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Daniel G. Panaccione - One of the best experts on this subject based on the ideXlab platform.
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Short title: Aspergillus fumigatus Ergot alkaloid diversity Chemotypic and genotypic diversity in the Ergot alkaloid pathway of Aspergillus fumigatus
2020Co-Authors: Sarah L. Robinson, Daniel G. PanaccioneAbstract:Aspergillus fumigatus is an opportunistic human pathogen that synthesizes a group of mycotoxins via a branch of the Ergot alkaloid pathway. This fungus is globally distributed, and genetic data indicate that isolates recombine freely over that range; however, previous work on Ergot alkaloids has focused on a limited number of isolates. We hypothesized that A. fumigatus harbors variation in the chemotype of Ergot alkaloids and genotype of the Ergot alkaloid gene cluster. Analysis of 13 isolates by high performance liquid chromatography revealed four distinct Ergot alkaloid profiles or chemotypes. Five isolates completed the A. fumigatus branch of the Ergot alkaloid pathway to fumigaclavine C. Six independent isolates accumulated fumigaclavine A, the pathway intermediate immediately before fumigaclavine C. One isolate accumulated only the early pathway intermediates chanoclavine-I and chanoclavine-I aldehyde, and one isolate lacked Ergot alkaloids altogether. A genetic basis for each of the observed chemotypes was obtained either by PCR analysis of the Ergot alkaloid gene cluster or through sequencing of easL, the gene encoding the prenyl transferase that reverse prenylates fumigaclavine A to fumigaclavine C. Isolates also exhibited differences in pigmentation and sporulation. The Ergot alkaloid chemotypes were widely distributed geographically and among substrate of origin.
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Ergot Alkaloid Synthesis Capacity of Penicillium camemberti.
Applied and Environmental Microbiology, 2018Co-Authors: Samantha J. Fabian, Matthew D. Maust, Daniel G. PanaccioneAbstract:ABSTRACT Ergot alkaloids are specialized fungal metabolites with potent biological activities. They are encoded by well-characterized gene clusters in the genomes of producing fungi. Penicillium camemberti plays a major role in the ripening of Brie and Camembert cheeses. The P. camemberti genome contains a cluster of five genes shown in other fungi to be required for synthesis of the important Ergot alkaloid intermediate chanoclavine-I aldehyde and two additional genes (easH and easQ) that may control modification of chanoclavine-I aldehyde into other Ergot alkaloids. We analyzed samples of Brie and Camembert cheeses, as well as cultures of P. camemberti, and did not detect chanoclavine-I aldehyde or its derivatives. To create a functioning facsimile of the P. camembertieas cluster, we expressed P. camemberti easH and easQ in a chanoclavine-I aldehyde-accumulating easA knockout mutant of Neosartorya fumigata. The easH-easQ-engineered N. fumigata strain accumulated a pair of compounds of m/z 269.1288 in positive-mode liquid chromatography-mass spectrometry (LC-MS). The analytes fragmented in a manner typical of the stereoisomeric Ergot alkaloids rugulovasine A and B, and the related rugulovasine producer Penicillium biforme accumulated the same isomeric pair of analytes. The P. camemberti eas genes were transcribed in culture, but comparison of the P. camemberti eas cluster with the functional cluster from P. biforme indicated 11 polymorphisms. Whereas other P. camembertieas genes functioned when expressed in N. fumigata, P. camembertieasC did not restore Ergot alkaloids when expressed in an easC mutant. The data indicate that P. camemberti formerly had the capacity to produce the Ergot alkaloids rugulovasine A and B. IMPORTANCE The presence of Ergot alkaloid synthesis genes in the genome of Penicillium camemberti is significant, because the fungus is widely consumed in Brie and Camembert cheeses. Our results show that, although the fungus has several functional genes from the Ergot alkaloid pathway, it produces only an early pathway intermediate in culture and does not produce Ergot alkaloids in cheese. Penicillium biforme, a close relative of P. camemberti, contains a similar but fully functional set of Ergot alkaloid synthesis genes and produces Ergot alkaloids chanoclavine-I, chanoclavine-I aldehyde, and rugulovasine A and B. Our reconstruction of the P. camemberti pathway in the model fungus Neosartorya fumigata indicated that P. camemberti formerly had the capacity to produce these same Ergot alkaloids. Neither P. camemberti nor P. biforme produced Ergot alkaloids in cheese, indicating that nutritionally driven gene regulation prevents these fungi from producing Ergot alkaloids in a dairy environment.
