Advertisement

Xanthine Alkaloids: Occurrence, Biosynthesis, and Function in Plants

  • Hiroshi AshiharaEmail author
  • Kouichi Mizuno
  • Takao Yokota
  • Alan Crozier
Chapter
Part of the Progress in the Chemistry of Organic Natural Products book series (POGRCHEM, volume 105)

Abstract

Caffeine is a xanthine alkaloid found in non-alcoholic beverages such as tea, coffee, and cocoa. It was discovered in tea and coffee in the 1820s, but it was not until 2000 that details of molecular events associated with caffeine biosynthesis began to be unraveled. Reviewed are the occurrence of xanthine alkaloids in the plant kingdom and the elucidation of the caffeine biosynthesis pathway, providing details of the N-methyltransferases, belonging to the motif B′ methyltransferase family, which catalyze three steps in the four-step pathway leading from xanthosine to caffeine. Pathways for the metabolism and degradation of xanthine alkaloids are discussed, although as yet the genes and enzymes involved have not been isolated. This chapter also considers the in planta role of caffeine in chemical defense that has been demonstrated using transgenic caffeine-forming tobacco and chrysanthemum plants, which are resistant to attack by pathogens and herbivores. Finally, future research is considered that might lead to the production of naturally decaffeinated beverages and agricultural crops that contain elevated levels of “natural” pesticides.

Keywords

Camellia sinensis Coffea spp Theobroma cacao Methylxanthines Caffeine Occurrence Biosynthesis Catabolism Transgenics Function 

Notes

Acknowledgements

We would like to thank Professor Andrew A. McCarthy, European Molecular Biology Laboratory, Grenoble, France for providing a personal communication on the current status of 7-methylxanthosine synthase. The authors also thank Professor Tatsuhito Fujimura, University of Tsukuba, Japan for drawing Fig. 2.

References

  1. 1.
    Ashihara H, Crozier A (2001) Caffeine: a well known but little mentioned compound in plant science. Trends Plant Sci 6:407CrossRefGoogle Scholar
  2. 2.
    Runge FF (1820) Neueste phytochemische Entdeckungen zur Begründung einer wissenschaftlichen Phytochemie. In: Phytochemische Entdeckungen. Reimer, Berlin, p 204Google Scholar
  3. 3.
    Von Giese F (1820) Vermischte Notizen. 1. Kaffeestoff und Salzgehalt des Quassia Extrakts. Ann Chem 4:240Google Scholar
  4. 4.
    Oudry V (1927) Thein, eine organische Salzbase im Thee (Thea chinesis). Mag Pharm 19:49Google Scholar
  5. 5.
    Stenhouse J (1843) Über Thein und seine Darstellung. Liebigs Ann Chem 45:366CrossRefGoogle Scholar
  6. 6.
    Daniell WF (1865) On the kola-nut of tropical West Africa (the guru nut of Soudan). Pharm J 6:450Google Scholar
  7. 7.
    Woskresensky A (1842) Über das Theobromin. Liebigs Ann Chem 41:125CrossRefGoogle Scholar
  8. 8.
    Salomon G. Über Paraxanthin und Heteroxanthin. Ber Dtsch Chem Ges 18:3406Google Scholar
  9. 9.
    Chou CH, Waller GR (1980) Possible allelopathic constituents of Coffea arabica. J Chem Ecol 6:643CrossRefGoogle Scholar
  10. 10.
    Fischer E, Ach L (1895) Synthese des Caffeins. Ber Dtsch Chem Ges 28:3135CrossRefGoogle Scholar
  11. 11.
    Kato M, Mizuno K, Fujimura T, Iwama M, Irie M, Crozier A, Ashihara H (1999) Purification and characterization of caffeine synthase from tea leaves. Plant Physiol 120:579CrossRefGoogle Scholar
  12. 12.
    Kato M, Mizuno K, Crozier A, Fujimura T, Ashihara H (2000) A gene encoding caffeine synthase from tea leaves. Nature 406:956CrossRefGoogle Scholar
  13. 13.
    Ashihara H, Crozier A (1999) Biosynthesis and metabolism of caffeine and related purine alkaloids in plants. Adv Bot Res 30:117CrossRefGoogle Scholar
  14. 14.
    Sano H, Kim Y-S, Choi Y-E (2013) Like cures like: caffeine immunizes plants against biotic stresses. Adv Bot Res 68:273Google Scholar
  15. 15.
    Tarka SM, Hurst WJ (1998) Introduction to the chemistry, isolation, and biosynthesis of methylxanthines. In: Spiller GA (ed) Caffeine. CRC Press, Boca Raton, FL, p 1Google Scholar
  16. 16.
    Kihlman BA (1977) Occurrence and biosynthesis of methylated oxypurines in plants. In: Caffeine and chromosome. Elsevier, Amsterdam, p 11Google Scholar
  17. 17.
    Willaman JJ, Schubert BG (1961) Alkaloid-bearing plants and their contained alkaloids, Technical Bulletin No. 1234. Agricultural Research Service, U.S. Department of Agriculture, Washington, DCGoogle Scholar
  18. 18.
    O’Connell FD (1969) Isolation of caffeine from Banisteriopsis inebrians (Malpighiaceae). Naturwissenschaften 56:139CrossRefGoogle Scholar
  19. 19.
    Stewart I (1985) Identification of caffeine in citrus flowers and leaves. J Agric Food Chem 33:1163CrossRefGoogle Scholar
  20. 20.
    Kretschmar JA, Baumann TW (1999) Caffeine in Citrus flowers. Phytochemistry 52:19CrossRefGoogle Scholar
  21. 21.
    Smith AR, Pryer KM, Schuettpelz E, Korall P, Schneider H, Wolf PG (2006) A classification for extant ferns. Taxon 55:705CrossRefGoogle Scholar
  22. 22.
    The Angiosperm Phylogeny Group (2009) An update of the angiosperm phylogeny group classification for the orders and families of flowering plants: APG III. Bot J Linn Soc 161:105CrossRefGoogle Scholar
  23. 23.
    Nagata T, Sakai S (1984) Differences in caffeine, flavonols and amino acids contents in leaves of cultivated species of Camellia. Jpn J Breed 34:459CrossRefGoogle Scholar
  24. 24.
    Nagata T, Sakai S (1985) Caffeine, flavanol and amino acid contents in leaves of hybrids and species of the section Dubiae in the genus Camellia. Jpn J Breed 35:1CrossRefGoogle Scholar
  25. 25.
    Nagata T, Sakai S (1985) Purine base pattern of Camellia irrawadiensis. Phytochemistry 24:2271CrossRefGoogle Scholar
  26. 26.
    Ye CX, Lin Y, Zhou H, Cheng F, Li X (1997) Isolation and analysis of purine alkaloids from Camellia ptilophylla Chang. Acta Scientiarum Naturalium Universitatis Sunyatseni 36:30Google Scholar
  27. 27.
    Johnson TB (1937) Purines in the plant kingdom: the discovery of a new purine in tea. J Am Chem Soc 59:1261CrossRefGoogle Scholar
  28. 28.
    Ye C, Lin Y, Su J, Zhang H (1999) Purine alkaloids in Camellia assamica var. kucha Chang et Wang. Acta Scientiarum Naturalium Universitatis Sunyatseni 38:82Google Scholar
  29. 29.
    Zheng XQ, Ye CX, Kato M, Crozier A, Ashihara H (2002) Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha). Phytochemistry 60:129CrossRefGoogle Scholar
  30. 30.
    Deng W-W (2011) Biosynthesis of secondary metabolites in tea plants. PhD thesis, Ochanomizu University, TokyoGoogle Scholar
  31. 31.
    Ishida M, Kitao N, Mizuno K, Tanikawa N, Kato M (2009) Occurrence of theobromine synthase genes in purine alkaloid-free species of Camellia plants. Planta 229:559CrossRefGoogle Scholar
  32. 32.
