Abstract
Pyrrolizidine alkaloids are characteristic secondary metabolites of the Asteraceae and some other plant families. They are especially numerous and diverse in the tribe Senecioneae and form a powerful defense mechanism against herbivores. Studies into the evolution of pyrrolizidine alkaloid biosynthesis using Senecio species have identified homospermidine synthase as the enzyme responsible for the synthesis of the first specific intermediate. These studies further indicated that the homospermidine synthase-encoding gene was recruited following gene duplication of deoxyhypusine synthase and that this occurred independently in several different angiosperm lineages. A review of published pyrrolizidine alkaloid data shows that the Senecioneae are characterized by a large qualitative and quantitative variation in pyrrolizidine alkaloid profiles and that these data demonstrate little phylogenetic signal. This suggests that although the first steps of this pathway are highly conserved, the diversification of secondarily derived pyrrolizidine alkaloids is extremely plastic.
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Abbreviations
- cDNA:
-
Complementary DNA
- DHS:
-
Deoxyhypusine synthase
- E. coli :
-
Escherichia coli
- eIF5A:
-
Eukaryotic initiation factor 5A
- HSS:
-
Homospermidine synthase
- J.:
-
Jacobaea
- PA(s):
-
Pyrrolizidine alkaloid(s)
- S.:
-
Senecio
References
Abdelhady MIS, Beuerle T, Ober D (2009) Homospermidine in transgenic tobacco results in considerably reduced spermidine levels but is not converted to pyrrolizidine alkaloid precursors. Plant Mol Biol 71:145–155
Adams R, Gianturco M (1956) Senecio alkaloids: the alkaloids of Senecio brasiliensis, fremonti and ambrosioides. J Am Chem Soc 78:5315–5317
Adams R, Gianturco M (1957) Senecio alkaloids: spartioidine, the alkaloid from Senecio spartioides; stereochemical relationship to other Senecio alkaloids. J Am Chem Soc 79:174–177
Agrawal AA, Fishbein M (2008) Phylogenetic escalation and decline of plant defense strategies. Proc Natl Acad Sci USA 105:10057–10060
Agrawal AA, Salminen J-P, Fishbein M (2009) Phylogenetic trends in phenolic metabolism of milkweeds (Asclepias): evidence for escalation. Evolution 63:663–673
Ahmad W, Ahmad Z, Najamul-Hussain Kazmi S et al (1994) Pyrrolizidine-alkaloid content of the genus Senecio. J Chem Soc Pak 16:64–81
Anke S, Niemüller D, Moll S et al (2004) Polyphyletic origin of pyrrolizidine alkaloids within the Asteraceae. Evidence from differential tissue expression of homospermidine synthase. Plant Physiol 136:4037–4047
Anke S, Gonde D, Kaltenegger E et al (2008) Pyrrolizidine alkaloid biosynthesis in Phalaenopsis orchids: developmental expression of alkaloid-specific homospermidine synthase in root tips and young flower buds. Plant Physiol 148:751–760
Arciniegas A, Pérez Castorena AL, Villaseñor JL et al (2005) Chemical constituents of Senecio procumbens. J Mex Chem Soc 49:284–286
Asada Y, Furuya T (1982) Neosenkirkine and senkirkine from Senecio pierotii. Planta Med 44:182
Asada Y, Furuya T, Shiro M et al (1982) Senecicannabine, a new pyrrolizidine alkaloid from Senecio cannabinifolius. Tetrahedron Lett 23:189–192
Asibal CF, Zalkow LH, Gelbaum LT (1991) Acetylanonamine, a new secopyrrolizidine alkaloid from Senecio anonymus. J Nat Prod 54:1425–1426
Asres K, Sporer F, Wink M (2008) Occurrence of pyrrolizidine alkaloids in three Ethiopian Solanecio species. Biochem Syst Ecol 36:399–407
Bah M, Bye R, Pereda-Miranda R (1994) Hepatotoxic pyrrolizidine alkaloids in the Mexican medicinal plant Packera candidissima (Asteraceae; Senecioneae). J Ethnopharmacol 43:19–30
Bai YL, Benn M, Majak W (1996) Pyrrolizidine alkaloids of three species of Senecio in British Columbia. Planta Med 62:71–72
Bai Y, Benn M, Duke N et al (2006) The alkaloids of Brachyglottis hectori. ARKIVOC III:34–42
Barrero AF, Alvarez-Manzaneda Roldan EJ, Alvarez-Manzaneda Roldan R (1991) Pyrrolizidine alkaloids from Senecio nebrodensis L. Annales de Quimica 87:386–390
Benn M, Gul W (2007) Pyrrolizidine alkaloids in the antipodean genus Brachyglottis (Asteraceae). Biochem Syst Ecol 35:676–681
Benn M, Were O (1992) Ruwenine and ruzorine: pyrrolizidine alkaloids of Senecio ruwenzoriensis. Phytochemistry 31:3295–3296
Benn MH, Mathenge S, Munavu RM et al (1995) The principal alkaloid of Senecio schweinfurthii. Phytochemistry 40:1327–1329
