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.
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References
Ashihara H, Crozier A (2001) Caffeine: a well known but little mentioned compound in plant science. Trends Plant Sci 6:407
Runge FF (1820) Neueste phytochemische Entdeckungen zur Begründung einer wissenschaftlichen Phytochemie. In: Phytochemische Entdeckungen. Reimer, Berlin, p 204
Von Giese F (1820) Vermischte Notizen. 1. Kaffeestoff und Salzgehalt des Quassia Extrakts. Ann Chem 4:240
Oudry V (1927) Thein, eine organische Salzbase im Thee (Thea chinesis). Mag Pharm 19:49
Stenhouse J (1843) Über Thein und seine Darstellung. Liebigs Ann Chem 45:366
Daniell WF (1865) On the kola-nut of tropical West Africa (the guru nut of Soudan). Pharm J 6:450
Woskresensky A (1842) Über das Theobromin. Liebigs Ann Chem 41:125
Salomon G. Über Paraxanthin und Heteroxanthin. Ber Dtsch Chem Ges 18:3406
Chou CH, Waller GR (1980) Possible allelopathic constituents of Coffea arabica. J Chem Ecol 6:643
Fischer E, Ach L (1895) Synthese des Caffeins. Ber Dtsch Chem Ges 28:3135
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 120:579
Kato M, Mizuno K, Crozier A, Fujimura T, Ashihara H (2000) A gene encoding caffeine synthase from tea leaves. Nature 406:956
Ashihara H, Crozier A (1999) Biosynthesis and metabolism of caffeine and related purine alkaloids in plants. Adv Bot Res 30:117
Sano H, Kim Y-S, Choi Y-E (2013) Like cures like: caffeine immunizes plants against biotic stresses. Adv Bot Res 68:273
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 1
Kihlman BA (1977) Occurrence and biosynthesis of methylated oxypurines in plants. In: Caffeine and chromosome. Elsevier, Amsterdam, p 11
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, DC
O’Connell FD (1969) Isolation of caffeine from Banisteriopsis inebrians (Malpighiaceae). Naturwissenschaften 56:139
Stewart I (1985) Identification of caffeine in citrus flowers and leaves. J Agric Food Chem 33:1163
Kretschmar JA, Baumann TW (1999) Caffeine in Citrus flowers. Phytochemistry 52:19
Smith AR, Pryer KM, Schuettpelz E, Korall P, Schneider H, Wolf PG (2006) A classification for extant ferns. Taxon 55:705
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 161:105
Nagata T, Sakai S (1984) Differences in caffeine, flavonols and amino acids contents in leaves of cultivated species of Camellia. Jpn J Breed 34:459
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 35:1
Nagata T, Sakai S (1985) Purine base pattern of Camellia irrawadiensis. Phytochemistry 24:2271
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 36:30
Johnson TB (1937) Purines in the plant kingdom: the discovery of a new purine in tea. J Am Chem Soc 59:1261
Ye C, Lin Y, Su J, Zhang H (1999) Purine alkaloids in Camellia assamica var. kucha Chang et Wang. Acta Scientiarum Naturalium Universitatis Sunyatseni 38:82
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 60:129
Deng W-W (2011) Biosynthesis of secondary metabolites in tea plants. PhD thesis, Ochanomizu University, Tokyo
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 229:559
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 33:410
Ashihara H, Kubota H (1986) Patterns of adenine metabolism and caffeine biosynthesis in different parts of tea seedlings. Physiol Plant 68:275
van Breda SV, Merwe CF, Robbertse H, Apostolides Z (2013) Immunohistochemical localization of caffeine in young Camellia sinensis (L.) O. Kuntze (tea) leaves. Planta 237:849
Petracco M (2005) Our everyday cup of coffee: the chemistry behind its magic. J Chem Educ 82:1161
Mazzafera P, Carvalho A (1992) Breeding for low seed caffeine content of coffee (Coffea L.) by interspecific hybridization. Euphytica 59:55
Anthony F, Clifford MN, Noirot M (1993) Biochemical diversity in the genus Coffea L.: chlorogenic acids, caffeine and mozambioside contents. Genet Resour Crop Evol 40:61
Silvarolla MB, Mazzafera P, Fazuoli LC (2004) Plant biochemistry: a naturally decaffeinated arabica coffee. Nature 429:826
Baumann TW, Oechslin M, Wanner H (1976) Caffeine and methylated uric acids: chemical patterns during vegetative development of Coffea liberica. Biochem Physiol Pflanzen 170:217
Petermann J, Baumann TW (1983) Metabolic relations between methylxanthines and methyluric acids in Coffea. Plant Physiol 73:961
Zheng XQ, Ashihara H (2004) Distribution, biosynthesis and function of purine and pyridine alkaloids in Coffea arabica seedlings. Plant Sci 166:807