    Deng W-W, Jin Y, Yuan Y, Zhang Z-Z (2013) Profile of purine metabolism and purine alkaloid biosynthesis in Schima and Eurya plants. Bull Bot Res 33:410Google Scholar
  33. 33.
    Ashihara H, Kubota H (1986) Patterns of adenine metabolism and caffeine biosynthesis in different parts of tea seedlings. Physiol Plant 68:275CrossRefGoogle Scholar
  34. 34.
    van Breda SV, Merwe CF, Robbertse H, Apostolides Z (2013) Immunohistochemical localization of caffeine in young Camellia sinensis (L.) O. Kuntze (tea) leaves. Planta 237:849CrossRefGoogle Scholar
  35. 35.
    Petracco M (2005) Our everyday cup of coffee: the chemistry behind its magic. J Chem Educ 82:1161CrossRefGoogle Scholar
  36. 36.
    Mazzafera P, Carvalho A (1992) Breeding for low seed caffeine content of coffee (Coffea L.) by interspecific hybridization. Euphytica 59:55Google Scholar
  37. 37.
    Anthony F, Clifford MN, Noirot M (1993) Biochemical diversity in the genus Coffea L.: chlorogenic acids, caffeine and mozambioside contents. Genet Resour Crop Evol 40:61Google Scholar
  38. 38.
    Silvarolla MB, Mazzafera P, Fazuoli LC (2004) Plant biochemistry: a naturally decaffeinated arabica coffee. Nature 429:826CrossRefGoogle Scholar
  39. 39.
    Baumann TW, Oechslin M, Wanner H (1976) Caffeine and methylated uric acids: chemical patterns during vegetative development of Coffea liberica. Biochem Physiol Pflanzen 170:217Google Scholar
  40. 40.
    Petermann J, Baumann TW (1983) Metabolic relations between methylxanthines and methyluric acids in Coffea. Plant Physiol 73:961CrossRefGoogle Scholar
  41. 41.
    Zheng XQ, Ashihara H (2004) Distribution, biosynthesis and function of purine and pyridine alkaloids in Coffea arabica seedlings. Plant Sci 166:807CrossRefGoogle Scholar
  42. 42.
    Frischknecht PM, Ulmer-Dufek J, Baumann TW (1986) Purine alkaloid formation in buds and developing leaflets of Coffea arabica: expression of an optimal defence strategy? Phytochemistry 25:613CrossRefGoogle Scholar
  43. 43.
    Fujimori N, Ashihara H (1994) Biosynthesis of theobromine and caffeine in developing leaves of Coffea arabica. Phytochemistry 36:1359CrossRefGoogle Scholar
  44. 44.
    Keller H, Wanner H, Baumann TW (1972) Kaffeinsynthese in Fruchten und Gewebekulturen von Coffea arabica. Planta 108:339CrossRefGoogle Scholar
  45. 45.
    Koshiro Y, Zheng XQ, Wang M, Nagai C, Ashihara H (2006) Changes in content and biosynthetic activity of caffeine and trigonelline during growth and ripening of Coffea arabica and Coffea canephora fruits. Plant Sci 171:242CrossRefGoogle Scholar
  46. 46.
    Clifford MN, Ramirez-Martinez JR (1990) Chlorogenic acids and purine alkaloids contents of maté (Ilex paraguariensis) leaf and beverage. Food Chem 35:13CrossRefGoogle Scholar
  47. 47.
    Alikaridis F (1987) Natural constituents of Ilex species. J Ethnopharmacol 20:121CrossRefGoogle Scholar
  48. 48.
    Filip R, de Iglesias DIA, Rondina RVD, Coussio JD (1983) Análisis de las hojas y tallos de Ilex argentina Lillo. I. Xantinas. Acta Farm Bonaerense 2:87Google Scholar
  49. 49.
    Edwards AL, Bennett BC (2005) Diversity of methylxanthine content in Ilex cassine L. and Ilex vomitoria Ait.: assessing sources of the North American stimulant cassina. Econ Bot 59:275CrossRefGoogle Scholar
  50. 50.
    Mazzafera P (1994) Caffeine, theobromine and theophylline distribution in Ilex paraguariensis. Rev Brasil Fisiol Veg 6:149Google Scholar
  51. 51.
    Crozier A, Ashihara H, Tomas-Barberan F (eds) (2012) Teas, cocoa and coffee: plant secondary metabolites and health. Wiley-Blackwell, Oxford, UKGoogle Scholar
  52. 52.
    Pereira-Caro G, Borges G, Nagai C, Jackson MC, Yokota T, Crozier A, Ashihara H (2013) Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario. J Agric Food Chem 61:427CrossRefGoogle Scholar
  53. 53.
    Timbie DJ, Sechrist L, Keeney PG (1978) Application of high-pressure liquid chromatography to the study of variables affecting theobromine and caffeine concentrations in cocoa beans. J Food Sci 43:560CrossRefGoogle Scholar
  54. 54.
    Hammerstone JF Jr, Romanczyk LJ Jr, Aitkent WM (1994) Purine alkaloid distribution within Herrania and Theobroma. Phytochemistry 35:1237CrossRefGoogle Scholar
  55. 55.
    Kufer J, McNeil CL (2009) The jaguar tree (Theobroma bicolor Bonpl.). In: McNeil CL (ed) Chocolate in Mesoamerica: a cultural history of cacao. Oxford University Press, Oxford, UK, p 542Google Scholar
  56. 56.
    Koyama Y, Tomoda Y, Kato M, Ashihara H (2003) Metabolism of purine bases, nucleosides and alkaloids in theobromine-forming Theobroma cacao leaves. Plant Physiol Biochem 41:977CrossRefGoogle Scholar
  57. 57.
    Gurney KA, Evans LV, Robinson DS (1991) Extraction of purine alkaloids from cocoa tissues and determination by high-performance liquid chromatography. Phytochem Anal 2:15CrossRefGoogle Scholar
  58. 58.
    Senanayake UM, Wijesekera ROB (1971) Theobromine and caffeine content of the cocoa bean during its growth. J Sci Food Agric 22:262CrossRefGoogle Scholar
  59. 59.
    Sotelo A, Alvarez RG (1991) Chemical composition of wild-Theobroma species and their comparison to the cacao bean. J Agric Food Chem 39:1940CrossRefGoogle Scholar
  60. 60.
    Bucheli P, Rousseau G, Alvarez M, Laloi M, McCarthy J (2001) Developmental variation of sugars, carboxylic acids, purine alkaloids, fatty acids, and endoproteinase activity during maturation of Theobroma cacao L. seeds. J Agric Food Chem 49:5046CrossRefGoogle Scholar
  61. 61.
    Zheng X-Q, Koyama Y, Nagai C, Ashihara H (2004) Biosynthesis, accumulation and degradation of theobromine in developing Theobroma cacao fruits. J Plant Physiol 161:363CrossRefGoogle Scholar
  62. 62.
    Belliardo F, Martelli A, Valle M (1985) HPLC determination of caffeine and theophylline in Paullinia cupana Kunth (Guarana) and Cola spp. samples. Z Lebensm Unters Forsch 180:398Google Scholar
  63. 63.
    Niemenak N, Onomo PE, Fotso, Lieberei R, Ndoumou DO (2008) Purine alkaloids and phenolic compounds in three Cola species and Garcinia kola grown in Cameroon. S Afr J Bot 74:629CrossRefGoogle Scholar
  64. 64.
    Schimpl FC, Kiyota E, Mayer JLS, Gonçalves JFdC, da Silva JF, Mazzafera P (2014) Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit. Phytochemistry 105:25Google Scholar
  65. 65.
    Weckerle CS, Stutz MA, Baumann TW (2003) Purine alkaloids in Paullinia. Phytochemistry 64:735CrossRefGoogle Scholar
  66. 66.