Bicchi C, Caniato R, Tabacchi R et al (1989) Capillary gas chromatography/positive and negative ion chemical ionization mass spectrometry on pyrrolizidine alkaloids of Senecio inaequidens using ammonia and hydroxyl ions as the reagent species. J Nat Prod 52:32–41
Bicchi C, Rubiolo P, Frattini C et al (1991) Off-line supercritical fluid extraction and capillary gas chromatography of pyrrolizidine alkaloids in Senecio species. J Nat Prod 54:941–945
Bohlmann F, Zdero C, Bergert D et al (1979) Neue Furanoeremophilane und weitere Inhaltsstoffe aus südafrikanischen Senecio-Arten. Phytochemistry 18:79–93
Bohlmann F, Gupta RK, Jakupovic J (1981) An acylpyrrole derivative and further constituents from Jamaican representatives of the tribe Senecioneae. Phytochemistry 20:831–832
Bohlmann F, Zdero C, Jakupovic J et al (1986) Further pyrrolizidine alkaloids and furoeremophilanes from Senecio species. Phytochemistry 25:1151–1159
Boppré M, Colegate SM, Edgar JA et al (2008) Hepatotoxic pyrrolizidine alkaloids in pollen and drying-related implications for commercial processing of bee pollen. J Agric Food Chem 56:5662–5672
Böttcher F, Adolph RD, Hartmann T (1993) Homospermidine synthase, the first pathway-specific enzyme in pyrrolizidine alkaloid biosynthesis. Phytochemistry 32:679–689
Böttcher F, Ober D, Hartmann T (1994) Biosynthesis of pyrrolizidine alkaloids: putrescine and spermidine are essential substrates of enzymatic homospermidine formation. Can J Chem 72:80–85
Bourauel T, Plassmeier C, Roeder E (1998) Pyrrolizidine alkaloids from Senecio nevadensis. J Nat Toxins 7:87–93
Bredenkamp MW, Wiechers A, van Rooyen PH (1985) A new pyrrolizidine alkaloid from Senecio latifolius DC. Tetrahedron Lett 26:929–932
Bridgham JT, Brown JE, Rodriguez-Mari A et al. (2008) Evolution of a new function by degenerative mutation in cephalochordate steroid receptors. PLoS Genet 4 doi 10.1371/s1000191
Briggs LH, Crambie RC, Candy BJ et al (1965) Alkaloids of New Zealand Senecio species: part II. senkirkine. J Chem Soc 65:2492–2498
Cava MP, Rao KV, Weisbach JA et al (1968) Alkaloids of Cacalia floridana. J Org Chem 33:3570–3573
Chen KY, Liu AY (1997) Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A. Biol Signals 6:105–109
Cheng D-L, Niu J-K, Roeder E (1992) Pyrrolizidine alkaloids from Senecio kaschkarovii. Phytochemistry 31:3671–3672
Chizzola R, Ozelsberger B, Langer T (2000) Variability in chemical constituents in Petasites hybridus from Austria. Biochem Syst Ecol 28:421–432
Chou MW, Fu PP (2006) Formation of DHP-derived DNA adducts in vivo from dietary supplements and Chinese herbal plant extracts containing carcinogenic pyrrolizidine alkaloids. Toxicol Ind Health 22:321–327
Christov V, Evstatieva L (2003) Alkaloid profile of Bulgarian species from genus Senecio L. Z Naturforsch C: Biosci 58c:300–302
Christov V, Mikhova B, Alexandrova R et al (2002a) Alkaloids from the roots of Senecio macedonicus Griseb. Z Naturforsch C: Biosci 57:780–784
Christov VS, Mikhova BP, Evstatieva LN (2002b) Alkaloids from Senecio aquaticus. Fitoterapia 73:171–173
Christov V, Kostova N, Evstatieva L (2005) 6α-Angeloylplatynecine: a new alkaloid from Senecio nemorensis subsp. fuchsii (C. C. Gmelin) Celak. Nat Prod Res 19:389–392
Cooper RA, Bowers RJ, Beckham CJ et al (1996) Preparative separation of pyrrolizidine alkaloids by high-speed counter-current chromatography. J Chromatogr A 732:43–50
Coucourakis ED, Gordon-Gray CG (1970) The Senecio alkaloids. Suggested structures for isoline and bisline, two new alkaloids from Senecio othonniformis Fourcade. J Chem Soc C: Org: 2312–2315
Culvenor CCJ (1978) Pyrrolizidine alkaloids—occurrence and systematic importance in angiosperms. Botaniska Notiser 131:473–486
Culvenor CCJ, Geissman TA (1961) The alkaloids of Senecio mikanioides Otto. Sarracine and sarracine N-oxide. J Org Chem 26:3045–3050
Culvenor CCJ, Smith LW (1955) The alkaloids of Erechtites quadridentata DC. Aust J Chem 8:556–561
Culvenor CCJ, Edgar JA, Smith LW et al (1976) The occurence of senkirkine in Tussilago farfara. Austr J Chem 29:229–230
DaSilva CdM, Bolzan AA, Heinzmann BM (2006) Alcalóides pirrolizidínicos em espécies do gênero Senecio. Quim Nova 29:1047–1053
DePristo MA (2007) The subtle benefits of being promiscuous: adaptive evolution potentiated by enzyme promiscuity. HFSP J 1:94–98
