Skip to main content
SpringerLink
Log in

Distribution, Biosynthesis and Catabolism of Methylxanthines in Plants

  • Chapter
  • First Online:
Methylxanthines

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 200))

Abstract

Methylxanthines and methyluric acids are purine alkaloids that are synthesized in quantity in a limited number of plant species, including tea, coffee and cacao. This review summarizes the pathways, enzymes and related genes of caffeine biosynthesis. The main biosynthetic pathway is a sequence consisting of xanthosine → 7-methylxanthosine → 7-methylxanthine → theobromine → caffeine. Catabolism of caffeine starts with its conversion to theophylline. Typically, this reaction is very slow in caffeine-accumulating plants. Finally, the ecological roles of caffeine and the production of decaffeinated coffee plants are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 349.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anaya AL, Cruz-Ortega R, Waller GR (2006) Metabolism and ecology of purine alkaloids. Front Biosci 11:2354–2370

    Article  PubMed  CAS  Google Scholar 

  • Ashihara H, Crozier A (1999a) Biosynthesis and metabolism of caffeine and related purine alkaloids in plants. Adv Bot Res 30:117–205

    Article  CAS  Google Scholar 

  • Ashihara H, Crozier A (1999b) Biosynthesis and catabolism of caffeine in low-caffeine-containing species of Coffea. J Agric Food Chem 47:3425–3431

    Article  PubMed  CAS  Google Scholar 

  • Ashihara H, Kubota H (1986) Patterns of adenine metabolism and caffeine biosynthesis in different parts of tea seedlings. Physiol Plant 68:275–281

    Google Scholar 

  • Ashihara H, Suzuki T (2004) Distribution and biosynthesis of caffeine in plants. Front Biosci 9:1864–1876

    Article  PubMed  CAS  Google Scholar 

  • Ashihara H, Gillies FM, Crozier A (1997) Metabolism of caffeine and related purine alkaloids in leaves of tea (Camellia sinensis L.). Plant Cell Physiol 38:413–419

    Article  CAS  Google Scholar 

  • Ashihara H, Kato M, Ye C-X (1998) Biosynthesis and metabolism of purine alkaloids in leaves of cocoa tea (Camellia ptilophylla). J Plant Res 111:599–604

    Article  CAS  Google Scholar 

  • 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 198:334–339

    Article  CAS  Google Scholar 

  • Ashihara H, Sano H, Crozier A (2008) Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69:841–856

    Article  PubMed  CAS  Google Scholar 

  • Baumann TW, Oechslin M, Wanner H (1976) Caffeine and methylated uric acids: chemical patterns during vegetative development of Coffea liberica. Biochem Physiol Pflanz 170:217–225

    CAS  Google Scholar 

  • Baumann TW, Wanner H (1980) The 1,3,7,9-tetramethyluric acid content of cupu (Theobroma grandiflorum). Acta Amaz 10:425

    CAS  Google Scholar 

  • Baumann TW, Schulthess BH, Hanni K (1995) Guarana (Paulinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 39:1063–1070

    Article  CAS  Google Scholar 

  • Campa C, Doulbeau S, Dussert S, Hamon S, Noirot M (2005) Diversity in bean caffeine content among wild Coffea species: evidence of a discontinuous distribution. Food Chem 91:633–637

    Article  CAS  Google Scholar 

  • Charrier A, Berthaud J (1975) Variation de la teneur en cafeine dans le genre Coffea. Cafe Cacao The 19:251–264

    CAS  Google Scholar 

  • D’Auria JC, Chen F, Pichersky E (2003) The SABATH family of MTs in Arabidopsis thaliana and other plant species. In: Romeo JT (ed) Recent advances in phytochemistry, vol 37. Elsevier, Oxford, pp 253–283

    Google Scholar 

  • Deng WW, Li Y, Ogita S, Ashihara H (2008) Fine control of caffeine biosynthesis in tissue cultures of Camellia sinensis. Phytochem Lett 1:195–198

    Article  CAS  Google Scholar 

  • 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 12:949–961

    PubMed  CAS  Google Scholar 

  • Duthie GG, Crozier A (2003) Beverages. In: Goldberg G (ed) Plants: diet and health. British Nutrition Foundation/ Chapman and Hall, London, pp 147–182

    Chapter  Google Scholar 

  • Eteng MU, Eyong EU, Akpanyung EO, Agiang MA, Aremu CY (1997) Recent advances in caffeine and theobromine toxicities: a review. Plant Food Hum Nutr 51:231–243