    Baumann TW, Schulthess BH, Hanni K (1995) Guarana (Paullinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 39:1063CrossRefGoogle Scholar
  67. 67.
    Ashihara H, Yokota T, Crozier A (2013) Biosynthesis and catabolism of purine alkaloids. Adv Bot Res 68:111CrossRefGoogle Scholar
  68. 68.
    Pierattini E, Francini A, Raffaelli A, Sebastiani L (2016) Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism. Environ Sci Pollut Res 23:7289CrossRefGoogle Scholar
  69. 69.
    Ashihara H, Ludwig IA, Katahira R, Yokota T, Fujimura T, Crozier A (2014) Trigonelline and related nicotinic acid metabolites: occurrence, biosynthesis, taxonomic considerations, and their roles in planta and in human health. Phytochem Rev 14:765CrossRefGoogle Scholar
  70. 70.
    Bruton T, Alboloushi A, Garza Bdl, Kim BO, Halden RU (2010) Fate of caffeine in the environment and ecotoxicological considerations. In: Contaminants of emerging concern in the environment: ecological and human health considerations, ACS Symposium Series, vol 1048. American Chemical Society, Washington DC, p 257Google Scholar
  71. 71.
    Bonner J (1950) Plant biochemistry. Academic Press, New YorkGoogle Scholar
  72. 72.
    Bresler HW (1904) Uber die Bestimmung der Nucleinbasen im Safte von Beta vulgaris. Hoppe Seyler’s Z Physiol Chem 4:535CrossRefGoogle Scholar
  73. 73.
    Weevers T (1930) Die Funkion der Xanthinderivate im Pflanzenstoffwechsel. Arch Neerl Sci 3B(5):111Google Scholar
  74. 74.
    Anderson L, Gibbs M (1962) The biosynthesis of caffeine in the coffee plant. J Biol Chem 237:1941Google Scholar
  75. 75.
    Inoue T, Yamashita S, Kawamura Y, Sasaki G (1960) Studies on biogenesis of tea components. I. Absorption of 15N to new leaves and old leaves. Yakugaku Zasshi 80:548Google Scholar
  76. 76.
    Inoue T, Kawamura Y (1961) Studies on biogenesis of tea components. II. Formation of caffeine in excised tea shoots. Chem Pharm Bull 9:236Google Scholar
  77. 77.
    Inoue T (1972) Studies on biogenesis of tea components. IV. Incorporation of glycine-2-14C to caffeine. Proc Hoshi Coll Pharm (Tokyo) 13:60Google Scholar
  78. 78.
    Inoue T, Adachi F (1962) Studies on biogenesis of tea components. III. The origin of the methyl groups in caffeine. Chem. Pharm Bull 10:1212CrossRefGoogle Scholar
  79. 79.
    Serenkov GP, Proiser E (1961) Biosynthesis of caffeine in tea leaves. Dokl Akad Nauk USSR 140:716Google Scholar
  80. 80.
    Proiser E, Serenkov GP (1963) Caffeine biosynthesis in tea leaves. Biokhimiya (Moscow) 28:857Google Scholar
  81. 81.
    Konishi S, Ozawa M, Takahashi E (1972) Metabolic conversion of N-methyl carbon of γ-glutamylmethylamide to caffeine in tea plants. Plant Cell Physiol 13:365Google Scholar
  82. 82.
    Konishi S, Inoue T, Takahashi E (1972) Localization of the carbon in caffeine biosynthesized from N-methyl carbon of γ-glutamylmethylamide in tea plants. Plant Cell Physiol 13:695Google Scholar
  83. 83.
    Suzuki T (1972) The participation of S-adenosylmethionine in the biosynthesis of caffeine in the tea plant. FEBS Lett 24:18CrossRefGoogle Scholar
  84. 84.
    Suzuki T (1973) Metabolism of methylamine in the tea plant (Thea sinensis L.). Biochem J 132:753CrossRefGoogle Scholar
  85. 85.
    Suzuki T, Takahashi E (1975) Metabolism of xanthine and hypoxanthine in the tea plant (Thea sinensis L.). Biochem J 146:79CrossRefGoogle Scholar
  86. 86.
    Suzuki T, Takahashi E (1976) Caffeine biosynthesis in Camellia sinensis. Phytochemistry 15:1235CrossRefGoogle Scholar
  87. 87.
    Looser E, Baumann TW, Wanner H (1974) The biosynthesis of caffeine in the coffee plant. Phytochemistry 13:2515CrossRefGoogle Scholar
  88. 88.
    Ogutuga DBA, Northcote DH (1970) Caffeine formation in tea callus tissue. J Exp Bot 21:258CrossRefGoogle Scholar
  89. 89.
    Ogutuga DBA, Northcote DH (1970) Biosynthesis of caffeine in tea callus tissue. Biochem J 117:715CrossRefGoogle Scholar
  90. 90.
    Keller H, Wanner H, Baumann TW (1972) Kaffeinsynthese in Früchten und Gewebekulturen von Coffea arabica. Planta 108:339CrossRefGoogle Scholar
  91. 91.
    Suzuki T, Takahashi E (1976) Metabolism of methionine and biosynthesis of caffeine in the tea plant (Camellia sinensis L.). Biochem J 160:171CrossRefGoogle Scholar
  92. 92.
    Suzuki T, Takahashi E (1976) Further investigation of the biosynthesis of caffeine in tea plants (Camellia sinensis L.): methylation of transfer ribonucleic acid by tea leaf extracts. Biochem J 160:181CrossRefGoogle Scholar
  93. 93.
    Loomis WD (1969) Removal of phenolic compounds during the isolation of plant enzymes. In: Methods in enzymology, vol 13. Academic Press, New York, p 555Google Scholar
  94. 94.
    Suzuki T, Takahashi E (1975) Biosynthesis of caffeine by tea-leaf extracts: enzymic formation of theobromine from 7-methylxanthine and of caffeine from theobromine. Biochem J 146:87CrossRefGoogle Scholar
  95. 95.
    Roberts MF, Waller GR (1979) N-Methyltransferases and 7-methyl-N9-nucleoside hydrolase activity in Coffea arabica and the biosynthesis of caffeine. Phytochemistry 18:451CrossRefGoogle Scholar
  96. 96.
    Baumann TW, Koetz R, Morath P (1983) N-Methyltransferase activities in suspension cultures of Coffea arabica L. Plant Cell Rep 2:33Google Scholar
  97. 97.
    Waller GR, MacVean CD, Suzuki T (1983) High production of caffeine and related enzyme activities in callus cultures of Coffea arabica L. Plant Cell Rep 2:109CrossRefGoogle Scholar
  98. 98.
    Negishi O, Ozawa T, Imagawa H (1985) Methylation of xanthosine by tea-leaf extracts and caffeine biosynthesis. Agric Biol Chem 49:887Google Scholar
  99. 99.
    Negishi O, Ozawa T, Imagawa H (1988) N-Methylnucleosidase from tea leaves. Agric Biol Chem 52:169Google Scholar
  100. 100.
    Ashihara H, Nobusawa E (1981) Metabolic fate of [8-14C]adenine and [8-14C]hypoxanthine in higher plants. Z Pflanzenphysiol 104:443CrossRefGoogle Scholar
  101. 101.
    Nobusawa E, Ashihara H (1983) Purine metabolism in cotyledons and embryonic axes of black gram (Phaseolus mungo L.) seedlings. Int J Biochem 15:1059CrossRefGoogle Scholar
  102. 102.
    Ashihara H, Kubota H (1987) Biosynthesis of purine alkaloids in Camellia plants. Plant Cell Physiol 28:535Google Scholar
  103. 103.
    Ashihara H (1993) Purine metabolism and the biosynthesis of caffeine in maté leaves. Phytochemistry 33:1427CrossRefGoogle Scholar
  104. 104.