Dominguez DM, Reina M, Santos-Guerra A et al (2008) Pyrrolizidine alkaloids from Canarian endemic plants and their biological effects. Biochem Syst Ecol 36:153–166
Ehmke A, von Borstel K, Hartmann T (1987) Specific uptake of the N-oxides of pyrrolizidine alkaloids by cells, protoplasts, and vacuoles from Senecio cell cultures. In: Marin BP (ed) Plant vacuoles. Plenum Press, New York, pp 301–304
Ehmke A, von Borstel K, Hartmann T (1988) Alkaloid N-oxides as transport and vacuolar storage compounds of pyrrolizidine alkaloids in Senecio vulgaris L. Planta 176:83–90
Ehrlich PR, Raven PH (1964) Butterflies and plants: a study in coevolution. Evolution 18:586–608
Eich E (2007) Solanaceae and convolulaceae: secondary metabolites, biosynthesis, chemotaxonomy, biological and economic significance—a handbook. Springer, Berlin
El-Shazly A (2002) Pyrrolizidine alkaloid profiles of some Senecio species from Egypt. Z Naturforsch C: Biosci 57c:429–433
Fang Z, Chang-hong W, Wan W et al (2008) Quantitative analysis by HPLC-MS of the pyrrolizidine alkaloid adonifoline in Senecio scandens. Phytochem Anal 19:25–31
Freer AA, Kelly HA, Robins DJ (1986) Rosmarinine: a pyrrolizidine alkaloid. Acta Crystallogr C 42:1348–1350
Fröhlich C, Hartmann T, Ober D (2006) Tissue distribution and biosynthesis of 1, 2-saturated pyrrolizidine alkaloids in Phalaenopsis hybrids (Orchidaceae). Phytochem 67:1493–1502
Fu PP, Xia Q, Lin G et al (2004) Pyrrolizidine alkaloids—genotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metab Rev 36:1–55
Gardner DR, Thorne MS, Molyneux RJ et al (2006) Pyrrolizidine alkaloids in Senecio madagascariensis from Australia and Hawaii and assessment of possible livestock poisoning. Biochem Syst Ecol 34:736–744
Gharbo SA, Habib AAM (1969) Phytochemical investigation of Egyptian Senecio. Part 2. Alkaloids of Senecio aegyptius, S. desfontainei, S. vulgaris, S. petasitis and S. mikanioides. Lloydia 32:503–508
Glinski JA, Asibal CF, Van Derveer D et al (1988) Anonamine, C19H27NO7, neosenkirkine, C19H27NO6, and hydroxysenkirkine, C19H27NO7.CH3OH. Macrocyclic secopyrrolizidine alkaloids from Senecio anonymus Wood. Acta Crystallogr C 44:1593–1598
González AG, De la Fuente MG, Reina M (1973) Alcaloides de la pirrolizidina I. Alcaloides del Senecio petasites D.C. (Compuesta). Anales de Quimica 69:1343–1345
Gordon-Gray CG (1967) Senecio alkaloids. 19. Isolation of chlorodeoxysceleratine. J Chem Soc C: Org: 781–782
Gordon-Gray CG, Wells RB (1974) Senecio alkaloids—structure and absolute-configuration of swazine. J Chem Soc Perkin Trans I:1556–1561
Grotewold E (2005) Plant metabolic diversity: a regulatory perspective. Trends Plant Sci 10:57–62
Grue MR, Liddell JR (1993) Pyrrolizidine alkaloids from Senecio chrysocoma. Phytochemistry 33:1517–1519
Habermehl GG, Martz W, Tokarnia CH et al (1988) Livestock poisoning in South America by species of the Senecio plant. Toxicon 26:275–286
Habib A-AM (1981) Alkaloids from Senecio aegyptius and S. desfontainei. Planta Med 43:290–292
Hartmann T (1985) Prinzipien des pflanzlichen Sekundärstoffwechsels. Plant Syst Evol 150:15–34
Hartmann T (2004) Plant-derived secondary metabolites as defensive chemicals in herbivorous insects: a case study in chemical ecology. Planta 219:1–4
Hartmann T (2007) From waste products to ecochemicals: fifty years research of plant secondary metabolism. Phytochemistry 68:2831–2846
Hartmann T, Dierich B (1998) Chemical diversity and variation of pyrrolizidine alkaloids of the senecionine type: biological need or coincidence? Planta 206:443–451
Hartmann T, Ober D (2000) Biosynthesis and metabolism of pyrrolizidine alkaloids in plants and specialized insect herbivores. In: Leeper FJ, Vederas JC (eds) Topics in current chemistry. Springer, Berlin, pp 207–244
Hartmann T, Ober D (2008) Defense by pyrrolizidine alkaloids: developed by plants and recruited by insects. In: Schaller A (ed) Induced plant resistance to herbivory. Springer, Berlin, pp 213–231
Hartmann T, Toppel G (1987) Senecionine N-oxide, the primary product of pyrrolizidine alkaloid biosynthesis in root cultures of Senecio vulgaris. Phytochemistry 26:1639–1643
Hartmann T, Witte L (1995) Chemistry, biology and chemoecology of the pyrrolizidine alkaloids. In: Pelletier SW (ed) Alkaloids: chemical and biological perspectives. Pergamon Press, Oxford, pp 155–233
