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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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Loline alkaloid biosynthesis loci (LOL) in epichloae and the homologous loci in other Clavicipitaceae.LOL genes are indicated by single letters, whereby F = lolF, C = lolC, and so forth. Features are indicated as in Figure 7. Double-slash marks (//) indicate sequence gaps within scaffolds of the assembled E. festucae E2368 genome sequence. Genes for the first fully cyclized intermediate, NANL, are indicated in blue, and those for subsequent chemical decorations are shown in red. The major pathway end-product for each strain is listed at the right of its map, abbreviated as indicated in Figure 4, and in bold for those confirmed in this study.
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pgen-1003323-g009: Loline alkaloid biosynthesis loci (LOL) in epichloae and the homologous loci in other Clavicipitaceae.LOL genes are indicated by single letters, whereby F = lolF, C = lolC, and so forth. Features are indicated as in Figure 7. Double-slash marks (//) indicate sequence gaps within scaffolds of the assembled E. festucae E2368 genome sequence. Genes for the first fully cyclized intermediate, NANL, are indicated in blue, and those for subsequent chemical decorations are shown in red. The major pathway end-product for each strain is listed at the right of its map, abbreviated as indicated in Figure 4, and in bold for those confirmed in this study.

Mentions: The loline alkaloid biosynthesis (LOL) genes were found only in the sequenced genomes of epichloae that produce lolines, and a remnant LOL cluster was identified in an additional epichloid strain. Figure 9 compares the LOL clusters with the two clusters previously characterized in the hybrid endophyte Neotyphodium uncinatum E167 [42]. In the periphery of the LOL locus of E. festucae E2368 were two divergently transcribed, newly discovered genes designated lolN and lolM. Orthologous lolN and lolM genes were also identified in survey sequencing of E167, which has a similar loline alkaloid profile to that of E2368, adding support to the hypothesis that these genes specify certain loline-decorating steps. Scaffolding and long-range physical mapping confirmed and extended previous analysis of large-insert clones [62], indicating that the LOL gene order in E2368 was similar to that in E167. In E2368, 10 of the 11 LOL genes were in pairs of divergently transcribed genes. In the other strains the precise LOL-gene orders were not completely elucidated, but no rearrangements within the cluster were evident. However, orientation of the LOL clusters relative to flanking housekeeping genes, nsfA and lteA, were not conserved. Also, several loline-alkaloid producers had missing or inactive decoration genes (lolN, lolM, and lolP). The LOL cluster of E. brachyelytri E4804, which accumulates AcAP without an ether bridge, had an inactive lolO gene due to an internal deletion, and also lacked functional lolN, lolM, and lolP genes.


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)

Loline alkaloid biosynthesis loci (LOL) in epichloae and the homologous loci in other Clavicipitaceae.LOL genes are indicated by single letters, whereby F = lolF, C = lolC, and so forth. Features are indicated as in Figure 7. Double-slash marks (//) indicate sequence gaps within scaffolds of the assembled E. festucae E2368 genome sequence. Genes for the first fully cyclized intermediate, NANL, are indicated in blue, and those for subsequent chemical decorations are shown in red. The major pathway end-product for each strain is listed at the right of its map, abbreviated as indicated in Figure 4, and in bold for those confirmed in this study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585121&req=5

pgen-1003323-g009: Loline alkaloid biosynthesis loci (LOL) in epichloae and the homologous loci in other Clavicipitaceae.LOL genes are indicated by single letters, whereby F = lolF, C = lolC, and so forth. Features are indicated as in Figure 7. Double-slash marks (//) indicate sequence gaps within scaffolds of the assembled E. festucae E2368 genome sequence. Genes for the first fully cyclized intermediate, NANL, are indicated in blue, and those for subsequent chemical decorations are shown in red. The major pathway end-product for each strain is listed at the right of its map, abbreviated as indicated in Figure 4, and in bold for those confirmed in this study.
Mentions: The loline alkaloid biosynthesis (LOL) genes were found only in the sequenced genomes of epichloae that produce lolines, and a remnant LOL cluster was identified in an additional epichloid strain. Figure 9 compares the LOL clusters with the two clusters previously characterized in the hybrid endophyte Neotyphodium uncinatum E167 [42]. In the periphery of the LOL locus of E. festucae E2368 were two divergently transcribed, newly discovered genes designated lolN and lolM. Orthologous lolN and lolM genes were also identified in survey sequencing of E167, which has a similar loline alkaloid profile to that of E2368, adding support to the hypothesis that these genes specify certain loline-decorating steps. Scaffolding and long-range physical mapping confirmed and extended previous analysis of large-insert clones [62], indicating that the LOL gene order in E2368 was similar to that in E167. In E2368, 10 of the 11 LOL genes were in pairs of divergently transcribed genes. In the other strains the precise LOL-gene orders were not completely elucidated, but no rearrangements within the cluster were evident. However, orientation of the LOL clusters relative to flanking housekeeping genes, nsfA and lteA, were not conserved. Also, several loline-alkaloid producers had missing or inactive decoration genes (lolN, lolM, and lolP). The LOL cluster of E. brachyelytri E4804, which accumulates AcAP without an ether bridge, had an inactive lolO gene due to an internal deletion, and also lacked functional lolN, lolM, and lolP genes.

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