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 25:613
Fujimori N, Ashihara H (1994) Biosynthesis of theobromine and caffeine in developing leaves of Coffea arabica. Phytochemistry 36:1359
Keller H, Wanner H, Baumann TW (1972) Kaffeinsynthese in Fruchten und Gewebekulturen von Coffea arabica. Planta 108:339
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 171:242
Clifford MN, Ramirez-Martinez JR (1990) Chlorogenic acids and purine alkaloids contents of maté (Ilex paraguariensis) leaf and beverage. Food Chem 35:13
Alikaridis F (1987) Natural constituents of Ilex species. J Ethnopharmacol 20:121
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 2:87
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 59:275
Mazzafera P (1994) Caffeine, theobromine and theophylline distribution in Ilex paraguariensis. Rev Brasil Fisiol Veg 6:149
Crozier A, Ashihara H, Tomas-Barberan F (eds) (2012) Teas, cocoa and coffee: plant secondary metabolites and health. Wiley-Blackwell, Oxford, UK
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 61:427
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 43:560
Hammerstone JF Jr, Romanczyk LJ Jr, Aitkent WM (1994) Purine alkaloid distribution within Herrania and Theobroma. Phytochemistry 35:1237
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 542
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 41:977
Gurney KA, Evans LV, Robinson DS (1991) Extraction of purine alkaloids from cocoa tissues and determination by high-performance liquid chromatography. Phytochem Anal 2:15
Senanayake UM, Wijesekera ROB (1971) Theobromine and caffeine content of the cocoa bean during its growth. J Sci Food Agric 22:262
Sotelo A, Alvarez RG (1991) Chemical composition of wild-Theobroma species and their comparison to the cacao bean. J Agric Food Chem 39:1940
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 49:5046
Zheng X-Q, Koyama Y, Nagai C, Ashihara H (2004) Biosynthesis, accumulation and degradation of theobromine in developing Theobroma cacao fruits. J Plant Physiol 161:363
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 180:398
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 74:629
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 105:25
Weckerle CS, Stutz MA, Baumann TW (2003) Purine alkaloids in Paullinia. Phytochemistry 64:735
Baumann TW, Schulthess BH, Hanni K (1995) Guarana (Paullinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 39:1063
Ashihara H, Yokota T, Crozier A (2013) Biosynthesis and catabolism of purine alkaloids. Adv Bot Res 68:111
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 23:7289
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 14:765
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 257
Bonner J (1950) Plant biochemistry. Academic Press, New York
Bresler HW (1904) Uber die Bestimmung der Nucleinbasen im Safte von Beta vulgaris. Hoppe Seyler’s Z Physiol Chem 4:535
Weevers T (1930) Die Funkion der Xanthinderivate im Pflanzenstoffwechsel. Arch Neerl Sci 3B(5):111
Anderson L, Gibbs M (1962) The biosynthesis of caffeine in the coffee plant. J Biol Chem 237:1941
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 80:548
Inoue T, Kawamura Y (1961) Studies on biogenesis of tea components. II. Formation of caffeine in excised tea shoots. Chem Pharm Bull 9:236
Inoue T (1972) Studies on biogenesis of tea components. IV. Incorporation of glycine-2-14C to caffeine. Proc Hoshi Coll Pharm (Tokyo) 13:60
Inoue T, Adachi F (1962) Studies on biogenesis of tea components. III. The origin of the methyl groups in caffeine. Chem. Pharm Bull 10:1212
Serenkov GP, Proiser E (1961) Biosynthesis of caffeine in tea leaves. Dokl Akad Nauk USSR 140:716
Proiser E, Serenkov GP (1963) Caffeine biosynthesis in tea leaves. Biokhimiya (Moscow) 28:857
Konishi S, Ozawa M, Takahashi E (1972) Metabolic conversion of N-methyl carbon of γ-glutamylmethylamide to caffeine in tea plants. Plant Cell Physiol 13:365
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 13:695
Suzuki T (1972) The participation of S-adenosylmethionine in the biosynthesis of caffeine in the tea plant. FEBS Lett 24:18
Suzuki T (1973) Metabolism of methylamine in the tea plant (Thea sinensis L.). Biochem J 132:753
Suzuki T, Takahashi E (1975) Metabolism of xanthine and hypoxanthine in the tea plant (Thea sinensis L.). Biochem J 146:79
Suzuki T, Takahashi E (1976) Caffeine biosynthesis in Camellia sinensis. Phytochemistry 15:1235