    Negishi O, Ozawa T, Imagawa H (1992) Biosynthesis of caffeine from purine nucleotides in tea plant. Biosci Biotechnol Biochem 56:499CrossRefGoogle Scholar
  105. 105.
    Suzuki T, Ashihara H, Waller GR (1992) Purine and purine alkaloid metabolism in Camellia and Coffea plants. Phytochemistry 31:2575CrossRefGoogle Scholar
  106. 106.
    Koshiishi C, Kato A, Yama S, Crozier A, Ashihara H (2001) A new caffeine biosynthetic pathway in tea leaves: utilisation of adenosine released from the S-adenosyl-l-methionine cycle. FEBS Lett 499:50Google Scholar
  107. 107.
    Nazario GM, Lovatt CJ (1993) Separate de novo and salvage purine pools are involved in the biosynthesis of theobromine but not caffeine in leaves of Coffea arabica L. Plant Physiol 103:1203CrossRefGoogle Scholar
  108. 108.
    Ashihara H, Monteiro AM, Gillies FM, Crozier A (1996) Biosynthesis of caffeine in leaves of coffee. Plant Physiol 111:747CrossRefGoogle Scholar
  109. 109.
    Schulthess BH, Morath P, Baumann TW (1996) Caffeine biosynthesis starts with the metabolically channelled formation of 7-methyl-XMP. A new hypothesis. Phytochemistry 41:169CrossRefGoogle Scholar
  110. 110.
    Schulthess BH, Baumann TW (1995) Are xanthosine and 7-methylxanthosine caffeine precursors? Phytochemistry 39:1363CrossRefGoogle Scholar
  111. 111.
    Mizuno K, Kato M, Irino F, Yoneyama N, Fujimura T, Ashihara H (2003) The first committed step reaction of caffeine biosynthesis: 7-methylxanthosine synthase is closely homologous to caffeine synthases in coffee (Coffea arabica L.). FEBS Lett 547:56Google Scholar
  112. 112.
    Gillies FM, Jenkins GI, Ashihara H, Crozier A (1995) In vitro-biosynthesis of caffeine: the stability of N-methyltransferase activity in cell-free preparations from liquid endosperm of Coffea arabica. In: Proceedings of the 16th international conference on coffee science, ASIC, Paris, p 599Google Scholar
  113. 113.
    Mazzafera P, Wingsle G, Olsson O, Sandberg G (1994) S-Adenosyl-l-methionine:theobromine 1-N-methyltransferase, an enzyme catalysing the synthesis of caffeine in coffee. Phytochemistry 17:1577Google Scholar
  114. 114.
    Ashihara H, Kato M, Crozier A (1996) Caffeine biosynthesis in leaves of Camellia sinensis: substrate specificity of N-methyltransferase. In: Principles regulating biosynthesis and storage of secondary products. Phytochemical Society of Europe, Halle-Wittenberg, p 40Google Scholar
  115. 115.
    Kato M, Kanehara T, Shimizu H, Suzuki T, Gillies FM, Crozier A, Ashihara H (1996) Caffeine biosynthesis in young leaves of Camellia sinensis: in vitro studies on N-methyltransferase activity involved in the conversion of xanthosine to caffeine. Physiol Plant 98:629CrossRefGoogle Scholar
  116. 116.
    Mosli Waldhauser SS, Gillies FM, Crozier A, Baumann TW (1997) Separation of the N-7 methyltransferase, the key enzyme in caffeine biosynthesis. Phytochemistry 45:1407CrossRefGoogle Scholar
  117. 117.
    Kato M, Mizuno K, Crozier A, Fujimura T, Ashihara H (2000) Plant biotechnology: caffeine synthase gene from tea leaves. Nature 406:956CrossRefGoogle Scholar
  118. 118.
    Moisyadi S, Neupane KR, Stiles JI (1998) Cloning and characterization of a cDNA encoding xanthosine-N7-methyltransferase from coffee (Coffea arabica). Acta Hort 461:367CrossRefGoogle Scholar
  119. 119.
    Moisyadi S, Neupane KR, Stiles JI (1999) Cloning and characterization of xanthosine-N7-methyltransferase, the first enzyme of the caffeine biosynthetic pathway. In: Proceedings of 18th international conference on coffee science, ASIC, Paris, p 327Google Scholar
  120. 120.
    Uefuji H, Tatsumi Y, Morimoto M, Kaothien-Nakayama P, Ogita S, Sano H (2005) Caffeine production in tobacco plants by simultaneous expression of three coffee N-methyltransferases and its potential as a pest repellent. Plant Mol Biol 59:221CrossRefGoogle Scholar
  121. 121.
    Mizuno K, Okuda A, Kato M, Yoneyama N, Tanaka H, Ashihara H, Fujimura T (2003) Isolation of a new dual-functional caffeine synthase gene encoding an enzyme for the conversion of 7-methylxanthine to caffeine from coffee (Coffea arabica L.). FEBS Lett 534:75CrossRefGoogle Scholar
  122. 122.
    Mizuno K, Tanaka H, Kato M, Ashihara H, Fujimura T (2001) cDNA cloning of caffeine (theobromine) synthase from coffee (Coffea arabica L.). In: Proceedings of 18th international conference on coffee science, ASIC, Paris, p 815Google Scholar
  123. 123.
    Ogawa M, Herai Y, Koizumi N, Kusano T, Sano H (2001) 7-Methylxanthine methyltransferase of coffee plants. Gene isolation and enzymatic properties. J Biol Chem 276:8213CrossRefGoogle Scholar
  124. 124.
    Uefuji H, Ogita S, Yamaguchi Y, Koizumi N, Sano H (2003) Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants. Plant Physiol 132:372CrossRefGoogle Scholar
  125. 125.
    Ashihara H, Sano H, Crozier A (2008) Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69:841CrossRefGoogle Scholar
  126. 126.
    Negishi O, Ozawa T, Imagawa H (1985) Conversion of xanthosine into caffeine in tea plants. Agric Biol Chem 49:251Google Scholar
  127. 127.
    Yue Y, Guo H (2014) Quantum mechanical/molecular mechanical study of catalytic mechanism and role of key residues in methylation reactions catalyzed by dimethylxanthine methyltransferase in caffeine biosynthesis. J Chem Inf Model 54:593CrossRefGoogle Scholar
  128. 128.
    Fujimori N, Suzuki T, Ashihara H (1991) Seasonal variations in biosynthetic capacity for the synthesis of caffeine in tea leaves. Phytochemistry 30:2245CrossRefGoogle Scholar
  129. 129.
    McCarthy AA, McCarthy JG (2007) The structure of two N-methyltransferases from the caffeine biosynthetic pathway. Plant Physiol 144:879CrossRefGoogle Scholar
  130. 130.
    Ashihara H, Gillies FM, Crozier A (1997) Metabolism of caffeine and related purine alkaloids in leaves of tea (Camellia sinensis L.). Plant Cell Physiol 38:413Google Scholar
  131. 131.
    Yoneyama N, Morimoto H, Ye CX, Ashihara H, Mizuno K, Kato M (2006) Substrate specificity of N-methyltransferase involved in purine alkaloids synthesis is dependent upon one amino acid residue of the enzyme. Mol Genet Genomics 275:125CrossRefGoogle Scholar
  132. 132.
    Kato M, Mizuno K (2004) Caffeine synthase and related methyltransferases in plants. Front Biosci 9:1833CrossRefGoogle Scholar
  133. 133.
    Joshi CP, Chiang VL (1998) Conserved sequence motifs in plant S-adenosyl-l-methionine-dependent methyltransferases. Plant Mol Biol 37:663CrossRefGoogle Scholar
  134. 134.
    Ross JR, Nam KH, D’Auria JC, Pichersky E (1999) S-Adenosyl-methionine:salicylic acid carboxyl methyltransferase, an enzyme involved in floral scent production and plant defense, represents a new class of plant methyltransferases. Arch Biochem Biophys 367:9CrossRefGoogle Scholar
  135. 135.
