Loline alkaloid: Difference between revisions
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==Mechanism of action== |
==Mechanism of action== |
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Lolines are insecticidal and deterrent to a broad range of insects, including species in the [[Hemiptera]], [[Homoptera]], [[Coleoptera]], [[Hymenoptera]], [[Lepidoptera]], and [[Blattaria]], such as, for example, bird cherry-oat aphid (genus [[Rhopalosiphum]]), [[large milkweed bug]] (''Oncopeltus fasciatus''), and [[American cockroach]] (''Periplaneta americana'').<ref name="Schardl et al 2007"/><ref name="Dahlman et al 1991"> {{cite book |author=Dahlman DL, Eichenseer H, Siegel MR|editors= P Barbosa, VA Krischnik, CG Jones|title= Microbial mediation of plant-herbivore interactions|publisher=John Wiley & Sons |date=1991|pages=227-252 |chapter=Chemical perspectives of endophyte–grass interactions and their implications to insect herbivory |isbn=0-471-61324-X}}</ref> [[LC50|LC<sub>50</sub>]] values of ''N''-formylloline or ''N''-acetylloline from grass seed extracts are 1-20 µg/ml for aphids and milkweed bugs and impair insect development and [[fecundity]] and cause avoidance of loline-containing grass tissues.<ref name="Dahlman et al 1991"/> However, results of feeding tests with grass extracts are occasionally difficult to interpret due to the presence of other endophyte alkaloids in these extracts,<ref name="Schardl et al 2007"/> and the exact mechanism of action of the lolines causing insect deterrence and death are unknown. The lolines may be [[Neurotoxin|neurotoxic]] to the insects, and different lolines display differences in insect toxicity; for example, ''N''-formylloline (see Fig. 2), which occurs in higher concentrations in endophyte-infected grass plants,<ref name="Dahlman et al 1991"/> has greater insect toxicity than some other lolines, which occur at lower concentrations in the grass plant.<ref name="Schardl et al 2007"/> |
Lolines are insecticidal and deterrent to a broad range of insects, including species in the [[Hemiptera]], [[Homoptera]], [[Coleoptera]], [[Hymenoptera]], [[Lepidoptera]], and [[Blattaria]], such as, for example, bird cherry-oat aphid (genus [[Rhopalosiphum]]), [[large milkweed bug]] (''Oncopeltus fasciatus''), and [[American cockroach]] (''Periplaneta americana'').<ref name="Schardl et al 2007"/><ref name="Dahlman et al 1991"> {{cite book |author=Dahlman DL, Eichenseer H, Siegel MR|editors= P Barbosa, VA Krischnik, CG Jones|title= Microbial mediation of plant-herbivore interactions|publisher=John Wiley & Sons |date=1991|pages=227-252 |chapter=Chemical perspectives of endophyte–grass interactions and their implications to insect herbivory |isbn=0-471-61324-X}}</ref> [[LC50|LC<sub>50</sub>]] values of ''N''-formylloline or ''N''-acetylloline from grass seed extracts are 1-20 µg/ml for aphids and milkweed bugs and impair insect development and [[fecundity]] and cause avoidance of loline-containing grass tissues.<ref name="Dahlman et al 1991"/> However, results of feeding tests with grass extracts are occasionally difficult to interpret due to the presence of other endophyte alkaloids in these extracts,<ref name="Schardl et al 2007"/> and the exact mechanism of action of the lolines causing insect deterrence and death are unknown. The lolines may be [[Neurotoxin|neurotoxic]] to the insects, and different lolines display differences in insect toxicity; for example, ''N''-formylloline (see Fig. 2), which occurs in higher concentrations in endophyte-infected grass plants,<ref name="Dahlman et al 1991"/> has greater insect toxicity than some other lolines, which occur at lower concentrations in the grass plant.<ref name="Schardl et al 2007"/> So, the differences in the chemical groups at the C-1-amine result in different levels of bioactivity. |
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[[Image: N-formylloline structure.png|thumb|left|Figure 2. ''N''-formylloline, one of the most abundant lolines in endophyte-infected grasses.]] |
[[Image: N-formylloline structure.png|thumb|left|Figure 2. ''N''-formylloline, one of the most abundant lolines in endophyte-infected grasses.]] |