Looser E, Baumann TW, Wanner H (1974) The biosynthesis of caffeine in the coffee plant. Phytochemistry 13:2515
Ogutuga DBA, Northcote DH (1970) Caffeine formation in tea callus tissue. J Exp Bot 21:258
Ogutuga DBA, Northcote DH (1970) Biosynthesis of caffeine in tea callus tissue. Biochem J 117:715
Keller H, Wanner H, Baumann TW (1972) Kaffeinsynthese in Früchten und Gewebekulturen von Coffea arabica. Planta 108:339
Suzuki T, Takahashi E (1976) Metabolism of methionine and biosynthesis of caffeine in the tea plant (Camellia sinensis L.). Biochem J 160:171
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 160:181
Loomis WD (1969) Removal of phenolic compounds during the isolation of plant enzymes. In: Methods in enzymology, vol 13. Academic Press, New York, p 555
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 146:87
Roberts MF, Waller GR (1979) N-Methyltransferases and 7-methyl-N9-nucleoside hydrolase activity in Coffea arabica and the biosynthesis of caffeine. Phytochemistry 18:451
Baumann TW, Koetz R, Morath P (1983) N-Methyltransferase activities in suspension cultures of Coffea arabica L. Plant Cell Rep 2:33
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 2:109
Negishi O, Ozawa T, Imagawa H (1985) Methylation of xanthosine by tea-leaf extracts and caffeine biosynthesis. Agric Biol Chem 49:887
Negishi O, Ozawa T, Imagawa H (1988) N-Methylnucleosidase from tea leaves. Agric Biol Chem 52:169
Ashihara H, Nobusawa E (1981) Metabolic fate of [8-14C]adenine and [8-14C]hypoxanthine in higher plants. Z Pflanzenphysiol 104:443
Nobusawa E, Ashihara H (1983) Purine metabolism in cotyledons and embryonic axes of black gram (Phaseolus mungo L.) seedlings. Int J Biochem 15:1059
Ashihara H, Kubota H (1987) Biosynthesis of purine alkaloids in Camellia plants. Plant Cell Physiol 28:535
Ashihara H (1993) Purine metabolism and the biosynthesis of caffeine in maté leaves. Phytochemistry 33:1427
Negishi O, Ozawa T, Imagawa H (1992) Biosynthesis of caffeine from purine nucleotides in tea plant. Biosci Biotechnol Biochem 56:499
Suzuki T, Ashihara H, Waller GR (1992) Purine and purine alkaloid metabolism in Camellia and Coffea plants. Phytochemistry 31:2575
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 499:50
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 103:1203
Ashihara H, Monteiro AM, Gillies FM, Crozier A (1996) Biosynthesis of caffeine in leaves of coffee. Plant Physiol 111:747
Schulthess BH, Morath P, Baumann TW (1996) Caffeine biosynthesis starts with the metabolically channelled formation of 7-methyl-XMP. A new hypothesis. Phytochemistry 41:169
Schulthess BH, Baumann TW (1995) Are xanthosine and 7-methylxanthosine caffeine precursors? Phytochemistry 39:1363
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 547:56
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 599
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 17:1577
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 40
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 98:629
Mosli Waldhauser SS, Gillies FM, Crozier A, Baumann TW (1997) Separation of the N-7 methyltransferase, the key enzyme in caffeine biosynthesis. Phytochemistry 45:1407
Kato M, Mizuno K, Crozier A, Fujimura T, Ashihara H (2000) Plant biotechnology: caffeine synthase gene from tea leaves. Nature 406:956
Moisyadi S, Neupane KR, Stiles JI (1998) Cloning and characterization of a cDNA encoding xanthosine-N7-methyltransferase from coffee (Coffea arabica). Acta Hort 461:367
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 327
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 59:221
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 534:75
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 815
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 276:8213
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 132:372
Ashihara H, Sano H, Crozier A (2008) Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69:841
Negishi O, Ozawa T, Imagawa H (1985) Conversion of xanthosine into caffeine in tea plants. Agric Biol Chem 49:251
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 54:593
Fujimori N, Suzuki T, Ashihara H (1991) Seasonal variations in biosynthetic capacity for the synthesis of caffeine in tea leaves. Phytochemistry 30:2245
McCarthy AA, McCarthy JG (2007) The structure of two N-methyltransferases from the caffeine biosynthetic pathway. Plant Physiol 144:879
Ashihara H, Gillies FM, Crozier A (1997) Metabolism of caffeine and related purine alkaloids in leaves of tea (Camellia sinensis L.). Plant Cell Physiol 38:413