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Ergot alkaloids of the family clavicipitaceae
Phytopathology, 2017Co-Authors: Simona Florea, Daniel G. Panaccione, Christopher L SchardlAbstract:Ergot alkaloids are highly diverse in structure, exhibit diverse effects on animals, and are produced by diverse fungi in the phylum Ascomycota, including pathogens and mutualistic symbionts of plants. These mycotoxins are best known from the fungal family Clavicipitaceae and are named for the Ergot fungi that, through millennia, have contaminated grains and caused mass poisonings, with effects ranging from dry gangrene to convulsions and death. However, they are also useful sources of pharmaceuticals for a variety of medical purposes. More than a half-century of research has brought us extensive knowledge of Ergot-alkaloid biosynthetic pathways from common early steps to several taxon-specific branches. Furthermore, a recent flurry of genome sequencing has revealed the genomic processes underlying Ergot-alkaloid diversification. In this review, we discuss the evolution of Ergot-alkaloid biosynthesis genes and gene clusters, including roles of gene recruitment, duplication and neofunctionalization, as wel...
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identification and structural elucidation of Ergotryptamine a new Ergot alkaloid produced by genetically modified aspergillus nidulans and natural isolates of epichloe species
Journal of Agricultural and Food Chemistry, 2015Co-Authors: Katy L Ryan, Novruz G Akhmedov, Daniel G. PanaccioneAbstract:Ergot alkaloid pathway reconstruction in Aspergillus nidulans is an approach used to better understand the biosynthesis of these mycotoxins. An engineered strain named A. nidulans WFC (expressing Ergot alkaloid synthesis genes dmaW, easF, and easC) produced the established intermediate N-methyl-4-dimethylallyltryptophan, as well as an uncharacterized Ergot alkaloid. We investigated the chemical structure of the new metabolite and its role in the Ergot alkaloid pathway. Mass spectrometry, labeling, and NMR studies showed that the unknown Ergot alkaloid, designated here as Ergotryptamine, differed from N-methyl-4-dimethylallyltryptophan by the loss of the carboxyl group, addition of a hydroxyl group, and shift in position of a carbon–carbon double bond. Feeding studies with Aspergillus mutants did not show Ergotryptamine turnover, suggesting it is a pathway byproduct as opposed to an authentic intermediate. Several Epichloe species also produced this metabolite, and further investigations revealed the equiv...
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partial reconstruction of the Ergot alkaloid pathway by heterologous gene expression in aspergillus nidulans
Toxins, 2013Co-Authors: Katy L Ryan, Christopher T Moore, Daniel G. PanaccioneAbstract:Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among Ergot alkaloid producers. At least four genes, dmaW, easF, easE, and easC, are necessary for pathway steps prior to chanoclavine-I; however, the sufficiency of these genes for chanoclavine-I synthesis has not been established. A fragment of genomic DNA containing dmaW, easF, easE, and easC was amplified from the human-pathogenic, Ergot alkaloid-producing fungus Aspergillus fumigatus and transformed into Aspergillus nidulans, a model fungus that does not contain any of the Ergot alkaloid synthesis genes. HPLC and LC-MS analyses demonstrated that transformed A. nidulans strains produced chanoclavine-I and an earlier pathway intermediate. Aspergillus nidulans transformants containing dmaW, easF, and either easE or easC did not produce chanoclavine-I but did produce an early pathway intermediate and, in the case of the easC transformant, an additional Ergot alkaloid-like compound. We conclude that dmaW, easF, easE, and easC are sufficient for the synthesis of chanoclavine-I in A. nidulans and expressing Ergot alkaloid pathway genes in A. nidulans provides a novel approach to understanding the early steps in Ergot alkaloid synthesis.
Hans-ulrich Humpf - One of the best experts on this subject based on the ideXlab platform.