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The tall fescue endophyte, ''[[Neotyphodium coenophialum|N. coenophialum]]'', has been associated with enhanced resistance to the migratory root-endoparasitic nematode, ''[[Pratylenchus scribneri]]''. Interestingly, at low concentrations ''N''-formylloline serves as a chemoattractant for this nematode, but it is a repellant at higher concentrations.<ref name="Bacetty et al 2009">{{cite journal|author= Bacetty A, Snook M, Glenn A, Noe J, Nagabhyru P, Bacon C|year=2009|title=Chemotaxis disruption in ''Pratylenchus scribneri'' by tall fescue root extracts and alkaloids|journal = [[Journal of Chemical Ecology (journal)| Journal of Chemical Ecology]]|volume=35|pages=844–850|doi=10.1007/s10886-009-9657-x}}</ref> Ergot alkaloids also have repellent and immobilizing effects on ''P. scribneri'',<ref name="Bacetty et al 2009"/> and an endophyte of perennial ryegrass lacking lolines, and genetically engineered to produce no ergot alkaloids, exhibits resistance to this nematode.<ref name="Panaccione et al 2006">{{cite journal|author= Panaccione DG, Kotcon JB, Schardl CL, Johnson RD, Morton JB|year=2006|title= Ergot alkaloids are not essential for endophytic fungus-associated population suppression of the lesion nematode, ''Pratylenchus scribneri,'' on perennial ryegrass|journal = [[Nematology (journal)| Nematology]]|volume=8|pages=583–590|doi=10.1163/156854106778614074}}</ref> Therefore, the relative importance of these alkaloids to nematode resistance remains to be clarified. |
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Because the epichloae endophytes—notably ''[[Neotyphodium coenophialum|N. coenophialum]]'' infecting ''[[Lolium arundinaceum]]'' (syn. ''Festuca arundinacea'', tall fescue)—commonly also produce several compounds, e.g., [[ergot alkaloid]]s and [[indole]]–[[diterpenoid]]s that are toxic to mammalian herbivores and are often difficult to detect, the lolines, which can occur at very high levels in grass tissues,<ref name="Schardl et al 2007"/> were initially associated also with toxicity to [[Mammal|mammalian]] herbivores.<ref name="Jackson et al 1984">{{cite journal|author=Jackson, JA, Hemken, RW, Boling, JA, Harmon, RJ, Buckner, RC, Bush, LP| year=1984|title=Loline alkaloids in tall fescue hay and seed and their relationship to summer fescue toxicosis|journal =Journal of Dairy Science|volume=64|pages=102–109|url=http://jds.fass.org/cgi/reprint/67/1/104?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&title=loline&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT }}</ref> In particular, the lolines were originally thought to be responsible for toxic symptoms called ''fescue toxicosis'' displayed by [[livestock]] grazing on endophyte–infected grasses.<ref name="Jackson et al 1984"/> However, subsequently it was demonstrated that fescue toxicosis (also called summer syndrome) is caused by ergot alkaloids that are also produced by several grass endophytes including ''N. coenophialum'' (which produces both lolines and ergot alkaloids),<ref name="Porter et al 1992">{{cite journal|author=Porter JK, Thompson FN| year=1992|title=Effects of fescue toxicosis on reproduction in livestock|journal = [[Journal of Animal Science]]|volume=70|pages=1594-1603|pmid= 1526927|url=http://jas.fass.org/cgi/reprint/70/5/1594}}</ref> and that lolines had only very small physiological effects on mammalians feeders even at high doses.<ref name="Jackson et al 1996">{{cite journal|author=Jackson JA, Varney DR, Petroski RJ, Powell RG, Bush LP, Siegel MR, Hemken RW, Zavos PM| year=1996|title=Physiological responses of rats fed loline and ergot alkaloids from endophyte-infected tall fescue|journal = [[Drug and Chemical Toxicology]]|volume=19|pages=85-96|pmid=8804555|doi= 10.3109/01480549609002198 }}</ref> Another group of alkaloids, the [[Pyrrolizidine alkaloid|senecio-type]] alkaloids, which are produced by various plants and which—like the lolines—possess a pyrrolizidine ring, exhibit strong [[hepatotoxicity]].