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 275:125
Kato M, Mizuno K (2004) Caffeine synthase and related methyltransferases in plants. Front Biosci 9:1833
Joshi CP, Chiang VL (1998) Conserved sequence motifs in plant S-adenosyl-l-methionine-dependent methyltransferases. Plant Mol Biol 37:663
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 367:9
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 12:949
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 98:4788
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 448:123
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 146:455
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 19:32
Murata J, Roepke J, Gordon H, De Luca V (2008) The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell 20:524
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 253
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 15:1704
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 345:1181
Pichersky E, Lewinsohn E (2011) Convergent evolution in plant specialized metabolism. Annu Rev Plant Biol 62:549
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 241:179
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 452:1060
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 14:765
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 19
Arabidopsis-Genome-Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796
International-Rice-Genome-Sequencing-Project (2005) The map-based sequence of the rice genome. Nature 436:793
Zrenner R, Ashihara H (2011) Nucleotide metabolism. In: Ashihara H, Crozier A, Komamine A (eds) Plant metabolism and biotechnology. Wiley, Chichester, UK, p 135
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 254:145
Yabuki N, Ashihara H (1991) Catabolism of adenine nucleotides in suspension-cultured plant cells. Biochim Biophys Acta 1073:474
Fujimori N, Ashihara H (1993) Biosynthesis of caffeine in flower buds of Camellia sinensis. Ann Bot 71:279
Baumann TW (2015) Revisiting caffeine biosynthesis — speculations about the proximate source of its purine ring. Nat Prod Commun 10:793
Kremers RE (1954) Speculation on DPN as a biochemical precursor of caffeine and trigonelline in coffee. J Am Pharm Assoc 43:423
Negishi O, Ozawa T, Imagawa H (1994) Guanosine deaminase and guanine deaminase from tea leaves. Biosci Biotechnol Biochem 58:1277
Ashihara H, Takasawa Y, Suzuki T (1997) Metabolic fate of guanosine in higher plants. Physiol Plant 100:909
Mager J, Magasanik B (1960) Guanosine-5′-phosphate reductase and its role in the interconversion of purine nucleotides. J Biol Chem 235:1474
Stephens RW, Whittaker VK (1973) Calf thymus GMP reductase: control by XMP. Biochem Biophys Res Commun 53:975
Renart MF, Sillero A (1974) GMP reductase in Artemia salina. Biochim Biophys Acta 341:178
Le Floc’h F, Lafleuriel J, Guillot A (1982) Interconversion of purine nucleotides in Jerusalem artichoke shoots. Plant Sci Lett 27:309
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 2:129
Shoji T, Hashimoto T (2011) Nicotine biosynthesis. In: Ashihara H, Crozier A, Komamine A (eds) Plant metabolism and biotechnology. Wiley, Chichester UK, p 191
Yazaki K, Sugiyama A, Morita M, Shitan N (2008) Secondary transport as an efficient membrane transport mechanism for plant secondary metabolites. Phytochem Rev 7:513
Fujimori N, Ashihara H (1990) Adenine metabolism and the synthesis of purine alkaloids in flowers of Camellia plants. Phytochemistry 29:3513
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) 13:135
Li Y, Ogita S, Keya CA, Ashihara H (2008) Expression of caffeine biosynthesis genes in tea (Camellia sinensis). Z Naturforsch 63c:267
Li YH, Gu W, Ye S (2007) Expression and location of caffeine synthase in tea plants. Russ J Plant Physiol 54:698
Baumann TW, Wanner H (1972) Untersuchungen Aber den Transport von Kaffein in der Kaffeepflanze (Coffea arabica). Planta 108:11
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 42:985
Kato A, Crozier A, Ashihara H (1998) Subcellular localization of the N-3 methyltransferase involved in caffeine biosynthesis in tea. Phytochemistry 48:777
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 93:383
Foyer CH (1984) Photosynthesis. Cell biology: a series of monographs, vol. 1. Wiley, New York
Kodama Y, Shinya T, Sano H (2008) Dimerization of N-methyltransferases involved in caffeine biosynthesis. Biochimie 90:547