Hartmann T, Zimmer M (1986) Organ-specific distribution and accumulation of pyrrolizidine alkaloids during the life history of two annual Senecio species. J Plant Physiol 122:67–80
Hartmann T, Sander H, Adolph RD et al (1988) Metabolic links between the biosynthesis of pyrrolizidine alkaloids and polyamines in root cultures of Senecio vulgaris. Planta 175:82–90
Hartmann T, Ehmke A, Eilert U et al (1989) Sites of synthesis, translocation and accumulation of pyrrolizidine alkaloid N-oxides in Senecio vulgaris L. Planta 177:98–107
Hartmann T, Witte L, Ehmke A et al (1997) Selective sequestration and metabolism of plant derived pyrrolizidine alkaloids by chrysomelid leaf beetles. Phytochemistry 45:489–497
Hartmann T, Theuring C, Beuerle T et al (2004) Acquired and partially de novo synthesized pyrrolizidine alkaloids in two polyphagous Arctiids and the alkaloid profiles of their larval food-plants. J Chem Ecol 30:229–254
Hartmann T, Kutchan TM, Strack D (2005) Evolution of metabolic diversity. Phytochemistry 66:1198–1199
Heinrich M, Robles M, West JE et al (1998) Ethnopharmacology of Mexican Asteraceae (Compositae). Annu Rev Pharmacol Toxicol 38:539–565
Hirono I, Mori H, Yamada K et al (1977) Carcinogenic activity of petasitenine, a new alkaloid from Petasites japonicus Maxim. J Natl Cancer Inst 58:1155–1156
Hirschmann GS, Jakupovic J (1988) Pyrrolizidine alkaloids from Senecio deferens. Planta Med 54:360
Hol WHG, Van Veen JA (2002) Pyrrolizidine alkaloids from Senecio jacobaea affect fungal growth. J Chem Ecol 28:1763–1772
Hösch G, Wiedenfeld H, Dingermann T et al (1996) A new high performance liquid chromatography method for the simultaneous quantitative analysis of pyrrolizidine alkaloids and their N-oxides in plant material. Phytochem Anal 7:284–288
Hughes AL (1994) The evolution of functionally novel proteins after gene duplication. Proc R Soc Lond B Biol Sci 256:119–124
Ingolfsdóttir K, Hylands PJ (1990) Pyrrolizidine alkaloids in Senecio vulgaris L. growing in Iceland. Acta Pharm Nord 2:343–348
Ji L, Chen Y, Liu T et al (2008) Involvement of Bcl-xL degradation and mitochondrial-mediated apoptotic pathway in pyrrolizidine alkaloids-induced apoptosis in hepatocytes. Toxicol Appl Pharmacol 231:393–400
Jones CG, Firn RD (1991) On the evolution of plant secondary chemical diversity. Phil Trans R Soc London Ser B 333:273–280
Kapadia GJ, Ramdass A, Bada F (1990) Pyrrolizidine alkaloids of Senecio glabellus. Pharm Biol 28:67–71
Klásek A, Reichstein T, Šantavy F (1968) Die Pyrrolizidin-Alkaloide aus Senecio alpinus (L.) Scop., S. subalpinus Koch und S. incanus L. subsp. carniolicus (Willd.) Br.-Bl. Pyrrolizidin-Alkaloide, 13. Mitteilung. Helv Chim Acta 51:1088–1095
Kostova N, Christov V, Cholakova M et al (2006) Pyrrolizidine alkaloids from Bulgarian species of the genus Senecio. J Serb Chem Soc 71:1275–1280
Koulmann A, Seeliger C, Edwards PJB et al (2008) E/Z-Thesinine-O-4′-α-rhamnoside, pyrrolizidine conjugates produced by grasses (Poaceae). Phytochemistry 69:1927–1932
Krebs HC, Carl T, Habermehl GG (1996) Pyrrolizidine alkaloid composition in six brazilian Senecio species. Phytochemistry 43:1227–1229
Kunec EK, Robins DJ (1986) Evidence for different 1-hydroxymethylpyrrolizidines as intermediates in the biosynthesis of retronecine and rosmarinecine. J Chem Soc Chem Commun 250–252
Laing M, Sommerville P (1972) Crystal and molecular structure of methiodide of swazine, an alkaloid from Senecio swaziensis Compton. Tetrahedron Lett 51:5183–5186
Leonard NJ (1959) Senecio alkaloids. In: Manske RHF, Holmes HL (Eds) The alkaloids. Elsevier pp. 108–166
Li S-L, Lin G, Fu PP et al (2008) Identification of five hepatotoxic pyrrolizidine alkaloids in a commonly used traditional Chinese medicinal herb, Herba Senecionis scandentis (Qianliguang). Rapid Commun Mass Spectrom 22:591–602
Liddell JR (1999) Pyrrolizidine alkaloids. Nat Prod Rep 16:499–507
Liddell JR, Logie CG (1993a) 7-Angelyl-1-methylenepyrrolizidines from Senecio chrysocoma. Phytochemistry 34:1198–1199
Liddell JR, Logie CG (1993b) A re-investigation of the alkaloids of Senecio pterophorus. Phytochemistry 34:1629–1631
Liddell JR, Stermitz FR (1994) Pyrrolizidine alkaloids from Trollius laxus. In: Colegate SM, Dorling PR (eds) Plant-assoc. Toxins: agricultural, phytochemical, and ecological aspects Proc Int Symp Poisonous Plants (ISOPP4, 1993). CAB International, Wallingford, pp 217–220