<ref name="Fu et al 2004">{{cite journal|author=Fu PP, Xia Q, Lin G, Chou MW| year=2004|title=Pyrrolizidine alkaloids--genotoxicity, metabolism enzymes, metabolic activation, and mechanisms|journal = Drug Metabolism Reviews|volume=36|pages=1-55|pmid=15072438|doi= 10.1081/DMR-120028426}}</ref> This is due to the [[Covalent bond|double bond]] between C-1 and C-2 in the plant pyrrolizidine ring structure <ref name="Fu et al 2004"/> that is absent in the lolines, which are not hepatotoxic. The lolines have been suggested to inhibit seed germination or growth of other plants ([[allelopathy]]),<ref name="Petroski et al 1990">{{cite journal|author=Petroski RJ, Dornbos, DL, Powell RG| year=1990|title=Germination and growth inhibition of annual ryegrass (Lolium multiflorum L.) and alfalfa (Medicago sativa L.) by loline alkaloids and synthetic N-acylloline derivatives|journal = Journal of Agricultural and Food Chemistry|volume=38|pages=1716–1718|doi=10.1021/jf00098a019}}</ref> and to increased resistance of infected grasses against [[drought]], but such effects have not been substantiated under realistic conditions.<ref name="Schardl et al 2007"/><ref name="Bush et al 1997">{{cite journal|author=Bush LP, Wilkinson HH, Schardl CL| year=1997|title=Bioprotective alkaloids of grass-fungal endophyte symbioses|journal = [[Plant Physiology (journal)| Plant Physiology]]|volume=114|pages=1-7|pmid= 12223685 |url= http://www.plantphysiol.org/cgi/reprint/114/1/1 }}</ref> |
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==Production and distribution in the grass plant== |
==Production and distribution in the grass plant== |
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Revision as of 18:58, 4 October 2009
Loline alkaloids, or 1-aminopyrrolizidines (lolines), are natural products with several unique biological and chemical characteristics. The lolines are insecticidal and insect-deterrent compounds in grasses infected by endophytic fungal symbionts of the genus Epichloë (anamorphic species: Neotyphodium). The lolines increase resistance of the grass plant to insect herbivores, and they may also protect the plant from environmental stresses such as drought and spatial competition. They are chemically defined by a saturated pyrrolizidine ring structure, a primary amine at the C-1 carbon, and by an internal ether bridge—a hallmark feature of the lolines, which is uncommon in organic compounds—joining two distant ring (C-2 and C-7) carbons (see Fig. 1). Different substituents at the C-1 amine, such as methyl, formyl, and acetyl groups, yield loline species that have variable bioactivity against insects. Lolines have also been identified in some other plant species; namely, Adenocarpus species Fabaceae and Argyreia mollis Convolvulaceae).
Discovery
A member of the loline alkaloids was first isolated and its elemental composition determined in 1892 from the grass Lolium temulentum and assigned the name temuline (later renamed to norloline). (Reviewed by Schardl et al (2007).)[1] Later studies in the 1950s and 1960s by Russian researchers established the name loline and identified the characteristic 2,7 ether bridge.[1] Since then the analytical methods for purification and analysis of the lolines have been refined and several different loline species identified in many Lolium and related grasses infected by the Epichloë/Neotyphodium (epichloae) grass endophytes.[2][3] Lolines are absent in grass plants uninfected by the endophytes, and not all endophytes produce the lolines.[1] Because of the very intimate association of plant and endophyte and difficulties to reproduce the symbiotic conditions and production of the lolines in vitro, it was long unknown if the fungus was the producer of the lolines, or if they were synthesized in the plant in response to infection. It was demonstrated only recently that the endophyte Neotyphodium uncinatum can produce lolines in chemically defined growth media,[4] which suggests that the endophyte is also the producer of the lolines in the grass plant. Besides endophyte–grass symbiota, lolines have also been reported from some plants in several plant families,[5][6] suggesting a more widespread occurrence of these compounds in nature.