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Identification and characterization of the ergochrome gene cluster in the plant pathogenic fungus Claviceps purpurea
Fungal Biology and Biotechnology, 2016Co-Authors: Lisa Neubauer, Fj Bove, Bi Shaw, P Mantle, Julian Dopstadt, Paul Tudzynski, Hans-ulrich Humpf, E LuttrellAbstract:Claviceps purpurea is a phytopathogenic fungus infecting a broad range of grasses including economically important cereal crop plants. The infection cycle ends with the formation of the typical purple-black pigmented sclerotia containing the toxic Ergot alkaloids. Besides these Ergot alkaloids little is known about the secondary metabolism of the fungus. Red anthraquinone derivatives and yellow xanthone dimers (ergochromes) have been isolated from sclerotia and described as Ergot pigments, but the corresponding gene cluster has remained unknown. Fungal pigments gain increasing interest for example as environmentally friendly alternatives to existing dyes. Furthermore, several pigments show biological activities and may have some pharmaceutical value. This study identified the gene cluster responsible for the synthesis of the Ergot pigments. Overexpression of the cluster-specific transcription factor led to activation of the gene cluster and to the production of several known Ergot pigments. Knock out of the cluster key enzyme, a nonreducing polyketide synthase, clearly showed that this cluster is responsible for the production of red anthraquinones as well as yellow ergochromes. Furthermore, a tentative biosynthetic pathway for the Ergot pigments is proposed. By changing the culture conditions, pigment production was activated in axenic culture so that high concentration of phosphate and low concentration of sucrose induced pigment syntheses. This is the first functional analysis of a secondary metabolite gene cluster in the Ergot fungus besides that for the classical Ergot alkaloids. We demonstrated that this gene cluster is responsible for the typical purple-black color of the Ergot sclerotia and showed that the red and yellow Ergot pigments are products of the same biosynthetic pathway. Activation of the gene cluster in axenic culture opened up new possibilities for biotechnological applications like the dye production or the development of new pharmaceuticals.
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permeability of Ergot alkaloids across the blood brain barrier in vitro and influence on the barrier integrity
Molecular Nutrition & Food Research, 2012Co-Authors: Dennis Mulac, Sabine Huwel, Hansjoachim Galla, Hans-ulrich HumpfAbstract:Scope Ergot alkaloids are secondary metabolites of Claviceps spp. and they have been in the focus of research for many years. Experiments focusing on Ergotamine as a former migraine drug referring to the ability to reach the brain revealed controversial results. The question to which extent Ergot alkaloids are able to cross the blood-brain barrier is still not answered. Methods and results In order to answer this question we have studied the ability of Ergot alkaloids to penetrate the blood-brain barrier in a well established in vitro model system using primary porcine brain endothelial cells. It could clearly be demonstrated that Ergot alkaloids are able to cross the blood-brain barrier in high quantities in only a few hours. We could further identify an active transport for ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations concerning barrier integrity properties have identified ergocristinine as a potent substance to accumulate in these cells ultimately leading to a weakened barrier function. Conclusion For the first time we could show that the so far as biologically inactive described 8-(S) isomers of Ergot alkaloids seem to have an influence on barrier integrity underlining the necessity for a risk assessment of Ergot alkaloids in food and feed.