Lin W-Y, Teng C-M, Tsai I-L et al (2000) Anti-platelet aggregation constituents from Gynura elliptica. Phytochemistry 53:833–836
Liu K, Roeder E (1991) Pyrrolizidine alkaloids from Senecio argunensis. Phytochemistry 30:1303–1305
Lock Sing OR (2006) Diversidad química el género Werneria. Rev Soc Quím Perú 72:32–48
Luethy J, Zweifel U, Schlattter C et al (1980) Pyrrolizidine alkaloids in coltsfoot (Tussilago farfara) of various sources. Mitteilungen Geb Lebensm 71:73–80
Luethy J, Zweifel U, Karlhuber B et al (1981) Pyrrolizidine alkaloids of Senecio alpinus L. and their detection in feedingstuffs. J Agric Food Chem 29:302–305
Luethy J, Zweifel U, Schlatter C (1983) Pyrrolizidin-alkaloide in Petasites hybridus L. und P. albus L. Pharm Acta Helv 58:98–100
Macel M, Vrieling K, Klinkhamer PG (2004) Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea. Phytochemistry 65:865–873
Macel M, Bruinsma M, Dijkstra SM et al (2005) Differences in effects of pyrrolizidine alkaloids on five generalist insect herbivore species. J Chem Ecol 31:1493–1508
Mackay MF, Mitrprachachon P, Culvenor CCJ (1985) Hygrophylline, C18H27NO6: a pyrrolizidine alkaloid. Acta Crystallogr C 41:395–397
Maldonado R JI, Arciniegas A, Pérez-Castorena A-L et al (2008) Furanoeremophilanes and other constituents of Pittocaulon bombycophole. Heterocycles 75:3035–3042
Mandic BM, Godevac DN, Beškoski VP et al (2009) Pyrrolizidine alkaloids from seven wild-growing Senecio species in Serbia and Montenegro. J Serb Chem Soc 74:27–34
Manske RHF (1944) The alkaloids. Annu Rev Biochem 13:533–548
Marín-Loaiza JC, Céspedes C, Beuerle T et al (2007) Ceroplastes albolineatus, the first scale insect shown to sequester pyrrolizidine alkaloids from its host-plant Pittocaulon praecox. Chemoecology 17:109–115
Marín-Loaiza JC, Ernst L, Beuerle T et al (2008) Pyrrolizidine alkaloids of the endemic Mexican genus Pittocaulon and assignment of stereoisomeric 1, 2-saturated necine bases. Phytochemistry 69:154–167
Mattocks AR (1968) Toxicity of pyrrolizidine alkaloids. Nature 217:723–728
Mattocks AR (1986) Chemistry and toxicology of pyrrolizidine alkaloids. Academic Press, London
Mattocks AR, Driver E (1987) Toxic actions of senaetnine, a new pyrrolizidine-type alkaloid, in rats. Toxicol Lett 38:315–319
McGaw LJ, Steenkamp V, Eloff JN (2007) Evaluation of Athrixia bush tea for cytotoxicity, antioxidant activity, caffeine content and presence of pyrrolizidine alkaloids. J Ethnopharmacol 110:16–22
Moll S, Anke S, Kahmann U et al (2002) Cell-specific expression of homospermidine synthase, the entry enzyme of the pyrrolizidine alkaloid pathway in Senecio vernalis, in comparison with its ancestor, deoxyhypusine synthase. Plant Physiol 130:47–57
Molyneux RJ, Johnson AE, Roitman JN et al (1979) Chemistry of toxic range plants. Determination of pyrrolizidine alkaloid content and composition in Senecio species by nuclear magnetic resonance spectroscopy. J Agric Food Chem 27:494–499
Mroczek T, Glowniak K (2002) Pyrrolizidine alkaloids. Their chemistry, occurence and significance as natural compounds. In: Rauter AP, Palma FB, Justino J, Araújo ME, Dos Santos SP (eds) Natural products in the new millenium: propspects and industrial application. Kluwer, Dordrecht, pp 1–46
Mroczek T, Glowniak K, Wlaszczyk A (2002) Simultaneous determination of N-oxides and free bases of pyrrolizidine alkaloids by cation-exchange solid-phase extraction and ion-pair high-performance liquid chromatography. J Chromatogr A 949:249–262
Mroczek T, Ndjoko K, Glowniak K et al (2004) On-line structure characterization of pyrrolizidine alkaloids in Onosma stellulatum and Emilia coccinea by liquid chromatography-ion-trap mass spectrometry. J Chromatogr A 1056:91–97
Nawaz HR, Malik A, Muhammad P et al (2000) Chemical constituents of Ajuga parviflora. Z Naturforsch 55b:100–103
Ndjoko K, Wolfender J-L, Roeder E et al (1999) Determination of pyrrolizidine alkaloids in Senecio species by liquid chromatography/thermospray-mass spectrometry and liquid chromatography/nuclear magnetic resonance spectroscopy. Planta Med 65:562–566
Niwa H, Ishiwata H, Kuroda A et al (1983) Farfugine, a new pyrrolizidine alkaloid isolated from Farfugium japonicum Kitam. Chem Lett 12:789–790
Niwa H, Ishiwata H, Yamada K (1985) Isolation of petasitenine, a carcinogenic pyrrolizidine alkaloid from Farfugium japonicum. J Nat Prod 48:1003–1004