Mechanism of action
Lolines are insecticidal and deterrent to a broad range of insects, including species in the Hemiptera, Homoptera, Coleoptera, Hymenoptera, Lepidoptera, and Blattaria, such as, for example, bird cherry-oat aphid (genus Rhopalosiphum), large milkweed bug (Oncopeltus fasciatus), and American cockroach (Periplaneta americana).[1][7] LC50 values of N-formylloline or N-acetylloline from grass seed extracts are 1-20 µg/ml for aphids and milkweed bugs and impair insect development and fecundity and cause avoidance of loline-containing grass tissues.[7] However, results of feeding tests with grass extracts are occasionally difficult to interpret due to the presence of other endophyte alkaloids in these extracts,[1] and the exact mechanism of action of the lolines causing insect deterrence and death are unknown. The lolines may be neurotoxic to the insects, and different lolines display differences in insect toxicity; for example, N-formylloline (see Fig. 2), which occurs in higher concentrations in endophyte-infected grass plants,[7] has greater insect toxicity than some other lolines, which occur at lower concentrations in the grass plant.[1] So, the differences in the chemical groups at the C-1-amine result in different levels of bioactivity.
The tall fescue endophyte, N. coenophialum, has been associated with enhanced resistance to the migratory root-endoparasitic nematode, Pratylenchus scribneri. Interestingly, at low concentrations N-formylloline serves as a chemoattractant for this nematode, but it is a repellant at higher concentrations.[8] Ergot alkaloids also have repellent and immobilizing effects on P. scribneri,[8] and an endophyte of perennial ryegrass lacking lolines, and genetically engineered to produce no ergot alkaloids, exhibits resistance to this nematode.[9] Therefore, the relative importance of these alkaloids to nematode resistance remains to be clarified.
Because the epichloae endophytes—notably N. coenophialum infecting Lolium arundinaceum (syn. Festuca arundinacea, tall fescue)—commonly also produce several compounds, e.g., ergot alkaloids and indole–diterpenoids that are toxic to mammalian herbivores and are often difficult to detect, the lolines, which can occur at very high levels in grass tissues,[1] were initially associated also with toxicity to mammalian herbivores.[10] In particular, the lolines were originally thought to be responsible for toxic symptoms called fescue toxicosis displayed by livestock grazing on endophyte–infected grasses.[10] However, subsequently it was demonstrated that fescue toxicosis (also called summer syndrome) is caused by ergot alkaloids that are also produced by several grass endophytes including N. coenophialum (which produces both lolines and ergot alkaloids),[11] and that lolines had only very small physiological effects on mammalians feeders even at high doses.[12] Another group of alkaloids, the senecio-type alkaloids, which are produced by various plants and which—like the lolines—possess a pyrrolizidine ring, exhibit strong hepatotoxicity.[13] This is due to the double bond between C-1 and C-2 in the plant pyrrolizidine ring structure [13] that is absent in the lolines, which are not hepatotoxic. The lolines have been suggested to inhibit seed germination or growth of other plants (allelopathy),[14] and to increased resistance of infected grasses against drought, but such effects have not been substantiated under realistic conditions.[1][15]
Production and distribution in the grass plant
Lolines are produced by several grass–endophyte symbioses involving epichloae species, often along with other bioactive metabolites including ergot alkaloids and indole diterpenoids, and the unusual pyrrolopyrazine alkaloid, peramine, which is not found in other biological communities or organisms. However, the lolines are produced at levels that can exceed 10 mg/g grass tissue (ranging from 2–20,000 µg/g[16][1]), which are >1000-fold higher than the concentrations of the other endophyte alkaloids.[7] Lolines produced in the grasses Lolium pratense (syn. Festuca pratensis, meadow fescue) and tall fescue infected by N. uncinatum and N. coenophialum (see Fig. 3), respectively, exhibit variable concentrations in grass tissues.[2][16] Higher loline concentrations (100–1000 µg/g) are present in the seeds and in younger leaf tissues, and the lolines display seasonal changes in concentration levels throughout the plant.