Zrenner R, Stitt M, Sonnewald U, Boldt R (2006) Pyrimidine and purine biosynthesis and degradation in plants. Annu Rev Plant Biol 57:805
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 135:1314
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 36:811
Atkins CA, Smith P, Storer PJ (1997) Reexamination of the intracellular localization of de novo purine synthesis in cowpea nodules. Plant Physiol 113:127
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 9:1803
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 157:659
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 8:280
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 10:789
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:245
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 43:104
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 43:611
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 168:1247
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 4:38
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 5:1
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 3:50
Deng WW, Li Y, Ogita S, Ashihara H (2008) Fine control of caffeine biosynthesis in tissue cultures of Camellia sinensis. Phytochem Lett 1:195
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 190:772
Kalberer P (1964) Untersuchungen zum Abbau des Kaffeins in den Blattern von Coffea arabica. Beril Schw Bot Geselshaft 74:62
Kalberer P (1965) Breakdown of caffeine in the leaves of Coffea arabica L. Nature 205:597
Suzuki T, Waller GR (1984) Biosynthesis and biodegradation of caffeine, theobromine, and theophylline in Coffea arabica L. fruits. J Agric Food Chem 32:845
Suzuki T, Waller GR (1984) Biodegradation of caffeine: formation of theophylline and caffeine in mature Coffea arabica fruits. J Sci Food Agric 35:66
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 198:334
Yin Y, Katahira R, Ashihara H (2015) Metabolism of purine alkaloids and xanthine in leaves of maté (Ilex paraguariensis). Nat Prod Commun 10:707
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 1
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 224:175
Winkler RG, Blevins DG, Randall DD (1988) Ureide catabolism in soybeans. Plant Physiol 86:1084
Deng W-W, Ashihara H (2010) Profiles of purine metabolism in leaves and roots of Camellia sinensis seedlings. Plant Cell Physiol 51:2105
Nazario GM, Lovatt CJ (1993) Regulation of purine metabolism in intact leaves of Coffea arabica. Plant Physiol 103:1195
Ashihara H, Crozier A (1999) Biosynthesis and catabolism of caffeine in low-caffeine-containing species of Coffea. J Agric Food Chem 47:3425
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:602
Ashihara H, Kato M, Ye CX (1998) Biosynthesis and metabolism of purine alkaloids in leaves of cocoa tea (Camellia ptilophylla). J Plant Res 111:599
Ito E, Crozier A, Ashihara H (1997) Theophylline metabolism in higher plants. Biochim Biophys Acta 1336:323
Mazzafera P (2004) Catabolism of caffeine in plants and microorganisms. Front Biosci 9:1348
Madyastha KM, Sridhar GR (1998) A novel pathway for the metabolism of caffeine by a mixed culture consortium. Biochem Biophys Res Commun 249:178
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 191:4624
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 157:583
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 194:2041
Scheline RR (1991) CRC handbook of mammalian metabolism of plant compounds. CRC Press, Boca Raton, FL
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 33
Molisch H (1937) Der Einfluss einer Pflanze auf die andere-Allelopathie. Gustav Fischer, Jena
Anaya AL, Cruz-Ortega R, Waller GR (2006) Metabolism and ecology of purine alkaloids. Front Biosci 11(Suppl 1):2354
Lovett JV, Hoult AHC (1998) Allelopathy in plants. In: Roberts MF, Wink MP (eds) Alkaloids: biochemistry, ecology, and medicinal applications. Plenum, London, p 337
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 89
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 243
Friedman J, Waller G (1983) Caffeine hazards and their prevention in germinating seeds of coffee (Coffea arabica L.). J Chem Ecol 9:1099
Baumann TW, Gabriel H (1984) Metabolism and excretion of caffeine during germination of Coffea arabica L. Plant Cell Physiol 25:1431
Chou C-H, Waller G (1980) Possible allelopathic constituents of Coffea arabica. J Chem Ecol 6:643
Rizvi SJH, Mukerji D, Mathur SN (1981) Selective phyto-toxicity of 1,3,7-trimethylxanthine between Phaseolus mungo and some weeds. Agric Biol Chem 45:1255