Noorwala M, Mohammad FV, Ahmad VU et al (2000) Pyrrolizidine alkaloids from Senecio lorenthii. Fitoterapia 71:618–620
Ober D (2005) Seeing double: gene duplication and diversification in plant secondary metabolism. Trends Plant Sci 10:444–449
Ober D (2010) Gene duplications and the time thereafter—examples from plant secondary metabolism. Plant Biol (in press)
Ober D, Hartmann T (1999a) Deoxyhypusine synthase from tobacco: cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity. J Biol Chem 274:32040–32047
Ober D, Hartmann T (1999b) Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. Proc Natl Acad Sci USA 96:14777–14782
Ober D, Hartmann T (2000) Phylogenetic origin of a secondary pathway: the case of pyrrolizidine alkaloids. Plant Mol Biol 44:445–450
Ober D, Kaltenegger E (2009) Pyrrolizidine alkaloid biosynthesis, evolution of a pathway in plant secondary metabolism. Phytochemistry 70:1687–1695
Ober D, Harms R, Witte L et al (2003) Molecular evolution by change of function: alkaloid-specific homospermidine synthase retained all properties of deoxyhypusine synthase except binding the eIF5A precursor protein. J Biol Chem 278:12805–12812
Paiva JA, Barata LES, Trigo JR (2004) Pyrrolizidine alkaloids in three Senecio species from southern Brazil. Biochem Syst Ecol 32:1219–1222
Park MH, Lee YB, Joe YA (1997) Hypusine is essential for eukaryotic cell proliferation. Biol Signals 6:115–123
Pelser PB, van den Hof K, Gravendeel B et al (2004) The systematic value of morphological characters in Senecio sect. Jacobaea (Asteraceae) as compared to DNA sequences. Syst Bot 29:790–805
Pelser PB, de Vos H, Theuring C et al (2005) Frequent gain and loss of pyrrolizidine alkaloids in the evolution of Senecio section Jacobaea (Asteraceae). Phytochemistry 66:1285–1295
Pelser PB, Nordenstam B, Kadereit JW et al (2007) An ITS phylogeny of tribe Senecioneae (Asteraceae) and a new delimitation of Senecio L. Taxon 56:1077–1104
Pelser PB, Kennedy AH, Tepe EJ et al (2010) Patterns and causes of incongruence between plastid and nuclear Senecioneae (Asteraceae) phylogenies. Am J Bot 97:856–873
Perez-Castorena A-L, Arciniegas A, Alonso RP et al (1998) Callosine, a 3-alkyl-substituted pyrrolizidine alkaloid from Senecio callosus. J Nat Prod 61:1288–1291
Pérez-Castorena A-L, Arciniegas A, Castro A et al (1997) Pyrrolizidine alkaloids from Senecio roseus and Senecio helodes. J Nat Prod 60:1322–1325
Pérez-Castorena A-L, Arciniegas A, Perez R et al (1999a) Iodanthine, a pyrrolizidine alkaloid from Senecio iodanthus and Senecio bracteatuss. J Nat Prod 62:1039–1043
Pérez-Castorena A-L, Arciniegas A, Villaseñor JL et al (1999b) Alkaloids from three Senecio species. Biochem Syst Ecol 27:835–837
Pérez-Castorena A-L, Arciniegas A, Martinez F et al (2000) Pyrrolizidine alkaloids from four Senecio species. Biochem Syst Ecol 28:279–282
Pestchanker MJ, Ascheri MS, Giordano OS (1985) Uspallatine, a pyrrolizidine alkaloid from Senecio uspallatensis. Phytochemistry 24:1622–1624
Pieters LA, Vlietinck AJ (1988) Spartioidine and usaramine, two pyrrolizidine alkaloids from Senecio vulgaris. Planta Med 54:178–179
Qi X, Wu B, Cheng Y et al (2009) Simultaneous characterization of pyrrolizidine alkaloids and N-oxides in Gynura segetum by liquid chromatography/ion trap mass spectrometry. Rapid Commun Mass Spectrom 23:291–302
Ray AC, Williams HJ, Reagor JC (1987) Pyrrolizidine alkaloids from Senecio longilobus and Senecio glabellus. Phytochemistry 26:2431–2433
Reimann A, Nurhayati N, Backenköhler A et al (2004) Repeated evolution of the pyrrolizidine alkaloid-mediated defense system in separate angiosperm lineages. Plant Cell 16:2772–2784
Reina M, Gonzalez-Coloma A, Gutierrez C et al (2000) Defensive chemistry of Senecio miser. J Nat Prod 64:6–11
Rizk A-FM (1990) The pyrrolizidine alkaloids: plant sources and properties. In: Rizk A-FM (ed) Naturally occuring pyrrolizidine alkaloids. CRC Press, Boca Raton, pp 1–89
Robins DJ (1982) The pyrrolizidine alkaloids. Prog Chem Org Nat Prod 41:115–202
Robins DJ (1994) Pyrrolizidine alkaloids. Nat Prod Rep 11:613–619
Roeder E (1995) Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 50:83–98
Roeder E (2000) Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie 55:711–726
Roeder E, Abdel-Ghani A (1990) Pyrrolizidine alkaloids from Petasites paradoxus (Retz.) Baumg. Sci Pharm 58:403–407