    Dudareva N, Murfitt LM, Mann CJ, Gorenstein N, Kolosova N, Kish CM, Bonham C, Wood K (2000) Developmental regulation of methyl benzoate biosynthesis and emission in snapdragon flowers. Plant Cell 12:949CrossRefGoogle Scholar
  136. 136.
    Seo HS, Song JT, Cheong JJ, Lee YH, Lee YW, Hwang I, Lee JS, Choi YD (2001) Jasmonic acid carboxyl methyltransferase: a key enzyme for jasmonate-regulated plant responses. Proc Natl Acad Sci USA 98:4788CrossRefGoogle Scholar
  137. 137.
    Yang Y, Yuan JS, Ross J, Noel JP, Pichersky E, Chen F (2006) An Arabidopsis thaliana methyltransferase capable of methylating farnesoic acid. Arch Biochem Biophys 448:123CrossRefGoogle Scholar
  138. 138.
    Zhao N, Ferrer J-L, Ross J, Guan J, Yang Y, Pichersky E, Noel JP, Chen F (2008) Structural, biochemical, and phylogenetic analyses suggest that indole-3-acetic acid methyltransferase is an evolutionarily ancient member of the SABATH family. Plant Physiol 146:455CrossRefGoogle Scholar
  139. 139.
    Varbanova M, Yamaguchi S, Yang Y, McKelvey K, Hanada A, Borochov R, Yu F, Jikumaru Y, Ross J, Cortes D, Ma CJ, Noel JP, Mander L, Shulaev V, Kamiya Y, Rodermel S, Weiss D, Pichersky E (2007) Methylation of gibberellins by Arabidopsis GAMT1 and GAMT2. Plant Cell 19:32CrossRefGoogle Scholar
  140. 140.
    Murata J, Roepke J, Gordon H, De Luca V (2008) The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell 20:524CrossRefGoogle Scholar
  141. 141.
    D’Auria JC, Chen F, Pichersky E (2003) The SABATH family of MTS in Arabidopsis thaliana and other plant species. In: John TR (ed) Recent advances in phytochemistry, vol 37. Elsevier, Oxford, UK, p 253Google Scholar
  142. 142.
    Zubieta C, Ross JR, Koscheski P, Yang Y, Pichersky E, Noel JP (2003) Structural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family. Plant Cell 15:1704CrossRefGoogle Scholar
  143. 143.
    Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R, Pietrella M, Zheng C, Alberti A, Anthony F, Aprea G, Aury J-M, Bento P, Bernard M, Bocs S, Campa C, Cenci A, Combes M-C, Crouzillat D, Da Silva C, Daddiego L, De Bellis F, Dussert S, Garsmeur O, Gayraud T, Guignon V, Jahn K, Jamilloux V, Joët T, Labadie K, Lan T, Leclercq J, Lepelley M, Leroy T, Li L-T, Librado P, Lopez L, Muñoz A, Noel B, Pallavicini A, Perrotta G, Poncet V, Pot D, Priyono, Rigoreau M, Rouard M, Rozas J, Tranchant-Dubreuil C, VanBuren R, Zhang Q, Andrade AC, Argout X, Bertrand B, de Kochko A, Graziosi G, Henry RJ, Jayarama MR, Nagai C, Rounsley S, Sankoff D, Giuliano G, Albert VA, Wincker P, Lashermes P (2014) The coffee genome provides insight into the convergent evolution of caffeine biosynthesis. Science 345:1181CrossRefGoogle Scholar
  144. 144.
    Pichersky E, Lewinsohn E (2011) Convergent evolution in plant specialized metabolism. Annu Rev Plant Biol 62:549CrossRefGoogle Scholar
  145. 145.
    Perrois C, Strickler S, Mathieu G, Lepelley M, Bedon L, Michaux S, Husson J, Mueller L, Privat I (2015) Differential regulation of caffeine metabolism in Coffea arabica (Arabica) and Coffea canephora (Robusta). Planta 241:179CrossRefGoogle Scholar
  146. 146.
    Mizuno K, Matsuzaki M, Kanazawa S, Tokiwano T, Yoshizawa Y, Kato M (2014) Conversion of nicotinic acid to trigonelline is catalyzed by N-methyltransferase belonged to motif B′ methyltransferase family in Coffea arabica. Biochem Biophys Res Commun 452:1060CrossRefGoogle Scholar
  147. 147.
    Ashihara H, Ludwig I, Katahira R, Yokota T, Fujimura T, Crozier A (2015) Trigonelline and related nicotinic acid metabolites: occurrence, biosynthesis, taxonomic considerations, and their roles in planta and in human health. Phytochem Rev 14:765CrossRefGoogle Scholar
  148. 148.
    Ashihara H (2015) Plant biochemistry: trigonelline biosynthesis in Coffea arabica and Coffea canephora. In: Preedy VR (ed) Coffee in health and disease prevention. Academic Press, San Diego, p 19CrossRefGoogle Scholar
  149. 149.
    Arabidopsis-Genome-Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796CrossRefGoogle Scholar
  150. 150.
    International-Rice-Genome-Sequencing-Project (2005) The map-based sequence of the rice genome. Nature 436:793CrossRefGoogle Scholar
  151. 151.
    Zrenner R, Ashihara H (2011) Nucleotide metabolism. In: Ashihara H, Crozier A, Komamine A (eds) Plant metabolism and biotechnology. Wiley, Chichester, UK, p 135CrossRefGoogle Scholar
  152. 152.
    Ito E, Ashihara H (1999) Contribution of purine nucleotide biosynthesis de novo to the formation of caffeine in young tea (Camellia sinensis) leaves. J Plant Physiol 254:145CrossRefGoogle Scholar
  153. 153.
    Yabuki N, Ashihara H (1991) Catabolism of adenine nucleotides in suspension-cultured plant cells. Biochim Biophys Acta 1073:474CrossRefGoogle Scholar
  154. 154.
    Fujimori N, Ashihara H (1993) Biosynthesis of caffeine in flower buds of Camellia sinensis. Ann Bot 71:279CrossRefGoogle Scholar
  155. 155.
    Baumann TW (2015) Revisiting caffeine biosynthesis — speculations about the proximate source of its purine ring. Nat Prod Commun 10:793Google Scholar
  156. 156.
    Kremers RE (1954) Speculation on DPN as a biochemical precursor of caffeine and trigonelline in coffee. J Am Pharm Assoc 43:423CrossRefGoogle Scholar
  157. 157.
    Negishi O, Ozawa T, Imagawa H (1994) Guanosine deaminase and guanine deaminase from tea leaves. Biosci Biotechnol Biochem 58:1277CrossRefGoogle Scholar
  158. 158.
    Ashihara H, Takasawa Y, Suzuki T (1997) Metabolic fate of guanosine in higher plants. Physiol Plant 100:909CrossRefGoogle Scholar
  159. 159.
    Mager J, Magasanik B (1960) Guanosine-5′-phosphate reductase and its role in the interconversion of purine nucleotides. J Biol Chem 235:1474Google Scholar
  160. 160.
    Stephens RW, Whittaker VK (1973) Calf thymus GMP reductase: control by XMP. Biochem Biophys Res Commun 53:975CrossRefGoogle Scholar
  161. 161.
    Renart MF, Sillero A (1974) GMP reductase in Artemia salina. Biochim Biophys Acta 341:178CrossRefGoogle Scholar
  162. 162.
    Le Floc’h F, Lafleuriel J, Guillot A (1982) Interconversion of purine nucleotides in Jerusalem artichoke shoots. Plant Sci Lett 27:309CrossRefGoogle Scholar
  163. 163.
    Ashihara H, Mitsui K, Yabuki N, Nygaard P (1991) Adenosine metabolism and growth of adenosine-requiring mutant cells of Datura innoxia. Int J Purine Pyrimidine Res 2:129Google Scholar
  164. 164.