[16] The latter appear to be due to the seasonal appearance of tissues, such as flowering stems and seeds, that have high loline concentrations.[16] Enrichment of lolines in younger leaves appears to be responsible for a marked increase in loline concentration in grass tissues regrown after defoliation and clipping of plants, but loline increases resembling inducible plant defense responses have also been reported.[17][18] The differences in loline levels among grass tissues colonized by the endophyte appear to be due chiefly to provide greater protection of newly grown grass tissues or embryonic tissues against attacks by insect herbivores and feeders.[16] Amino acids supplied by the plant to the fungus appear to be a major factor controlling loline production in the symbiosis such that locally increased concentrations of amino acids that are loline alkaloid precursors increase the biosynthesis of the lolines, e.g. in young leaves.[17]
Biosynthesis
The lolines have structural similarities to pyrrolizidine alkaloids produced by many plants, notably the necine ring containing a tertiary amine. This led to the early hypothesis that the biosynthesis of the lolines is similar to that of the plant pyrrolizidines, which are made from polyamines.[19] However, feeding carbon isotope–labeled amino acids or related molecules to pure cultures of the loline-producing fungus N. uncinatum recently demonstrated that the loline alkaloid pathway is fundamentally different from that of the plant pyrrolizidines.[1] The feeding studies showed that lolines are formed in several biosynthetic steps from the amino acid precursors, L-proline and L-homoserine.[20] In the proposed first step in loline biosynthesis, these two amino acids are coupled in a condensation reaction linking the γ-carbon in homoserine to the secondary amine in proline in a PLP–type enzyme–catalyzed reaction.[21] Further steps in loline biosynthesis are thought to proceed with sequential PLP-enzyme-catalyzed and oxidative decarboxylations of the carboxy groups in the homoserine and proline moieties, respectively, cyclization to form the core loline ring structure, and oxidation of the C-2 and C-7 carbons to give the oxygen bridge spanning the two pyrrolizidine rings.[1][22]
Genetic studies agree with the biosynthetic routes established in the precursor-feeding experiments.[1] AFLP-based studies using crosses between strains of the endophyte, Epichloë festucae, that differed in the capacity to produce lolines showed that loline production and loline-enhanced protection of the grass, Lolium giganteum, from feeding by the aphid, Rhopalosiphum padi, segregated in a Mendelian fashion.[23] The presence of a single locus for loline production was confirmed by the finding that loline-producing epichloae endophytes contain a gene cluster (LOL cluster) of at least nine genes.[24] The LOL genes are greatly and coordinately upregulated during loline alkaloid production,[22] and experimental genetic tests involving manipulation of selected LOL genes by RNA interference and gene knockout have confirmed the involvement of two genes in loline alkaloid biosynthesis.[25][26] These tests and similarities in the peptide sequences of the proteins encoded by these genes to known enzymes indicated that one gene, termed lolC, is likely required for the first step in loline biosynthesis (condensation of L-proline and L-homoserine),[25] and another gene, lolP —likely encoding a cytochrome P450 monooxygenase—, for oxygenation of one methyl group on the C-1 amine of N-methylloline, which gives the most abundant loline in many grass–endophyte symbiota, N-formylloline.[26]
References
- ^ a b c d e f g h i j k l m Schardl CL, Grossman RB, Nagabhyru P, Faulkner JR, Mallik UP (2007). "Loline alkaloids: currencies of mutualism". Phytochemistry. 68: 980–996. doi:10.1016/j.phytochem.2007.01.010.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Yates, SG, Petroski, RJ, Powell RG (1990). "Analysis of loline alkaloids in endophyte-infected tall fescue by capillary gas chromatography". Journal of Agricultural and Food Chemistry. 38: 182–185. doi:10.1021/jf00091a040.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Siegel, MR, Latch, GCM., Bush, LP, Fannin, FF, Rowan, D., Tapper, BA, Bacon, CW, Johnson, MC (1990). "Fungal endophyte-infected
grasses: alkaloid accumulation and aphid response". Journal of Chemical Ecology. 16: 3301–3315. doi:10.1007/BF00982100.