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Cytotoxicity and accumulation of Ergot alkaloids in human primary cells
Toxicology, 2011Co-Authors: Dennis Mulac, Hans-ulrich HumpfAbstract:Abstract Ergot alkaloids are secondary metabolites produced by fungi of the species Claviceps . Toxic effects after consumption of contaminated grains are described since mediaeval times. Of the more than 40 known Ergot alkaloids six are found predominantly. These are Ergotamine, ergocornine, ergocryptine, ergocristine, ergosine and ergometrine, along with their corresponding isomeric forms (-inine-forms). Toxic effects are known to be induced by an interaction of the Ergot alkaloids as neurotransmitters, like dopamine or serotonin. Nevertheless data concerning cytotoxic effects are missing and therefore a screening of the six main Ergot alkaloids was performed in human primary cells in order to evaluate the toxic potential. As it is well known that Ergot alkaloids isomerize easily the stability was tested in the cell medium. Based on these results factors were calculated to correct the used concentration values to the biologically active lysergic (-ine) form. These factors range from 1.4 for the most stable compound ergometrine to 5.0 for the most unstable Ergot alkaloid ergocristine. With these factors, reflecting the instability, several controverse literature data concerning the toxicity could be explained. To evaluate the cytotoxic effects of Ergot alkaloids, human cells in primary culture were used. These cells remain unchanged in contrast to cell lines and the data allow a better comparison to the in vivo situation than using immortalized cell lines. To characterize the effects on primary cells, renal proximal tubule epithelial cells (RPTEC) and normal human astrocytes (NHA) were used. The parameters necrosis (LDH-release) and apoptosis (caspase-3-activation, DNA condensation and fragmentation) were distinguished. The results show that depending on the individual structure of the peptide Ergot alkaloids the toxic properties change. While ergometrine as a lysergic acid amide did not show any effect, the peptide Ergot alkaloids revealed a different toxic potential. Of all tested Ergot alkaloids ergocristine was the most cytotoxic compound inducing apoptosis in human kidney cells starting at a concentration of 1 μM in RPTEC. Uptake studies underline the cytotoxic properties, with an accumulation of peptide Ergot alkaloids and no uptake of ergometrine. The results represent a new description of effects of Ergot alkaloids regarding cytotoxicity and accumulation in human primary cells. For the first time apoptosis has been identified besides well described receptor effects. This gives a hint for a more complex mode of action of Ergot alkaloids than described in literature so far.
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Distribution of Ergot alkaloids and ricinoleic acid in different milling fractions
Mycotoxin Research, 2011Co-Authors: Carolin Franzmann, Jan Schröder, Klaus Mϋnzing, Klaus Wolf, Meinolf G. Lindhauer, Hans-ulrich HumpfAbstract:The sclerotia of the fungus Claviceps sp. are still a challenge for the milling industry. Ergot sclerotia are a constant contamination of the rye crop and have to be removed by modern milling technologies. Changing sizes and coloration of the sclerotia make it difficult to separate them from the grain. Ergot sclerotia are a problem when cleaning is insufficient and non-separated specimens or sclerotia fragments get into the milling stream and thus Ergot alkaloids are distributed into the different cereal fractions. In model milling experiments, the residues of Ergot in rye flour and the distribution of Ergot into different milling fractions were investigated. Rye grains were mixed with whole Ergot sclerotia and in another experiment with Ergot powder and cleaned afterwards before milling. The Ergot alkaloids ergometrine, ergosine, Ergotamine, ergocornine, ergocryptine, ergocristineand their related isomeric forms (-inine-forms), and additionally ricinoleic acid as a characteristic component of Ergot, were quantified in the different milling fractions. From the first experiment, it can be shown that after harvesting even simple contact of sclerotia with bulk grains during ordinary handling or movement of bulk grain in the granary is sufficient to contaminate all the healthy or sound rye grains with Ergot alkaloids. Thereby, the amount of Ergot residue correlates with the amount of peripheral layers of rye grains in the flour. In an additional experiment without sclerotia specimens, bulk rye grains were loaded with powder of sclerotia. After subsequent cleaning, aconcentration of Ergot alkaloids was detected, which was tenfold higher than the Ergot alkaloidconcentration of the experiment with intact Ergot sclerotia.
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Ricinoleic Acid as a Marker for Ergot Impurities in Rye and Rye Products
Journal of Agricultural and Food Chemistry, 2010Co-Authors: Carolin Franzmann, Johannes Wächter, Natascha Dittmer, Hans-ulrich HumpfAbstract:Ergot alkaloid and ricinoleic acid contents of 63 Ergot sclerotia samples from rye throughout Germany of the harvest years 2006−2009 were determined. Alkaloid contents were analyzed by means of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) and ricinoleic acid contents by means of gas chromatography with flame ionization detection (GC-FID). Ergot alkaloid amounts ranged from 0.01 to 0.2 g/100 g of sclerotia with an average amount of 0.08 g/100 g. Ergotamine and ergocristine were identified as lead alkaloids representing 57% (w/w) of the total alkaloid content. The average ricinoleic acid amount in the Ergot sclerotia was 10.3 g/100 g. Because of the low variation of ricinoleic acid content in the Ergot sclerotia, a new method for the determination of ricinoleic acid in rye products as a marker for Ergot contaminations was developed. This method allows the determination of Ergot impurities as low as 0.01% (w/w). Furthermore, 29 rye products (flours, bread mix, bread) were inv...
