PR Toxin – Biosynthesis, Genetic Regulation, Toxicological Potential, Prevention and Control Measures: Overview and Challenges

Dubey, Manish Kumar; Aamir, Mohd; Kaushik, Manish Singh; Khare, Saumya; Meena, Mukesh; Singh, Surendra; Upadhyay, Ram Sanmukh

doi:10.3389/fphar.2018.00288

Cited by 23 publications

(22 citation statements)

References 171 publications

(273 reference statements)

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“…Aristolochene is a sesquiterpene that is a precursor for mycotoxins such as the PR toxin produced by Penicillium roqueforti ( Jeleń, 2002 ; Dubey et al, 2018 ). Aristolochene was detected alongside the PR toxin and therefore it was proposed as a marker for the PR toxin ( Jeleń, 2002 ; Dubey et al, 2018 ). The biosynthetic cluster for the production of PR toxin and its precursors was recently characterized ( Hidalgo et al, 2014 , 2017 ).…”

Section: Resultsmentioning

confidence: 99%

“…It is biosynthesized from farnesyl pyrophosphate by aristolochene synthase (Proctor and Hohn, 1993). Aristolochene is a sesquiterpene that is a precursor for mycotoxins such as the PR toxin produced by Penicillium roqueforti (Jeleń, 2002;Dubey et al, 2018). Aristolochene was detected alongside the PR toxin and therefore it was proposed as a marker for the PR toxin (Jeleń, 2002;Dubey et al, 2018).…”

Section: Volatiles With a Strong Phylogenetic Signalmentioning

confidence: 99%

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Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

et al. 2020

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Microorganisms are diverse in their genome sequences and subsequently in their encoded metabolic pathways, which enabled them to adapt to numerous environmental conditions. They produce thousands of small molecules, many of which are volatiles in nature and play important roles in signaling in intra-and inter-species to kingdom and domain interactions, survival, or virulence. Many of these compounds have been studied, characterized, and organized in the mVOC 2.0 database. However, such dataset has not been investigated comprehensively in terms of its phylogeny to determine key volatile markers for certain taxa. It was hypothesized that some of the volatiles described in the mVOC 2.0 database could function as a phylogenetic signal since their production is conserved among certain taxa within the microbial evolutionary tree. Our meta-analysis revealed that some volatiles were produced by a large number of bacteria but not in fungal genera such as dimethyl disulfide, acetic acid, 2-nonanone, dimethyl trisulfide, 2-undecanone, isovaleric acid, 2-tridecanone, propanoic acid, and indole (common bacterial compounds). In contrast, 1-octen-3-ol, 3-octanone, and 2-pentylfuran (common fungal compounds) were produced primarily by fungal genera. Such chemical information was further confirmed by investigating genomic data of publicly available databases revealing that bacteria or fungi harbor gene families involved in these volatiles' biosynthesis. Our phylogenetic signal testing identified 61 volatiles with a significant phylogenetic signal as demonstrated by phylogenetic D statistic P-value < 0.05. Thirty-three volatiles were phylogenetically conserved in the bacterial domain (e.g., cyclocitral) compared to 17 volatiles phylogenetically conserved in the fungal kingdom (e.g., aristolochene), whereas 11 volatiles were phylogenetically conserved in genera from both bacteria and fungi (e.g., geosmin). These volatiles belong to different chemical classes such as heterocyclic compounds, long-chain fatty acids, sesquiterpenoids, and aromatics. The performed approaches serve as a starting point to investigate less explored volatiles with potential roles in signaling, antimicrobial therapy, or diagnostics.

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Section: Resultsmentioning

confidence: 99%

Section: Volatiles With a Strong Phylogenetic Signalmentioning

confidence: 99%

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

et al. 2020

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“…This cluster shows sequence similarity to three proteins within the PR toxin biosynthetic gene cluster, namely aristolochene synthase (accession CDM31315.1) with 60% similarity to D9617_1g083910, short-chain dehydrogenase/reductase (accession CDM31317.1) with 54% similarity D9617_1g083830 and the type 2 FAD-binding protein (accession CDM31316.1) with 42% similarity to D9617_1g083960. The PR toxin is produced by the saprobe Penicillium roqueforti , a known contaminant of silages [155], while the mechanisms of its likely role in plant degeneration are unknown [156], PR toxin is seen to induce necrosis in human intestinal epithelial cells and monocytic immune cells [157] and exhibits mutagenic activity towards rats [158]. Thus, indicating the potential production of a toxin by E. fawcettii with DNA-binding capabilities.…”