{{cite journal}}: line feed character in|title=at position 26 (help)CS1 maint: multiple names: authors list (link) - ^ Blankenship JD, Spiering MJ, Wilkinson HH, Fannin FF, Bush LP, Schardl CL (2001). "Production of loline alkaloids by the grass endophyte, Neotyphodium uncinatum, in defined media". Phytochemistry. 58: 395–401. doi:10.1016/S0031-9422(01)00272-2. PMID 11557071.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Tofern, B, Kaloga, M, Witte, L, Hartmann, T, Eich, E (1999). "Occurrence of loline alkaloids in Argyreia mollis (Convolvulaceae)". Phytochemistry. 51: 1177–1180. doi:10.1016/S0031-9422(99)00121-1.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Veen, G, Greinwald, R, Canto, P, Witte, L, Czygan, FC (1992). "Alkaloids of Adenocarpus hispanicus (Lam.) DC varieties". Zeitschrift für Naturforschung. 47: 341–345.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c d Dahlman DL, Eichenseer H, Siegel MR (1991). "Chemical perspectives of endophyte–grass interactions and their implications to insect herbivory". Microbial mediation of plant-herbivore interactions. John Wiley & Sons. pp. 227–252. ISBN 0-471-61324-X.
{{cite book}}: Unknown parameter|editors=ignored (|editor=suggested) (help)CS1 maint: multiple names: authors list (link) - ^ a b Bacetty A, Snook M, Glenn A, Noe J, Nagabhyru P, Bacon C (2009). "Chemotaxis disruption in Pratylenchus scribneri by tall fescue root extracts and alkaloids". Journal of Chemical Ecology. 35: 844–850. doi:10.1007/s10886-009-9657-x.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Panaccione DG, Kotcon JB, Schardl CL, Johnson RD, Morton JB (2006). "Ergot alkaloids are not essential for endophytic fungus-associated population suppression of the lesion nematode, Pratylenchus scribneri, on perennial ryegrass". Nematology. 8: 583–590. doi:10.1163/156854106778614074.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Jackson, JA, Hemken, RW, Boling, JA, Harmon, RJ, Buckner, RC, Bush, LP (1984). "Loline alkaloids in tall fescue hay and seed and their relationship to summer fescue toxicosis". Journal of Dairy Science. 64: 102–109.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Porter JK, Thompson FN (1992). "Effects of fescue toxicosis on reproduction in livestock". Journal of Animal Science. 70: 1594–1603. PMID 1526927.