Stewart J. Tepper - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the Role of Ergots in the Treatment of Migraine
2020Co-Authors: Eric P. Baron, Stewart J. TepperAbstract:The harmful side effects of the Ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of Ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans.Triptans are very efficacious for many migraineurs,and since their widespread use, use of Ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans,yet respond very well to Ergots.Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans.This lack of receptor specificity explains potential Ergot side effects, but may also account for efficacy. The role of Ergots in headache should be revisited, especially in view of newer Ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroErgotamine. Redefining where in the headache treatment spectrum Ergots belong and deciding when they may be the optimal choice of treatment is necessary.
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Revisiting the role of Ergots in the treatment of migraine and headache.
Headache, 2010Co-Authors: Eric P. Baron, Stewart J. TepperAbstract:(Headache 2010;50:1353-1361) The harmful side effects of the Ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of Ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of Ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to Ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential Ergot side effects, but may also account for efficacy. The role of Ergots in headache should be revisited, especially in view of newer Ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroErgotamine. Redefining where in the headache treatment spectrum Ergots belong and deciding when they may be the optimal choice of treatment is necessary.
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Ergotamine and dihydroErgotamine a review
Current Pain and Headache Reports, 2003Co-Authors: Marcelo E Bigal, Stewart J. TepperAbstract:The Ergot alkaloids were the first specific antimigraine therapy available. However, with the advent of the triptans, their use in the treatment of migraine has declined and their role has become less clear. This review discusses the pharmacology, efficacy, and safety of the Ergots. In randomized clinical trials, oral Ergotamine was found to be superior to placebo, but inferior to 100 mg of oral sumatriptan. In contrast, rectal Ergotamine was found to have higher efficacy (73% headache relief) than rectal sumatriptan (63% headache relief). Intranasal dihydroErgotamine was found to be superior to placebo, but less effective than subcutaneous and intranasal sumatriptan. Ergotamine is still widely used in some countries for the treatment of severe migraine attacks. It is generally regarded as a safe and useful drug if prescribed for infrequent use, in the correct dose, and in the absence of contraindications; however, safer and more effective options do exist in the triptans. In patients with status migrainous and patients with frequent headache recurrence, Ergotamine is still probably useful.
Carolin Franzmann - One of the best experts on this subject based on the ideXlab platform.
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Distribution of Ergot alkaloids and ricinoleic acid in different milling fractions
Mycotoxin Research, 2011Co-Authors: Carolin Franzmann, Jan Schröder, Klaus Mϋnzing, Klaus Wolf, Meinolf G. Lindhauer, Hans-ulrich HumpfAbstract:The sclerotia of the fungus Claviceps sp. are still a challenge for the milling industry. Ergot sclerotia are a constant contamination of the rye crop and have to be removed by modern milling technologies. Changing sizes and coloration of the sclerotia make it difficult to separate them from the grain. Ergot sclerotia are a problem when cleaning is insufficient and non-separated specimens or sclerotia fragments get into the milling stream and thus Ergot alkaloids are distributed into the different cereal fractions. In model milling experiments, the residues of Ergot in rye flour and the distribution of Ergot into different milling fractions were investigated. Rye grains were mixed with whole Ergot sclerotia and in another experiment with Ergot powder and cleaned afterwards before milling. The Ergot alkaloids ergometrine, ergosine, Ergotamine, ergocornine, ergocryptine, ergocristineand their related isomeric forms (-inine-forms), and additionally ricinoleic acid as a characteristic component of Ergot, were quantified in the different milling fractions. From the first experiment, it can be shown that after harvesting even simple contact of sclerotia with bulk grains during ordinary handling or movement of bulk grain in the granary is sufficient to contaminate all the healthy or sound rye grains with Ergot alkaloids. Thereby, the amount of Ergot residue correlates with the amount of peripheral layers of rye grains in the flour. In an additional experiment without sclerotia specimens, bulk rye grains were loaded with powder of sclerotia. After subsequent cleaning, aconcentration of Ergot alkaloids was detected, which was tenfold higher than the Ergot alkaloidconcentration of the experiment with intact Ergot sclerotia.