Section: Resultsmentioning

confidence: 99%

Genome mining of the citrus pathogenElsinoë fawcettii; prediction and prioritisation of candidate effectors, cell wall degrading enzymes and secondary metabolite gene clusters

Jeffress

Arun‐Chinnappa

Stodart

et al. 2019

Preprint

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Abstract:Elsinoë fawcettii, a necrotrophic fungal pathogen, causes citrus scab on numerous citrus varieties around the world. Known pathotypes of E. fawcettii are based on host range; additionally, cryptic pathotypes have been reported and more novel pathotypes are thought to exist. E. fawcettii produces elsinochrome, a non-host selective toxin which contributes to virulence. However, the mechanisms involved in potential pathogen-host interactions occurring prior to the production of elsinochrome are unknown, yet the host-specificity observed among pathotypes suggests a reliance upon such mechanisms. In this study we have generated a whole genome sequencing project for E. fawcettii, producing an annotated draft assembly 26.01 Mb in size, with 10,080 predicted gene models and low (0.37%) coverage of transposable elements. The assembly showed evidence of AT-rich regions, potentially indicating genomic regions with increased plasticity. Using a variety of computational tools, we mined the E. fawcettii genome for potential virulence genes as candidates for future investigation. A total of 1,280 secreted proteins and 203 candidate effectors were predicted and compared to those of other necrotrophic (Botrytis cinerea, Parastagonospora nodorum, Pyrenophora tritici-repentis, Sclerotinia sclerotiorum and Zymoseptoria tritici), hemibiotrophic (Leptosphaeria maculans, Magnaporthe oryzae, Rhynchosporium commune and Verticillium dahliae) and biotrophic (Ustilago maydis) plant pathogens. Genomic and proteomic features of known fungal effectors were analysed and used to guide the prioritisation of 77 candidate effectors of E. fawcettii. Additionally, 378 carbohydrate-active enzymes were predicted and analysed for likely secretion and sequence similarity with known virulence genes. Furthermore, secondary metabolite prediction indicated nine additional genes potentially involved in the elsinochrome biosynthesis gene cluster than previously described. A further 21 secondary metabolite clusters were predicted, some with similarity to known toxin producing gene clusters. The candidate virulence genes predicted in this study provide a comprehensive resource for future experimental investigation into the pathogenesis of E. fawcettii.

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“…The bicyclic sesquiterpene PR-toxin can cause significant damage to liver and kidney, induce abortions and reduce fertility in cattle. However, its derivatives such as PR-acid and PR-imine are largely non-toxic and unstable [ 53 ]. The biosynthesis of PR-toxin requires at least four genes, i.e., Prx1-Prx4 in P. roqueforti [ 54 ].…”

Section: Unknown Mycotoxins May Be Produced By Cordycepsmentioning

confidence: 99%

Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

Chen

Sun

Luo

et al. 2020

Toxins

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Ascomycete Cordyceps fungi such as C. militaris, C. cicadae, and C. guangdongensis have been mass produced on artificial media either as food supplements or health additives while the byproducts of culture substrates are largely used as animal feed. The safety concerns associated with the daily consumption of Cordyceps fungi or related products are still being debated. On the one hand, the known compounds from these fungi such as adenosine analogs cordycepin and pentostatin have demonstrated different beneficial or pharmaceutical activities but also dose-dependent cytotoxicities, neurological toxicities and or toxicological effects in humans and animals. On the other hand, the possibility of mycotoxin production by Cordyceps fungi has not been completely ruled out. In contrast to a few metabolites identified, an array of biosynthetic gene clusters (BGCs) are encoded in each genome of these fungi with the potential to produce a plethora of as yet unknown secondary metabolites. Conservation analysis of BGCs suggests that mycotoxin analogs of PR-toxin and trichothecenes might be produced by Cordyceps fungi. Future elucidation of the compounds produced by these functionally unknown BGCs, and in-depth assessments of metabolite bioactivity and chemical safety, will not only facilitate the safe use of Cordyceps fungi as human food or alternative medicine, but will also benefit the use of mass production byproducts as animal feed. To corroborate the long record of use as a traditional medicine, future efforts will also benefit the exploration of Cordyceps fungi for pharmaceutical purposes.

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PR Toxin – Biosynthesis, Genetic Regulation, Toxicological Potential, Prevention and Control Measures: Overview and Challenges

Cited by 23 publications

References 171 publications

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

Sixty-One Volatiles Have Phylogenetic Signals Across Bacterial Domain and Fungal Kingdom

Genome mining of the citrus pathogenElsinoë fawcettii; prediction and prioritisation of candidate effectors, cell wall degrading enzymes and secondary metabolite gene clusters

Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

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