    Shoji T, Hashimoto T (2011) Nicotine biosynthesis. In: Ashihara H, Crozier A, Komamine A (eds) Plant metabolism and biotechnology. Wiley, Chichester UK, p 191CrossRefGoogle Scholar
  165. 165.
    Yazaki K, Sugiyama A, Morita M, Shitan N (2008) Secondary transport as an efficient membrane transport mechanism for plant secondary metabolites. Phytochem Rev 7:513CrossRefGoogle Scholar
  166. 166.
    Fujimori N, Ashihara H (1990) Adenine metabolism and the synthesis of purine alkaloids in flowers of Camellia plants. Phytochemistry 29:3513CrossRefGoogle Scholar
  167. 167.
    Terrasaki Y, Suzuki T, Ashihara H (1994) Purine metabolism and the biosynthesis of purine alkaloids in tea fruits during development. Plant Physiol (Life Sci Adv) 13:135Google Scholar
  168. 168.
    Li Y, Ogita S, Keya CA, Ashihara H (2008) Expression of caffeine biosynthesis genes in tea (Camellia sinensis). Z Naturforsch 63c:267Google Scholar
  169. 169.
    Li YH, Gu W, Ye S (2007) Expression and location of caffeine synthase in tea plants. Russ J Plant Physiol 54:698CrossRefGoogle Scholar
  170. 170.
    Baumann TW, Wanner H (1972) Untersuchungen Aber den Transport von Kaffein in der Kaffeepflanze (Coffea arabica). Planta 108:11CrossRefGoogle Scholar
  171. 171.
    Mosli Waldhauser SS, Baumann TW (1996) Compartmentation of caffeine and related purine alkaloids depends exclusively on the physical chemistry of their vacuolar complex formation with chlorogenic acids. Phytochemistry 42:985CrossRefGoogle Scholar
  172. 172.
    Kato A, Crozier A, Ashihara H (1998) Subcellular localization of the N-3 methyltransferase involved in caffeine biosynthesis in tea. Phytochemistry 48:777CrossRefGoogle Scholar
  173. 173.
    Kumar V, Satyanarayana KV, Ramakrishna A, Chandrashekar A, Ravishankar GA (2007) Evidence for localization of N-methyltransferase (MMT) of caffeine biosynthetic pathway in vacuolar surface of Coffea canephora endosperm elucidated through localization of GUS reporter gene driven by NMT promoter. Curr Sci 93:383Google Scholar
  174. 174.
    Foyer CH (1984) Photosynthesis. Cell biology: a series of monographs, vol. 1. Wiley, New YorkGoogle Scholar
  175. 175.
    Kodama Y, Shinya T, Sano H (2008) Dimerization of N-methyltransferases involved in caffeine biosynthesis. Biochimie 90:547CrossRefGoogle Scholar
  176. 176.
    Zrenner R, Stitt M, Sonnewald U, Boldt R (2006) Pyrimidine and purine biosynthesis and degradation in plants. Annu Rev Plant Biol 57:805CrossRefGoogle Scholar
  177. 177.
    Hung W-F, Chen L-J, Boldt R, Sun C-W, Li H-M (2004) Characterization of Arabidopsis glutamine phosphoribosyl pyrophosphate amidotransferase-deficient mutants. Plant Physiol 135:1314Google Scholar
  178. 178.
    Smith PC, Mann A, Goggin D, Atkins C (1998) Air synthetase in cowpea nodules: a single gene product targeted to two organelles? Plant Mol Biol 36:811CrossRefGoogle Scholar
  179. 179.
    Atkins CA, Smith P, Storer PJ (1997) Reexamination of the intracellular localization of de novo purine synthesis in cowpea nodules. Plant Physiol 113:127CrossRefGoogle Scholar
  180. 180.
    van der Graaff E, Hooykaas P, Lein W, Lerchl J, Kunze G, Sonnewald U, Boldt R (2004) Molecular analysis of “de novo” purine biosynthesis in solanaceous species and in Arabidopsis thaliana. Front Biosci 9:1803CrossRefGoogle Scholar
  181. 181.
    Schoor S, Farrow S, Blaschke H, Lee S, Perry G, von Schwartzenberg K, Emery N, Moffatt B (2011) Adenosine kinase contributes to cytokinin interconversion in Arabidopsis. Plant Physiol 157:659CrossRefGoogle Scholar
  182. 182.
    Jorgensen K, Rasmussen AV, Morant M, Nielsen AH, Bjarnholt N, Zagrobelny M, Bak S, Moller BL (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr Opin Plant Biol 8:280CrossRefGoogle Scholar
  183. 183.
    Deng W, Li M, Gu C, Li D, Ma L, Jin Y, Wan X (2015) Low caffeine content in novel grafted tea with Camellia sinensis as scions and Camellia oleifera as stocks. Nat Prod Commun 10:789Google Scholar
  184. 184.
    Kato M, Kitao N, Ishida M, Morimoto H, Irino F, Mizuno K (2010) Expression for caffeine biosynthesis and related enzymes in Camellia sinensis. Z Naturforsch 65c:245Google Scholar
  185. 185.
    Mohanpuria P, Kumar V, Joshi R, Gulati A, Ahuja P, Yadav S (2009) Caffeine biosynthesis and degradation in tea [Camellia sinensis (L.) O. Kuntze] is under developmental and seasonal regulation. Mol Biotechnol 43:104CrossRefGoogle Scholar
  186. 186.
    Bailey BA, Bae H, Strem MD, Antunez de Mayolo G, Guiltinan MJ, Verica JA, Maximova SN, Bowers JH (2005) Developmental expression of stress response genes in Theobroma cacao leaves and their response to Nep1 treatment and a compatible infection by Phytophthora megakarya. Plant Physiol Biochem 43:611CrossRefGoogle Scholar
  187. 187.
    Bailey BA, Strem MD, Bae H, de Mayolo GA, Guiltinan MJ (2005) Gene expression in leaves of Theobroma cacao in response to mechanical wounding, ethylene, and/or methyl jasmonate. Plant Sci 168:1247CrossRefGoogle Scholar
  188. 188.
    Kumar A, Giridhar P (2015) Salicylic acid and methyljasmonate restore the transcription of caffeine biosynthetic N-methyltransferases from a transcription inhibition noticed during late endosperm maturation in coffee. Plant Gene 4:38CrossRefGoogle Scholar
  189. 189.
    Kumar A, Simmi PS, Naik GK, Giridhar P (2015) RP-HPLC and transcript profile indicate increased leaf caffeine in Coffea canephora plants by light. J Biol Earth Sci 5:1Google Scholar
  190. 190.
    Kumar A, Naik GK, Simmi PS, Giridhar P (2015) Salinity and drought response alleviate caffeine content of young leaves of Coffea canephora var. Robusta cv. S274. J Appl Biol Biotechnol 3:50CrossRefGoogle Scholar
  191. 191.
    Deng WW, Li Y, Ogita S, Ashihara H (2008) Fine control of caffeine biosynthesis in tissue cultures of Camellia sinensis. Phytochem Lett 1:195CrossRefGoogle Scholar
  192. 192.
    Yu CL, Kale Y, Gopishetty S, Louie TM, Subramanian M (2008) A novel caffeine dehydrogenase in Pseudomonas sp. strain CBB1 oxidizes caffeine to trimethyluric acid. J Bacteriol 190:772CrossRefGoogle Scholar
  193. 193.
    Kalberer P (1964) Untersuchungen zum Abbau des Kaffeins in den Blattern von Coffea arabica. Beril Schw Bot Geselshaft 74:62Google Scholar
  194. 194.
    Kalberer P (1965) Breakdown of caffeine in the leaves of Coffea arabica L. Nature 205:597CrossRefGoogle Scholar
  195. 195.