    Article  CAS  Google Scholar 

  • Gluck M, Lingens F (1988) Heteroxanthine demethylase, a new enzyme in the degradation of caffeine by Pseudomonas putida. Appl Microbiol Biotechnol 28:59–62

    Article  Google Scholar 

  • Hammerstone JF, Romanczyk LJ, Aitken WM (1994) Purine alkaloid distribution within Herrania and Theobroma. Phytochemistry 35:1237–1240

    Article  CAS  Google Scholar 

  • Heilmann W (2001) Technology II: decaffeination of coffee. In: Clarke RJ, Vitzthum OG (eds) Coffee: recent developments. Blackwell, Oxford, pp 108–124

    Google Scholar 

  • Hohnloser W, Osswald B, Lingens F (1980) Enzymological aspects of caffeine demethylation and formaldehyde oxidation by Pseudomonas putida C1. Hoppe Seylers Z Physiol Chem 361:1763–1766

    Article  PubMed  CAS  Google Scholar 

  • Hollingsworth RG, Armstrong JW, Campbell E (2003) Pest control: caffeine as a repellent for slugs and snails. Nature 417:915–916

    Article  Google Scholar 

  • Huber M, Baumann TW (1998) The first step of caffeine degradation in coffee – still a mystery. In: Symposium future trends in phytochemistry. The Phytochemical Society of Europe, Rolduc

    Google Scholar 

  • 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 229:559–568

    Article  PubMed  CAS  Google Scholar 

  • Ito E, Ashihara H (1999) Contribution of purine nucleotide biosynthesis de novo to the formation of caffeine in young tea (Camellia sinencis) leaves. J Plant Physiol 254:145–151

    Article  Google Scholar 

  • Ito E, Crozier A, Ashihara H (1997) Theophylline metabolism in higher plants. Biochim Biophys Acta 1336:323–330

    Article  PubMed  CAS  Google Scholar 

  • Joshi CP, Chiang VL (1998) Conserved sequence motifs in plant S-adenosyl-l-methionine-dependent methyltransferases. Plant Mol Biol 37:663–674

    Article  PubMed  CAS  Google Scholar 

  • Kato M, Mizuno K, Crozier A, Fujimura T, Ashihara H (2000) A gene encoding caffeine synthase from tea leaves. Nature 406:956–957

    Article  PubMed  CAS  Google Scholar 

  • 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 120:579–586

    Article  PubMed  CAS  Google Scholar 

  • Kato M, Mizuno K (2004) Caffeine synthase and related methyltransferases in plants. Front Biosci 9:1833–1842

    Article  CAS  Google Scholar 

  • Keya CA, Crozier A, Ashihara H (2003) Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin. FEBS Lett 554:473–477

    Article  PubMed  CAS  Google Scholar 

  • Kim YS, Uefuji H, Ogita S, Sano H (2006) Transgenic tobacco plants producing caffeine: a potential new strategy for insect pest control. Transgenic Res 15:667–672

    Article  PubMed  CAS  Google Scholar 

  • 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 499:50–54

    Article  PubMed  CAS  Google Scholar 

  • 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 171:242–250

    Google Scholar 

  • 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 41:977–984

    Article  CAS  Google Scholar 

  • Kretschmar JA, Baumann TW (1999) Caffeine in Citrus flowers. Phytochemistry 52:19–23

    Article  CAS  Google Scholar 

  • Li Y, Ogita S, Keya CA, Ashihara H (2008) Expression of caffeine biosynthesis gene in tea (Camellia sinensis). Z Naturforsch 63c:267–270

    Google Scholar 

  • Mazzafera P (2004) Catabolism of caffeine in plants and microorganisms. Front Biosci 9:1348–1359

    Article  PubMed  CAS  Google Scholar 

  • Mazzafera P, Carvalho A (1992) Breeding for low seed caffeine content of coffee (Coffea L.) by interspecific hybridization. Euphytica 59:55–60

    Google Scholar 

  • McCarthy AA, McCarthy JG (2007) The structure of two N-methyltransferases from the caffeine biosynthetic pathway. Plant Physiol 144:879–889

    Article  PubMed  CAS  Google Scholar 

  • Mizuno K, Tanaka H, Kato M, Ashihara H, Fujimura T (2001) cDNA cloning of caffeine (theobromine) synthase from coffee (Coffea arabica L). In: International scientific colloquium on coffee 19. ASIC, Paris, pp 815–818