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Ricinoleic Acid as a Marker for Ergot Impurities in Rye and Rye Products
Journal of Agricultural and Food Chemistry, 2010Co-Authors: Carolin Franzmann, Johannes Wächter, Natascha Dittmer, Hans-ulrich HumpfAbstract:Ergot alkaloid and ricinoleic acid contents of 63 Ergot sclerotia samples from rye throughout Germany of the harvest years 2006−2009 were determined. Alkaloid contents were analyzed by means of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) and ricinoleic acid contents by means of gas chromatography with flame ionization detection (GC-FID). Ergot alkaloid amounts ranged from 0.01 to 0.2 g/100 g of sclerotia with an average amount of 0.08 g/100 g. Ergotamine and ergocristine were identified as lead alkaloids representing 57% (w/w) of the total alkaloid content. The average ricinoleic acid amount in the Ergot sclerotia was 10.3 g/100 g. Because of the low variation of ricinoleic acid content in the Ergot sclerotia, a new method for the determination of ricinoleic acid in rye products as a marker for Ergot contaminations was developed. This method allows the determination of Ergot impurities as low as 0.01% (w/w). Furthermore, 29 rye products (flours, bread mix, bread) were inv...
Christopher L Schardl - One of the best experts on this subject based on the ideXlab platform.
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Ergot alkaloids of the family clavicipitaceae
Phytopathology, 2017Co-Authors: Simona Florea, Daniel G. Panaccione, Christopher L SchardlAbstract:Ergot alkaloids are highly diverse in structure, exhibit diverse effects on animals, and are produced by diverse fungi in the phylum Ascomycota, including pathogens and mutualistic symbionts of plants. These mycotoxins are best known from the fungal family Clavicipitaceae and are named for the Ergot fungi that, through millennia, have contaminated grains and caused mass poisonings, with effects ranging from dry gangrene to convulsions and death. However, they are also useful sources of pharmaceuticals for a variety of medical purposes. More than a half-century of research has brought us extensive knowledge of Ergot-alkaloid biosynthetic pathways from common early steps to several taxon-specific branches. Furthermore, a recent flurry of genome sequencing has revealed the genomic processes underlying Ergot-alkaloid diversification. In this review, we discuss the evolution of Ergot-alkaloid biosynthesis genes and gene clusters, including roles of gene recruitment, duplication and neofunctionalization, as wel...
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Introduction to the Toxins Special Issue on Ergot Alkaloids
Toxins, 2015Co-Authors: Christopher L SchardlAbstract:Ergot alkaloids are among the most relevant natural products in the history of toxins and pharmaceuticals. Until the late 20th century, human and livestock exposure to Ergot alkaloids was primarily through ingestion of “Ergots,” which are spur-shaped or seed-like resting structures (sclerotia) of Ergot fungi, the Claviceps species. Because Ergots have similar density to grains, traditional threshing techniques generally failed to remove them, and outbreaks of Ergot typically led to mass poisonings. [...]
