-1, ordB, and hypA genes of the aflatoxin gene cluster are involved in the pathway from versicolorin A (VA) to demethylsterigmatocystin (DMST). We herein isolated each disruptant of these four genes to determine their [...] Read more.
In the biosynthesis of aflatoxin, verA, ver-1, ordB, and hypA genes of the aflatoxin gene cluster are involved in the pathway from versicolorin A (VA) to demethylsterigmatocystin (DMST). We herein isolated each disruptant of these four genes to determine their functions in more detail. Disruptants of ver-1, ordB, and hypA genes commonly accumulated VA in their mycelia. In contrast, the verA gene disruptant accumulated a novel yellow fluorescent substance (which we named HAMA) in the mycelia as well as culture medium. Feeding HAMA to the other disruptants commonly caused the production of aflatoxins B1 (AFB1) and G1 (AFG1). These results indicate that HAMA pigment is a novel aflatoxin precursor which is involved at a certain step after those of ver-1, ordB, and hypA genes between VA and DMST. HAMA was found to be an unstable substance to easily convert to DMST and sterigmatin. A liquid chromatography-mass spectrometry (LC-MS) analysis showed that the molecular mass of HAMA was 374, and HAMA gave two close major peaks in the LC chromatogram in some LC conditions. We suggest that these peaks correspond to the two conformers of HAMA; one of them would be selectively bound on the substrate binding site of VerA enzyme and then converted to DMST. VerA enzyme may work as a key enzyme in the creation of the xanthone structure of DMST from HAMA. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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Review

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19 pages, 1843 KiB  
Review
Role of Tocochromanols in Tolerance of Cereals to Biotic Stresses: Specific Focus on Pathogenic and Toxigenic Fungal Species
by Jean-Marie Savignac, Vessela Atanasova, Sylvain Chéreau, Véronique Ortéga and Florence Richard-Forget
Int. J. Mol. Sci. 2022, 23(16), 9303; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169303 - 18 Aug 2022
Cited by 3 | Viewed by 1686
Abstract
Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this [...] Read more.
Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this goal requires a deep understanding of plant defense mechanisms, most of them involving specialized metabolites. However, while numerous studies have addressed the contribution of phenylpropanoids and carotenoids to plant chemical defense, very few have dealt with tocochromanols. Tocochromanols, which encompass tocopherols and tocotrienols and constitute the vitamin E family, are widely distributed in cereal kernels; their biosynthetic pathway has been extensively studied with the aim to enrich plant oils and combat vitamin E deficiency in humans. Here we provide strong assumptions arguing in favor of an involvement of tocochromanols in plant–fungal pathogen interactions. These assumptions are based on both direct effects resulting from their capacity to scavenge reactive oxygen species, including lipid peroxyl radicals, on their potential to inhibit fungal growth and mycotoxin yield, and on more indirect effects mainly based on their role in plant protection against abiotic stresses. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins 2.0)
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25 pages, 2117 KiB  
Review
Regulation of Secondary Metabolism in the Penicillium Genus
by Christelle El Hajj Assaf, Chrystian Zetina-Serrano, Nadia Tahtah, André El Khoury, Ali Atoui, Isabelle P. Oswald, Olivier Puel and Sophie Lorber
Int. J. Mol. Sci. 2020, 21(24), 9462; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249462 - 12 Dec 2020
Cited by 28 | Viewed by 6140
Abstract
Penicillium, one of the most common fungi occurring in a diverse range of habitats, has a worldwide distribution and a large economic impact on human health. Hundreds of the species belonging to this genus cause disastrous decay in food crops and are [...] Read more.
Penicillium, one of the most common fungi occurring in a diverse range of habitats, has a worldwide distribution and a large economic impact on human health. Hundreds of the species belonging to this genus cause disastrous decay in food crops and are able to produce a varied range of secondary metabolites, from which we can distinguish harmful mycotoxins. Some Penicillium species are considered to be important producers of patulin and ochratoxin A, two well-known mycotoxins. The production of these mycotoxins and other secondary metabolites is controlled and regulated by different mechanisms. The aim of this review is to highlight the different levels of regulation of secondary metabolites in the Penicillium genus. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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Review
Secondary Metabolites of the Rice Blast Fungus Pyricularia oryzae: Biosynthesis and Biological Function
by Takayuki Motoyama
Int. J. Mol. Sci. 2020, 21(22), 8698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228698 - 18 Nov 2020
Cited by 19 | Viewed by 3998
Abstract
Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Moreover, the relationship between pathogenicity and secondary metabolites remains unclear. To activate silent gene clusters in [...] Read more.
Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Moreover, the relationship between pathogenicity and secondary metabolites remains unclear. To activate silent gene clusters in fungi, successful approaches such as epigenetic control, promoter exchange, and heterologous expression have been reported. Pyricularia oryzae, a well-characterized plant pathogenic fungus, is the causal pathogen of rice blast disease. P. oryzae is also rich in secondary metabolism genes. However, biosynthetic genes for only four groups of secondary metabolites have been well characterized in this fungus. Biosynthetic genes for two of the four groups of secondary metabolites have been identified by activating secondary metabolism. This review focuses on the biosynthesis and roles of the four groups of secondary metabolites produced by P. oryzae. These secondary metabolites include melanin, a polyketide compound required for rice infection; pyriculols, phytotoxic polyketide compounds; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi including endophytes and plant pathogens; and tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique NRPS-PKS enzyme. Full article
(This article belongs to the Special Issue Molecular Biology and Chemistry of Mycotoxins and Phytotoxins)
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