    Suzuki T, Waller GR (1984) Biosynthesis and biodegradation of caffeine, theobromine, and theophylline in Coffea arabica L. fruits. J Agric Food Chem 32:845CrossRefGoogle Scholar
  196. 196.
    Suzuki T, Waller GR (1984) Biodegradation of caffeine: formation of theophylline and caffeine in mature Coffea arabica fruits. J Sci Food Agric 35:66CrossRefGoogle Scholar
  197. 197.
    Ashihara H, Monteiro AM, Moritz T, Gillies FM, Crozier A (1996) Catabolism of caffeine and related purine alkaloids in leaves of Coffea arabica L. Planta 198:334CrossRefGoogle Scholar
  198. 198.
    Yin Y, Katahira R, Ashihara H (2015) Metabolism of purine alkaloids and xanthine in leaves of maté (Ilex paraguariensis). Nat Prod Commun 10:707Google Scholar
  199. 199.
    Moffatt BA, Ashihara H (2002) Purine and pyrimidine nucleotide synthesis and metabolism. In: The Arabidopsis book, vol 1. American Society of Plant Biologists, Rockville, MD, p 1Google Scholar
  200. 200.
    Munoz A, Raso M, Pineda M, Piedras P (2006) Degradation of ureidoglycolate in French bean (Phaseolus vulgaris) is catalysed by a ubiquitous ureidoglycolate urea-lyase. Planta 224:175CrossRefGoogle Scholar
  201. 201.
    Winkler RG, Blevins DG, Randall DD (1988) Ureide catabolism in soybeans. Plant Physiol 86:1084CrossRefGoogle Scholar
  202. 202.
    Deng W-W, Ashihara H (2010) Profiles of purine metabolism in leaves and roots of Camellia sinensis seedlings. Plant Cell Physiol 51:2105CrossRefGoogle Scholar
  203. 203.
    Nazario GM, Lovatt CJ (1993) Regulation of purine metabolism in intact leaves of Coffea arabica. Plant Physiol 103:1195CrossRefGoogle Scholar
  204. 204.
    Ashihara H, Crozier A (1999) Biosynthesis and catabolism of caffeine in low-caffeine-containing species of Coffea. J Agric Food Chem 47:3425CrossRefGoogle Scholar
  205. 205.
    Ashihara H, Shimizu H, Takeda Y, Suzuki T, Gillies FM, Crozier A (1995) Caffeine metabolism in high and low caffeine containing cultivars of Camellia sinensis. Z Naturforsch 50c:602Google Scholar
  206. 206.
    Ashihara H, Kato M, Ye CX (1998) Biosynthesis and metabolism of purine alkaloids in leaves of cocoa tea (Camellia ptilophylla). J Plant Res 111:599CrossRefGoogle Scholar
  207. 207.
    Ito E, Crozier A, Ashihara H (1997) Theophylline metabolism in higher plants. Biochim Biophys Acta 1336:323CrossRefGoogle Scholar
  208. 208.
    Mazzafera P (2004) Catabolism of caffeine in plants and microorganisms. Front Biosci 9:1348CrossRefGoogle Scholar
  209. 209.
    Madyastha KM, Sridhar GR (1998) A novel pathway for the metabolism of caffeine by a mixed culture consortium. Biochem Biophys Res Commun 249:178CrossRefGoogle Scholar
  210. 210.
    Yu CL, Louie TM, Summers R, Kale Y, Gopishetty S, Subramanian M (2009) Two distinct pathways for metabolism of theophylline and caffeine are coexpressed in Pseudomonas putida CBB5. J Bacteriol 191:4624CrossRefGoogle Scholar
  211. 211.
    Summers RM, Louie TM, Yu CL, Subramanian M (2011) Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source. Microbiology 157:583CrossRefGoogle Scholar
  212. 212.
    Summers RM, Louie TM, Yu C-L, Gakhar L, Louie KC, Subramanian M (2012) Novel, highly specific N-demethylases enable bacteria to live on caffeine and related purine alkaloids. J Bacteriol 194:2041CrossRefGoogle Scholar
  213. 213.
    Scheline RR (1991) CRC handbook of mammalian metabolism of plant compounds. CRC Press, Boca Raton, FLGoogle Scholar
  214. 214.
    Arnaud MJ (2011) Pharmacokinetics and metabolism of natural methylxanthines in animal and man. In: Arnaud MJ (ed) Methylxanthines, vol 200, Handbook of experimental pharmacology. Springer, Heidelberg, p 33CrossRefGoogle Scholar
  215. 215.
    Molisch H (1937) Der Einfluss einer Pflanze auf die andere-Allelopathie. Gustav Fischer, JenaGoogle Scholar
  216. 216.
    Anaya AL, Cruz-Ortega R, Waller GR (2006) Metabolism and ecology of purine alkaloids. Front Biosci 11(Suppl 1):2354CrossRefGoogle Scholar
  217. 217.
    Lovett JV, Hoult AHC (1998) Allelopathy in plants. In: Roberts MF, Wink MP (eds) Alkaloids: biochemistry, ecology, and medicinal applications. Plenum, London, p 337CrossRefGoogle Scholar
  218. 218.
    Anaya AL, Ramos L, Hernandez JG, Cruz-Ortega R (1987) Allelopathy in Mexico. In: Waller GR (ed) Allelochemicals: role in agriculture and forestry, Symposium series 330. American Chemical Society, Washington, DC, p 89CrossRefGoogle Scholar
  219. 219.
    Waller GR, Kumari D, Friedman J, Friedman N, Chou CH (1986) Caffeine autotoxicity in Coffea arabica L. In: Putnam AR, Tang C-S (eds) The science of allelopathy. Wiley, New York, p 243Google Scholar
  220. 220.
    Friedman J, Waller G (1983) Caffeine hazards and their prevention in germinating seeds of coffee (Coffea arabica L.). J Chem Ecol 9:1099CrossRefGoogle Scholar
  221. 221.
    Baumann TW, Gabriel H (1984) Metabolism and excretion of caffeine during germination of Coffea arabica L. Plant Cell Physiol 25:1431Google Scholar
  222. 222.
    Chou C-H, Waller G (1980) Possible allelopathic constituents of Coffea arabica. J Chem Ecol 6:643CrossRefGoogle Scholar
  223. 223.
    Rizvi SJH, Mukerji D, Mathur SN (1981) Selective phyto-toxicity of 1,3,7-trimethylxanthine between Phaseolus mungo and some weeds. Agric Biol Chem 45:1255Google Scholar
  224. 224.
    Smyth D (1992) Effect of methylxanthine treatment on rice seedling growth. J Plant Growth Regul 11:125CrossRefGoogle Scholar
  225. 225.
    Sasamoto H, Fujii Y, Ashihara H (2015) Effect of purine alkaloids on the proliferation of lettuce cells derived from protoplasts. Nat Prod Commun 10:751Google Scholar
  226. 226.
    Sasamoto H, Murashige-Baba T, Inoue A, Sato T, Hayashi S, Hasegawa A (2013) Development of a new method for bioassay of allelopathy using protoplasts of a leguminous plant Mucuna pruriens with a high content of the allelochemical l-DOPA. J Plant Stud 2:71CrossRefGoogle Scholar
  227. 227.
    Kihlman BA (1977) Caffeine and chromosomes. Elsevier, AmsterdamGoogle Scholar
  228. 228.
    Kihlman B (1949) The effect of purine derivatives on chromosomes. Hereditas 35:393Google Scholar
  229. 229.
    Kihlman B, Leven A (1949) The cytological effect of caffeine. Hereditas 35:109Google Scholar
  230. 230.
    Mineyuki Y, Letham DS, Hocart CH (1989) New 3-substituted xanthines: potent inhibitors of cell plate formation. Cell Biol Int Rep 13:129CrossRefGoogle Scholar
  231. 231.