- ^ Jackson JA, Varney DR, Petroski RJ, Powell RG, Bush LP, Siegel MR, Hemken RW, Zavos PM (1996). "Physiological responses of rats fed loline and ergot alkaloids from endophyte-infected tall fescue". Drug and Chemical Toxicology. 19: 85–96. doi:10.3109/01480549609002198. PMID 8804555.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Fu PP, Xia Q, Lin G, Chou MW (2004). "Pyrrolizidine alkaloids--genotoxicity, metabolism enzymes, metabolic activation, and mechanisms". Drug Metabolism Reviews. 36: 1–55. doi:10.1081/DMR-120028426. PMID 15072438.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Petroski RJ, Dornbos, DL, Powell RG (1990). "Germination and growth inhibition of annual ryegrass (Lolium multiflorum L.) and alfalfa (Medicago sativa L.) by loline alkaloids and synthetic N-acylloline derivatives". Journal of Agricultural and Food Chemistry. 38: 1716–1718. doi:10.1021/jf00098a019.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Bush LP, Wilkinson HH, Schardl CL (1997). "Bioprotective alkaloids of grass-fungal endophyte symbioses". Plant Physiology. 114: 1–7. PMID 12223685.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c d e Justus, M, Witte, L, Hartmann, T (1997). "Levels and tissue distribution of loline alkaloids in endophyte-infected Festuca pratensis". Phytochemistry. 44: 51–57. doi:10.1016/S0031-9422(96)00535-3.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Zhang, DX, Nagabhyru, P, Schardl CL (2009). "Regulation of a chemical defense against herbivory produced by symbiotic fungi in grass plants". Plant Physiology. 150: 1072–1082. doi:10.1104/pp.109.138222.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Gonthier, TJ, Sullivan, TJ, Brown, KL, Wurtzel, B., Lawal, R., van den Oever, K., Buchan, Z., Bultman, T (2008). "Stroma-forming endophyte Epichloë glyceriae provides wound-inducible herbivore resistance to its grass host". Oikos. 117: 629–633. doi:10.1111/j.0030-1299.2008.16483.x.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Bush, LP, Fannin, FF, Siegel, MR, Dahlman, Burton, HR (1993). "Chemistry, occurrence and biological effects of saturated pyrrolizidine alkaloids associated with endophyte-grass interactions". Agriculture, Ecosystems & Environment. 44: 81–102. doi:10.1016/0167-8809(93)90040-V.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Blankenship JD, Houseknecht JB, Pal S, Bush LP, Grossman RB, Schardl CL (2005). "Biosynthetic precursors of fungal pyrrolizidines, the loline alkaloids". Chembiochem. 6: 1016–1022. doi:10.1002/cbic.200400327. PMID 15861432.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Faulkner JR, Hussaini SR, Blankenship JD, Pal S, Branan BM, Grossman RB, Schardl CL (2006). "On the sequence of bond formation in loline alkaloid biosynthesis". Chembiochem. 7: 1078–1088. doi:10.1002/cbic.200600066. PMID 16755627.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Zhang DX, Stromberg AJ, Spiering MJ, Schardl CL (2009). "Coregulated expression of loline alkaloid-biosynthesis genes in Neotyphodium uncinatum cultures". Fungal Genetics and Biology. 46: 517–530. doi:10.1016/j.fgb.2009.03.010. PMID 19366635.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wilkinson HH, Siegel MR, Blankenship JD, Mallory AC, Bush LP, Schardl CL (2000). "Contribution of fungal loline alkaloids to protection from aphids in a grass-endophyte mutualism". Molecular Plant-Microbe Interactions. 13: 1027–1033. doi:10.1094/MPMI.2000.13.10.1027. PMID 11043464.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kutil BL, Greenwald C, Liu G, Spiering MJ, Schardl CL, Wilkinson HH (2007). "Comparison of loline alkaloid gene clusters across fungal endophytes: predicting the co-regulatory sequence motifs and the evolutionary history". Fungal Genetics and Biology. 44: 1002–10. doi:10.1016/j.fgb.2007.04.003. PMID 17509914.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Spiering MJ, Moon CD, Wilkinson HH, Schardl CL (2005). "Gene clusters for insecticidal loline alkaloids in the grass-endophytic fungus Neotyphodium uncinatum". Genetics. 169: 1403–1414. doi:10.1534/genetics.104.035972. PMID 15654104.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Spiering MJ, Faulkner JR, Zhang DX, Machado C, Grossman RB, Schardl CL (2008). "Role of the LolP cytochrome P450 monooxygenase in loline alkaloid biosynthesis". Fungal Genetics and Biology. 45: 1307–1314. doi:10.1016/j.fgb.2008.07.001. PMID 18655839.
{{cite journal}}: CS1 maint: multiple names: authors list (link)