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Contribution of Ergot alkaloids to suppression of a grass‐feeding caterpillar assessed with gene knockout endophytes in perennial ryegrass
Entomologia Experimentalis Et Applicata, 2008Co-Authors: Daniel A. Potter, J. Tyler Stokes, Carl T. Redmond, Christopher L Schardl, Daniel G. PanaccioneAbstract:Neotyphodium and Epichloe species (Ascomycota: Clavicipitaceae) are fungal symbionts (endophytes) of grasses. Many of these endophytes produce alkaloids that enhance their hosts' resistance to insects or are toxic to grazing mammals. The goals of eliminating from forage grasses factors such as Ergot alkaloids that are responsible for livestock disorders, while retaining pasture sustainability, and of developing resistant turf grasses, require better understanding of how particular alkaloids affect insect herbivores. We used perennial ryegrass Lolium perenne L. (Poaceae) symbiotic with Neotyphodium lolii x Epichloe typhina isolate Lp1 (a natural interspecific hybrid), as well as with genetically modified strains of Lp1 with altered Ergot alkaloid profiles, to test effects of Ergot alkaloids on feeding, growth, and survival of the black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), a generalist grass-feeding caterpillar. Neonates or late instars were provided clippings from glasshouse-grown plants in choice and rearing trials. Wild-type endophytic grass showed strong antixenosis and antibiosis, especially to neonates. Plant-endophyte symbiota from which complex Ergot alkaloids (ergovaline and lysergic acid amides such as ergine) or all Ergot alkaloids were eliminated by endophyte gene knockout retained significant resistance against neonates. However, this activity was reduced compared to that of wild-type Lp1, providing the first direct genetic evidence that Ergot alkaloids contribute to insect resistance of endophytic grasses. Similarity of larval response to the two mutants suggested that ergovaline and/or ergine account for the somewhat greater potency of wild-type Lp1 compared to the knockouts, whereas simpler Ergot alkaloids contribute little to that added resistance. All of the endophyte strains also produced peramine, which was probably their primary resistance component. This study suggests that Ergot alkaloids can be eliminated from an endophyte of perennial ryegrass while retaining significant insect resistance.
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effects of Ergot alkaloids on food preference and satiety in rabbits as assessed with gene knockout endophytes in perennial ryegrass lolium perenne
Journal of Agricultural and Food Chemistry, 2006Co-Authors: Daniel G. Panaccione, Caroline Machado, Christopher L Schardl, Jessica R Cipoletti, Andrea B Sedlock, Kenneth P Blemings, George E SeidelAbstract:Neotyphodium species are fungal endophytes best known for their protection of grass hosts and production of bioactive metabolites including Ergot alkaloids. Perennial ryegrass−Neotyphodium sp. Lp1 symbiota that have altered Ergot alkaloid profiles (resulting from knockouts in two different endophyte genes) were fed, along with controls, to rabbits to test the effects of Ergot alkaloids on food preference and satiety. Interestingly, rabbits dramatically preferred plants that were endophyte-infected but free of Ergot alkaloids over endophyte-free plants (P = 0.01). Accumulation of Ergot alkaloids of the clavine class counteracted the added appeal of endophyte-infected plants. In satiety tests, consumption of ergovaline (the ultimate Ergot pathway product in wild-type endophyte), but not of several other Ergot alkaloids, during an initial meal had a negative effect on subsequent rabbit chow consumption (P < 0.05). The data indicate that clavines were sufficient to reduce the appeal of endophyte-infected gras...
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Loline and Ergot Alkaloids in Grass Endophytes
2006Co-Authors: Christopher L Schardl, Jimmy D. Blankenship, Martin J. Spiering, Caroline MachadoAbstract:Many of the common grasses in woodlands and meadows, pastures, lawns, roadsides, and sport fields are aided in their survival by inconspicuous fungal symbionts, termed endophytes. The Epichloe spp. and Neotyphodium spp. (asexual counterparts of Epichloe spp.) are grass endophytes belonging to the fungal family Clavicipitaceae (phylum Ascomycota, order Hypocreales). The family Clavicipitaceae is best known for the Ergot fungi, Claviceps spp., which do not engage in such benign symbioses as do their endophytic cousins. Instead, Claviceps spp. infect florets on developing seed heads, where they replace ovaries with hard, dormant sclerotia. These ‘‘Ergots’’ often contain high levels of alkaloids with neurotropic activities in vertebrates and insects. The term Ergot alkaloids (also known as ergoline alkaloids, ergoalkaloids, or Ergotoxins) refers to one class of such metabolites, especially those from Claviceps purpurea. Sclerotia of C. purpurea contain approx. 1% (dry mass) of the ergopeptines, Ergotamine, and ergocristine [1]. In addition to the Ergot alkaloid class, however, some Claviceps spp. also produce indole-diterpene tremorgens that are built from similar precursors but are structurally and pharmacologically quite different from Ergot alkaloids. The tremorgens, which are also neurotropic and active against vertebrates