    Amino S, Nagata T (1996) Caffeine-induced uncoupling of mitosis from DNA replication in tobacco BY-2 cells. J Plant Res 109:219CrossRefGoogle Scholar
  232. 232.
    Manandhar G, Apostolakos P, Galatis B (1996) Cell division of binuclear cells induced by caffeine: spindle organization and determination of division plane. J Plant Res 109:265CrossRefGoogle Scholar
  233. 233.
    Deng WW, Katahira R, Ashihara H (2015) Short-term effect of caffeine on purine, pyrimidine and pyridine metabolism in rice (Oryza sativa) seedlings. Nat Prod Commun 10:737Google Scholar
  234. 234.
    Shimazaki A, Ashihara H (1982) Adenine and guanine salvage in cultured cells of Catharanthus roseus. Ann Bot 50:531CrossRefGoogle Scholar
  235. 235.
    Shimazaki A, Hirose F, Ashihara H (1982) Changes in adenine nucleotide levels and adenine salvage during the growth of Vinca rosea cells in suspension culture. Z Pflanzenphysiol 106:191CrossRefGoogle Scholar
  236. 236.
    Yin Y, Katahira R, Ashihara H (2014) Metabolism of purine nucleosides and bases in suspension-cultured Arabidopsis thaliana cells. Eur Chem Bull 3:925Google Scholar
  237. 237.
    Yin Y, Shimano F, Ashihara H (2007) Involvement of rapid nucleotide synthesis in recovery from phosphate starvation of Catharanthus roseus cells. J Exp Bot 58:1025CrossRefGoogle Scholar
  238. 238.
    Kanamori-Fukuda I, Ashihara H, Komamine A (1981) Pyrimidine nucleotide biosynthesis in Vinca rosea cells: changes in the activity of de novo and salvage pathways during growth in a suspension culture. J Exp Bot 32:69CrossRefGoogle Scholar
  239. 239.
    Katahira R, Ashihara H (2006) Dual function of pyrimidine metabolism in potato (Solanum tuberosum) plants: pyrimidine salvage and supply of β-alanine to pantothenic acid synthesis. Physiol Plant 127:38CrossRefGoogle Scholar
  240. 240.
    Watanabe S, Matsumoto M, Hakomori Y, Takagi H, Shimada H, Sakamoto A (2014) The purine metabolite allantoin enhances abiotic stress tolerance through synergistic activation of abscisic acid metabolism. Plant Cell Environ 37:1022CrossRefGoogle Scholar
  241. 241.
    Deng WW, Sasamoto H, Ashihara H (2015) Effect of caffeine on the expression pattern of water-soluble proteins in rice (Oryza sativa) seedlings. Nat Prod Commun 10:733Google Scholar
  242. 242.
    Epifanio JA (1981) Ecology of the cafetalero agroecosystem. Universidad Nacional Autonoma de Mexico, Mexico, DFGoogle Scholar
  243. 243.
    Waller GR (1989) Biochemical frontiers of allelopathy. Biol Plant 31:418CrossRefGoogle Scholar
  244. 244.
    Nathanson JA (1984) Caffeine and related methylxanthines: possible naturally occurring pesticides. Science 226:184CrossRefGoogle Scholar
  245. 245.
    Hollingsworth RG, Armstrong JW, Campbell E (2002) Pest control caffeine as a repellent for slugs and snails. Nature 417:915CrossRefGoogle Scholar
  246. 246.
    Hollingsworth RG, Armstrong JW, Campbell E (2003) Caffeine as a novel toxicant for slugs and snails. Ann Appl Biol 142:91CrossRefGoogle Scholar
  247. 247.
    Aneja M, Gianfagna T (2001) Induction and accumulation of caffeine in young, actively growing leaves of cocoa (Theobroma cacao L.) by wounding or infection with Crinipellis perniciosa. Physiol Mol Plant Pathol 59:13CrossRefGoogle Scholar
  248. 248.
    Kim Y-S, Lim S, Kang K-K, Jung Y-J, Lee Y-H, Choi Y-E, Sano H (2011) Resistance against beet armyworms and cotton aphids in caffeine-producing transgenic chrysanthemum. Plant Biotechnol 28:393CrossRefGoogle Scholar
  249. 249.
    Kim YS, Lim S, Yoda H, Choi CS, Choi YE, Sano H (2011) Simultaneous activation of salicylate production and fungal resistance in transgenic chrysanthemum producing caffeine. Plant Signal Behav 6:409CrossRefGoogle Scholar
  250. 250.
    Kim YS, Uefuji H, Ogita S, Sano H (2006) Transgenic tobacco plants producing caffeine: a potential new strategy for insect pest control. Transgenic Res 15:667CrossRefGoogle Scholar
  251. 251.
    Kim YS, Sano H (2008) Pathogen resistance of transgenic tobacco plants producing caffeine. Phytochemistry 69:882CrossRefGoogle Scholar
  252. 252.
    Kim YS, Choi YE, Sano H (2010) Plant vaccination: stimulation of defense system by caffeine production in planta. Plant Signal Behav 5:489CrossRefGoogle Scholar
  253. 253.
    Crozier TWM, Stalmach A, Lean MEJ, Crozier A (2012) Espresso coffees, caffeine and chlorogenic acid intake: potential health implications. Food Funct 3:30CrossRefGoogle Scholar
  254. 254.
    Crozier A, Ashihara H (2006) The cup that cheers. Caffeine biosynthesis: biochemistry and molecular biology. Biochemist 28(5):23Google Scholar
  255. 255.
    Ogita S, Uefuji H, Yamaguchi Y, Nozomu K, Sano H (2003) Producing decaffeinated coffee plants. Nature 423:823CrossRefGoogle Scholar
  256. 256.
    Ogita S, Uefuji H, Morimoto M, Sano H (2004) Application of RNAi to confirm theobromine as the major intermediate for caffeine biosynthesis in coffee plants with potential for construction of decaffeinated varieties. Plant Mol Biol 54:931CrossRefGoogle Scholar
  257. 257.
    Ogita S, Uefuji H, Morimoto M, Sano H (2005) Metabolic engineering of caffeine production. Plant Biotechnol 22:461CrossRefGoogle Scholar
  258. 258.
    Ashihara H, Ogita S, Crozier A (2011) Purine alkaloid metabolism. In: Ashihara H, Crozier A, Komamine A (eds) Plant metabolism and biotechnology. Wiley, Chichester, UK, p 163CrossRefGoogle Scholar
  259. 259.
    Mohanpuria P, Kumar V, Ahuja P, Yadav S (2011) Producing low-caffeine tea through post-transcriptional silencing of caffeine synthase mRNA. Plant Mol Biol 76:523CrossRefGoogle Scholar
  260. 260.
    Ashihara H, Zheng XQ, Katahira R, Morimoto M, Ogita S, Sano H (2006) Caffeine biosynthesis and adenine metabolism in transgenic Coffea canephora plants with reduced expression of N-methyltransferase genes. Phytochemistry 67:882CrossRefGoogle Scholar
  261. 261.
    Mohanpuria P, Kumar V, Yadav S (2010) Tea caffeine: metabolism, functions, and reduction strategies. Food Sci Biotechnol 19:275CrossRefGoogle Scholar
  262. 262.
    Nakayama F, Mizuno K, Kato M (2015) Biosynthesis of caffeine underlying the diversity of motif B′ methyltransferase. Nat Prod Commun 10:799Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Hiroshi Ashihara
    • 1
    Email author
  • Kouichi Mizuno
    • 2
  • Takao Yokota
    • 3
  • Alan Crozier
    • 4
  1. 1.Department of BiologyOchanomizu UniversityTokyoJapan
  2. 2.Faculty of Bioresource of ScienceAkita Prefectural UniversityAkitaJapan
  3. 3.Department of BiosciencesTeikyo UniversityUtsunomiyaJapan
  4. 4.Department of NutritionUniversity of CaliforniaDavisUSA

Personalised recommendations