Smyth D (1992) Effect of methylxanthine treatment on rice seedling growth. J Plant Growth Regul 11:125
Sasamoto H, Fujii Y, Ashihara H (2015) Effect of purine alkaloids on the proliferation of lettuce cells derived from protoplasts. Nat Prod Commun 10:751
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 2:71
Kihlman BA (1977) Caffeine and chromosomes. Elsevier, Amsterdam
Kihlman B (1949) The effect of purine derivatives on chromosomes. Hereditas 35:393
Kihlman B, Leven A (1949) The cytological effect of caffeine. Hereditas 35:109
Mineyuki Y, Letham DS, Hocart CH (1989) New 3-substituted xanthines: potent inhibitors of cell plate formation. Cell Biol Int Rep 13:129
Amino S, Nagata T (1996) Caffeine-induced uncoupling of mitosis from DNA replication in tobacco BY-2 cells. J Plant Res 109:219
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 109:265
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 10:737
Shimazaki A, Ashihara H (1982) Adenine and guanine salvage in cultured cells of Catharanthus roseus. Ann Bot 50:531
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 106:191
Yin Y, Katahira R, Ashihara H (2014) Metabolism of purine nucleosides and bases in suspension-cultured Arabidopsis thaliana cells. Eur Chem Bull 3:925
Yin Y, Shimano F, Ashihara H (2007) Involvement of rapid nucleotide synthesis in recovery from phosphate starvation of Catharanthus roseus cells. J Exp Bot 58:1025
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 32:69
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 127:38
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 37:1022
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 10:733
Epifanio JA (1981) Ecology of the cafetalero agroecosystem. Universidad Nacional Autonoma de Mexico, Mexico, DF
Waller GR (1989) Biochemical frontiers of allelopathy. Biol Plant 31:418
Nathanson JA (1984) Caffeine and related methylxanthines: possible naturally occurring pesticides. Science 226:184
Hollingsworth RG, Armstrong JW, Campbell E (2002) Pest control caffeine as a repellent for slugs and snails. Nature 417:915
Hollingsworth RG, Armstrong JW, Campbell E (2003) Caffeine as a novel toxicant for slugs and snails. Ann Appl Biol 142:91
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 59:13
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 28:393
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 6:409
Kim YS, Uefuji H, Ogita S, Sano H (2006) Transgenic tobacco plants producing caffeine: a potential new strategy for insect pest control. Transgenic Res 15:667
Kim YS, Sano H (2008) Pathogen resistance of transgenic tobacco plants producing caffeine. Phytochemistry 69:882
Kim YS, Choi YE, Sano H (2010) Plant vaccination: stimulation of defense system by caffeine production in planta. Plant Signal Behav 5:489
Crozier TWM, Stalmach A, Lean MEJ, Crozier A (2012) Espresso coffees, caffeine and chlorogenic acid intake: potential health implications. Food Funct 3:30
Crozier A, Ashihara H (2006) The cup that cheers. Caffeine biosynthesis: biochemistry and molecular biology. Biochemist 28(5):23
Ogita S, Uefuji H, Yamaguchi Y, Nozomu K, Sano H (2003) Producing decaffeinated coffee plants. Nature 423:823
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 54:931
Ogita S, Uefuji H, Morimoto M, Sano H (2005) Metabolic engineering of caffeine production. Plant Biotechnol 22:461
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 163
Mohanpuria P, Kumar V, Ahuja P, Yadav S (2011) Producing low-caffeine tea through post-transcriptional silencing of caffeine synthase mRNA. Plant Mol Biol 76:523
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 67:882
Mohanpuria P, Kumar V, Yadav S (2010) Tea caffeine: metabolism, functions, and reduction strategies. Food Sci Biotechnol 19:275
Nakayama F, Mizuno K, Kato M (2015) Biosynthesis of caffeine underlying the diversity of motif B′ methyltransferase. Nat Prod Commun 10:799
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.
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Ashihara, H., Mizuno, K., Yokota, T., Crozier, A. (2017). Xanthine Alkaloids: Occurrence, Biosynthesis, and Function in Plants. In: Kinghorn, A., Falk, H., Gibbons, S., Kobayashi, J. (eds) Progress in the Chemistry of Organic Natural Products 105. Progress in the Chemistry of Organic Natural Products, vol 105. Springer, Cham. https://doi.org/10.1007/978-3-319-49712-9_1
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