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Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci.

Schardl CL, Young CA, Hesse U, Amyotte SG, Andreeva K, Calie PJ, Fleetwood DJ, Haws DC, Moore N, Oeser B, Panaccione DG, Schweri KK, Voisey CR, Farman ML, Jaromczyk JW, Roe BA, O'Sullivan DM, Scott B, Tudzynski P, An Z, Arnaoudova EG, Bullock CT, Charlton ND, Chen L, Cox M, Dinkins RD, Florea S, Glenn AE, Gordon A, Güldener U, Harris DR, Hollin W, Jaromczyk J, Johnson RD, Khan AK, Leistner E, Leuchtmann A, Li C, Liu J, Liu J, Liu M, Mace W, Machado C, Nagabhyru P, Pan J, Schmid J, Sugawara K, Steiner U, Takach JE, Tanaka E, Webb JS, Wilson EV, Wiseman JL, Yoshida R, Zeng Z - PLoS Genet. (2013)

Bottom Line: Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals.We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids.We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, USA. Schardl@uky.edu

ABSTRACT
The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.

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Ergot alkaloids and summary of biosynthesis pathway.(A) Ergoline alkaloid biosynthesis pathways in the Clavicipitaceae. Arrows indicate one or more steps catalyzed by products of genes indicated. Arrows and genes in blue indicate steps in synthesis of the first fully cyclized intermediate (skeleton). Variation in the easA gene (underlined) determines whether the ergoline skeleton is festuclavine or agroclavine. Arrows and genes in red indicate steps in decoration of the skeleton to give the variety of ergolines in the Clavicipitaceae. Asterisks indicate genes newly discovered in the genome sequences of C. paspali, N. gansuense var. inebrians and P. ipomoeae. (B) Ergopeptines produced by strains in this study.
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pgen-1003323-g002: Ergot alkaloids and summary of biosynthesis pathway.(A) Ergoline alkaloid biosynthesis pathways in the Clavicipitaceae. Arrows indicate one or more steps catalyzed by products of genes indicated. Arrows and genes in blue indicate steps in synthesis of the first fully cyclized intermediate (skeleton). Variation in the easA gene (underlined) determines whether the ergoline skeleton is festuclavine or agroclavine. Arrows and genes in red indicate steps in decoration of the skeleton to give the variety of ergolines in the Clavicipitaceae. Asterisks indicate genes newly discovered in the genome sequences of C. paspali, N. gansuense var. inebrians and P. ipomoeae. (B) Ergopeptines produced by strains in this study.

Mentions: Even within an alkaloid class, structural variations can profoundly affect pharmacological spectra, as reflected for example in the diverse uses of ergot alkaloids in medicine [14], [30](Figure 2). Ergonovine ( = ergometrine) was long used to aid in childbirth, ergotamine is used for migraines, and, in recent years, 2-bromonated ergocryptine (bromocriptine) has been adopted for treatment of numerous disorders of the central nervous system, such as Parkinsonism and pituitary gland adenomas. In contrast, lysergic acid diethylamide (LSD), a semisynthetic ergot alkaloid originally developed as an antidepressant, is the most potent hallucinogen known [31], and was a major factor in the drug culture of the 1960's and 1970's. Historic episodes of mass poisoning in humans have resulted from contamination of grains with ergots (the resting structures of Claviceps species) [32], and the effects vary depending on which alkaloids are present. Symptoms range from the disfiguring dry gangrene of St. Anthony's fire to convulsions and hallucinations such as those associated with the Salem witch trials [33]. For example, outbreaks of convulsive ergotism in India in the late 1970's were due to Claviceps fusiformis producing mainly elymoclavine [34], while Ethiopia experienced a gangrenous ergotism outbreak in 1978 caused by C. purpurea producing ergopeptines [35].


Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci.

Schardl CL, Young CA, Hesse U, Amyotte SG, Andreeva K, Calie PJ, Fleetwood DJ, Haws DC, Moore N, Oeser B, Panaccione DG, Schweri KK, Voisey CR, Farman ML, Jaromczyk JW, Roe BA, O'Sullivan DM, Scott B, Tudzynski P, An Z, Arnaoudova EG, Bullock CT, Charlton ND, Chen L, Cox M, Dinkins RD, Florea S, Glenn AE, Gordon A, Güldener U, Harris DR, Hollin W, Jaromczyk J, Johnson RD, Khan AK, Leistner E, Leuchtmann A, Li C, Liu J, Liu J, Liu M, Mace W, Machado C, Nagabhyru P, Pan J, Schmid J, Sugawara K, Steiner U, Takach JE, Tanaka E, Webb JS, Wilson EV, Wiseman JL, Yoshida R, Zeng Z - PLoS Genet. (2013)

Ergot alkaloids and summary of biosynthesis pathway.(A) Ergoline alkaloid biosynthesis pathways in the Clavicipitaceae. Arrows indicate one or more steps catalyzed by products of genes indicated. Arrows and genes in blue indicate steps in synthesis of the first fully cyclized intermediate (skeleton). Variation in the easA gene (underlined) determines whether the ergoline skeleton is festuclavine or agroclavine. Arrows and genes in red indicate steps in decoration of the skeleton to give the variety of ergolines in the Clavicipitaceae. Asterisks indicate genes newly discovered in the genome sequences of C. paspali, N. gansuense var. inebrians and P. ipomoeae. (B) Ergopeptines produced by strains in this study.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585121&req=5

pgen-1003323-g002: Ergot alkaloids and summary of biosynthesis pathway.(A) Ergoline alkaloid biosynthesis pathways in the Clavicipitaceae. Arrows indicate one or more steps catalyzed by products of genes indicated. Arrows and genes in blue indicate steps in synthesis of the first fully cyclized intermediate (skeleton). Variation in the easA gene (underlined) determines whether the ergoline skeleton is festuclavine or agroclavine. Arrows and genes in red indicate steps in decoration of the skeleton to give the variety of ergolines in the Clavicipitaceae. Asterisks indicate genes newly discovered in the genome sequences of C. paspali, N. gansuense var. inebrians and P. ipomoeae. (B) Ergopeptines produced by strains in this study.
Mentions: Even within an alkaloid class, structural variations can profoundly affect pharmacological spectra, as reflected for example in the diverse uses of ergot alkaloids in medicine [14], [30](Figure 2). Ergonovine ( = ergometrine) was long used to aid in childbirth, ergotamine is used for migraines, and, in recent years, 2-bromonated ergocryptine (bromocriptine) has been adopted for treatment of numerous disorders of the central nervous system, such as Parkinsonism and pituitary gland adenomas. In contrast, lysergic acid diethylamide (LSD), a semisynthetic ergot alkaloid originally developed as an antidepressant, is the most potent hallucinogen known [31], and was a major factor in the drug culture of the 1960's and 1970's. Historic episodes of mass poisoning in humans have resulted from contamination of grains with ergots (the resting structures of Claviceps species) [32], and the effects vary depending on which alkaloids are present. Symptoms range from the disfiguring dry gangrene of St. Anthony's fire to convulsions and hallucinations such as those associated with the Salem witch trials [33]. For example, outbreaks of convulsive ergotism in India in the late 1970's were due to Claviceps fusiformis producing mainly elymoclavine [34], while Ethiopia experienced a gangrenous ergotism outbreak in 1978 caused by C. purpurea producing ergopeptines [35].

Bottom Line: Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals.We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids.We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, USA. Schardl@uky.edu

ABSTRACT
The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.

Show MeSH
Related in: MedlinePlus