Roeder E, Liu K (1991) Pyrrolizidine alkaloids from Senecio integrifolius var. fauriri. Phytochemistry 30:1734–1737
Roeder E, Wiedenfeld H (1977) Isolierung und Strukturaufklärung des Alkaloids Fuchsisenecionin aus Senecio fuchsii. Phytochemistry 16:1462–1463
Roeder E, Wiedenfeld H, Pastewka U (1979) Pyrrolizidinalkaloide aus Senecio vernalis. Planta Med 37:131–136
Roeder E, Wiedenfeld H, Frisse M (1980a) Pyrrolizidinalkaloide aus Senecio doronicum. Phytochemistry 19:1275–1277
Roeder E, Wiedenfeld H, Stengl P (1980b) Das Pyrrolizidinalkaloid O7-Angelylheliotridin aus Senecio ovirensis. Planta Med Suppl 182–184
Roeder E, Wiedenfeld H, Stengl P (1981) Die Pyrrolizidinalkaloide Senecionin und Retrorsin aus Senecio inaequidens. Planta Med 39:412–413
Roeder E, Wiedenfeld H, Hoening A (1983) Pyrrolizidinealkaloide aus Senecio aureus. Planta Med 49:57–59
Roeder E, Wiedenfeld H, Britz-Kirstgen R (1984a) Pyrrolizidine alkaloids from Senecio cacaliaster. Phytochemistry 23:1761–1763
Roeder E, Wiedenfeld H, Knözinger-Fischer P (1984b) Pyrrolizidinalkaloide aus Senecio abrotanifolius, ssp. abrotanifolius und ssp. abrotanifolius var. tiroliensis. Planta Med 2:203–204
Roeder E, Hille T, Wiedenfeld H (1986) Pyrrolizidin-alkaloide von Senecio sylvaticus L. Sci Pharm 54:347–350
Roeder E, Wiedenfeld H, Pfitzer A (1988) Doriasenine, a pyrrolizidine alkaloid from Senecio doria. Phytochemistry 27:4000–4001
Roeder E, Wiedenfeld H, Kersten R (1990) The pyrrolizidine alkaloids of Senecio aquaticus Huds. Sci Pharm 58:1–8
Roeder E, Bourauel T, Theisen I (1992) Pyrrolizidine alkaloids from Werneria nubigena. Nat Toxins 1:81–83
Roeder E, Bourauel T, Kersten R (1993a) Pyrrolizidine alkaloids from Senecio persoonii. Phytochemistry 32:1051–1053
Roeder E, Eckert A, Bourauel T (1993b) Pyrrolizidine alkaloids from Petasites spurius. Pharmazie 48:953–954
Roitman JN (1983) The pyrrolizidine alkaloids of Senecio triangularis. Aust J Chem 36:1203–1213
Romo de Vivar A, Pérez A-L, Arciniegas A et al (1995) Pyrrolizidine alkaloids from Senecio mulgediifolius, two new 13-membered macrocyclic 7, 9-diesters. Tetrahedron Lett 51:12521–12528
Romo de Vivar A, Peréz A-L, Vidales P et al (1996) Pyrrolizidine alkaloids from Senecio jacalensis and Senecio callosus. Biochem Syst Ecol 24:175–176
Romo de Vivar A, Perez-Castorena A-L, Arciniegas A et al (2007) Secondary metabolites from Mexican species of the tribe Senecioneae (Asteraceae). J Mex Chem Soc 51:160–172
Rose EF (1972) Senecio species: toxic plants used as food and medicine in the Transkei. S Afr Med J 46:1039–1043
Roth C, Rastogi S, Arvestad L et al (2007) Evolution after gene duplication: models, mechanisms, sequences, systems, and organisms. J Exp Zool B Mol Dev Evol 308:58–73
Rüeger H, Benn MH (1983) The alkaloids of Senecio triangularis Hook. Can J Chem 61:2526–2529
Sander H, Hartmann T (1989) Site of synthesis, metabolism and translocation of senecionine N-oxide in cultured roots of Senecio erucifolius. Plant Cell Tissue Organ Cult 18:19–32
Schaneberg BT, Molyneux RJ, Khan IA (2004) Evaporative light scattering detection of pyrrolizidine alkaloids. Phytochem Anal 15:36–39
Schmid P, Luethy J, Zweifel U et al (1987) GC/MS characterization of pyrrolizidine alkaloids in some species of Asteraceae. Mitt Lebensm Hyg 78:208–216
Smith LW, Culvenor CCJ (1981) Plant sources of hepatotoxic pyrrolizidine alkaloids. J Nat Prod 44:129–152
Stelljes ME, Kelley RB, Molyneux RJ et al (1991) GC-MS determination of pyrrolizidine alkaloids in four Senecio species. J Nat Prod 54:759–773
Stirling IR, Freer IKA, Robins DJ (1997) Pyrrolizidine alkaloid biosynthesis. Incorporation of 2-aminobutanoic acid labelled with 13C or 2H into the senecic acid portion of rosmarinine and senecionine. J Chem Soc Perkin Trans I 1:677–689
Suau R, Cabezudo B, Rico R et al (2002) Pyrrolizidine alkaloids from three Spanish Senecio species. Biochem Syst Ecol 30:981–984
Susag L, Parvez M, Mathenge S et al (2000) Structure revision of isoline (ruwenine), bisline and isolinecic acid. Phytochemistry 54:933–935
Tan A, Wang Z, He H et al (2003) New pyrrolizidine alkaloids from Ligularia tsangchanensis. Heterocycles 60:1195–1198
Tang J, Akao T, Nakamura N et al (2007) In vitro metabolism of isoline, a pyrrolizidine alkaloid from Ligularia duciformis, by rodent liver microsomal esterase and enhanced hepatotoxicity by esterase inhibitors. Drug Metab Dispos 35:1832–1839
TheArabidopsisGenome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796–815
Thu Huong DT, Martin M-T, Litaudon M et al (1998) Pyrrolizidine alkaloids from Amphorogyne spicata. J Nat Prod 61:1444–1446
Toppel G, Witte L, Riebesehl B et al (1987) Alkaloid patterns and biosynthetic capacity of root cultures from some pyrrolizidine alkaloid producing Senecio species. Plant Cell Rep 6:466–469
Trigo JR, Leal IR, Matzenbacher NI et al (2003) Chemotaxonomic value of pyrrolizidine alkaloids in southern Brazil Senecio (Senecioneae: Asteraceae). Biochem Syst Ecol 31:1011–1022
Tundis R, Loizzo MR, Statti GA et al (2007) Pyrrolizidine alkaloid profiles of the Senecio cineraria group (Asteraceae). Z Naturforsch C: Biosci 62c:467–472
Urones JG, Barcala PB, Marcos IS et al (1988) Pyrrolizidine alkaloids from Senecio gallicus and S. adonidifolius. Phytochemistry 27:1507–1510
Villarroel LH, Varea P, Caceres R (1988) lntergerrimine and usaramine alkaloids from Senecio murorum. Bol Soc Chil Quím 33:107–109
Von Borstel K, Witte L, Hartmann T (1989) Pyrrolizidine alkaloid patterns in populations of Senecio vulgaris, S. vernalis and their hybrids. Phytochemistry 28:1635–1638
Vrieling K, de Vos H, van Wijk CAM (1993) Genetic analysis of the concentrations of pyrrolizidine alkaloids in Senecio jacobaea. Phytochemistry 32:1141–1144
Were O, Benn M, Munavu RM (1991) Pyrrolizidine alkaloids from Senecio hadiensis. J Nat Prod 54:491–499
Were O, Benn M, Munavu RM (1993) The pyrrolizidine alkaloids of Senecio syringifolius and S. hadiensis from Kenya. Phytochemistry 32:1595–1602
Wiedenfeld H, Roeder E (1979) Das Pyrrolizidinalkaloid Senecionin aus Senecio fuchsii. Phytochemistry 18:1083–1084
Wiedenfeld H, Pastewka U, Stengl P et al (1981) Zur gaschromatografischen Bestimmung der Pyrrolizidinalkaloide aus einigen Senecioarten. Pharmazie 41:124–128
Wiedenfeld H, Hendriks H, Bruius AP et al (1989) Zur Alkaloidführung von Senecio nemorensis L. ssp. fuchsii (Gmel.) Celak und Senecio nemorensis L. ssp. nemorensis (Rchb.) Celak. Sci Pharm 57:97–104
Wiedenfeld H, Altanchimeg D, Gantur A et al (2002a) Toxic pyrrolizidine alkaloids from three Mongolian plants. A possible risk for cattle poisoning. J Nat Toxins 11:187–192
Wiedenfeld H, Bourauel T, Roeder E (2002b) Pyrrolizidine Alkaloide in Petasites fragrans. Sci Pharm 70:407–411
Wiedenfeld H, Narantuya S, Dumaa M et al (2003) Pyrrolizidine alkaloids from Ligularia sibirica Cass. and Tephroseris integrifolia L. Sci Pharm 71:129–132
Wiedenfeld H, Montes C, Tawil B et al (2006) Pyrrolizidine alkaloid level in Senecio bicolor (Willd.) Tod, ssp. cineraria (DC.) from Middle Europe. Pharmazie 61:559–561
Witte L, Ehmke A, Hartmann T (1990) Interspecific flow of pyrrolizidine alkaloids; from plants via aphids to ladybirds. Naturwissenschaften 77:540–543
Witte L, Ernst L, Adam H et al (1992a) Chemotypes of two pyrrolizidine alkaloid-containing Senecio species. Phytochemistry 31:559–565
Witte L, Ernst L, Wray V et al (1992b) Revised structure of the main alkaloid of Senecio adonidifolius. Phytochemistry 31:1027–1028
Wrobel JT (1985) Pyrrolizidine alkaloids. In: Brossi A (ed) The alkaloids, vol 26. Academic Press, London, pp 327–384
Yamada K, Tatematsu H, Suziki M et al (1976) Isolation and the structures of two new alkaloids, petasitenine and neopetasitenine from Petasites japonicus Maxim. Chem Lett 5:461–464
Zalkow LH, Asibal CF, Glinski JA et al (2004) Macrocyclic pyrrolizidine alkaloids from Senecio anonymus. Separation of a complex alkaloid extract using droplet counter-current chromatography. J Nat Prod 51:690–702
Zdero C, Bohlmann F, King RM et al (1990) Co-occurrence of pyrrolizidine alkaloids and acylpyrrols in Senecio magnificus and constituents of other australian Senecio species. Phytochemistry 29:509–511
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Parts of the work were supported by the Deutsche Forschungsgemeinschaft (DFG) in grants to D. Ober.
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Langel, D., Ober, D. & Pelser, P.B. The evolution of pyrrolizidine alkaloid biosynthesis and diversity in the Senecioneae. Phytochem Rev 10, 3–74 (2011). https://doi.org/10.1007/s11101-010-9184-y
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DOI: https://doi.org/10.1007/s11101-010-9184-y