    Google Scholar 

  • Mizuno K, Kato M, Irino F, Yoneyama N, Fujimura T, Ashihara H (2003a) The first committed step reaction of caffeine biosynthesis: 7-methylxanthosine synthase is closely homologous to caffeine synthases in coffee (Coffea arabica L.). FEBS Lett 547:56–60

    Article  PubMed  CAS  Google Scholar 

  • Mizuno K, Okuda A, Kato M, Yoneyama N, Tanaka H, Ashihara H, Fujimura T (2003b) 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 534:75–81

    Article  PubMed  CAS  Google Scholar 

  • Moffatt BA, Ashihara H (2002) Purine and pyrimidine nucleotide synthesis and metabolism. The Arabidopsis book. American Society of Plant Biologists, Rockville. doi:10.1199/tab.0018, http://www.aspb.org/publications/arabidopsis/

  • Murata J, Roepke J, Gordon H, Luca VD (2008) The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell 20:524–542

    Article  PubMed  CAS  Google Scholar 

  • Nagai C, Rakotomalala JJ, Katahira R, Li Y, Yamagata K, Ashihara H (2008) Production of a new low-caffeine hybrid coffee and the biochemical mechanism of low caffeine accumulation. Euphytica 164:133–142

    Article  CAS  Google Scholar 

  • Nagata T, Sakai S (1985) Purine base pattern of Camellia irrawadiensis. Phytochemistry 24:2271–2272

    Article  CAS  Google Scholar 

  • Negishi O, Ozawa T, Imagawa H (1988) N-Methylnucleosidase from tea leaves. Agric Biol Chem 52:169–175

    Article  CAS  Google Scholar 

  • Negishi O, Ozawa T, Imagawa H (1994) Guanosine deaminase and guanine deaminase from tea leaves. Biosci Biotechnol Biochem 58:1277–1281

    Article  CAS  Google Scholar 

  • 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 276:8213–8218

    Google Scholar 

  • 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 54:931–941

    Article  PubMed  CAS  Google Scholar 

  • Ogita S, Uefuji H, Yamaguchi Y, Nozomu K, Sano H (2003) Producing decaffeinated coffee plants. Nature 423:823

    Article  PubMed  CAS  Google Scholar 

  • Petermann J, Baumann TW (1983) Metabolic relations between methylxanthines and methyluric acids in Coffea. Plant Physiol 73:961–964

    Article  PubMed  CAS  Google Scholar 

  • Rakotomalala JJ, Cros E, Clifford MN, Charrier A (1992) Caffeine and theobromine in green beans from Mascarocoffea. Phytochemistry 31:1271–1272

    Article  CAS  Google Scholar 

  • Ross JR, Nam KH, D’Auria JC, Pichersky E (1999) S-Adenosyl-l-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 367:9–16

    Article  PubMed  CAS  Google Scholar 

  • Scheline RR (1991) Handbook of mammalian metabolism of plant compounds. CRC, Boca Raton

    Google Scholar 

  • Senanayake UM, Wijesekera ROB (1971) Theobromine and caffeine content of the cocoa bean during its growth. J Sci Food Agric 22:262–263

    Article  CAS  Google Scholar 

  • Silvarolla MB, Mazzafera P, Fazuoli LC (2004) A naturally decaffeinated arabica coffee. Nature 429:826

    Article  PubMed  CAS  Google Scholar 

  • Seo HS, Song JT, Lee YH, Iwang I, Lee JS, Choi YD (2001) Jasmonic acid carboxyl methyltransferase: a key enzyme for jasmonate-regulated plant responses. Proc Natl Aacd Sci USA 98:4788–4793

    Article  CAS  Google Scholar 

  • Stasolla C, Katahira R, Thorpe TA, Ashihara H (2003) Purine and pyrimidine nucleotide metabolism in higher plants. J Plant Physiol 160:1271–1295

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Waller GR (1984) Biodegradation of caffeine: formation of theophylline and caffeine in mature Coffea arabica fruits. J Sci Food Agric 35:66–70

    Article  CAS  Google Scholar 

  • Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucl Acids Res 22:4673–4680

    Google Scholar 

  • 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-methyltrasferases and its potential as a pest repellant. Plant Mol Biol 59:221–227

    Article  PubMed  CAS  Google Scholar 

  • 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 132:372–380

    Article  PubMed  CAS  Google Scholar 

  • 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 19:32–45

    Article  PubMed  CAS  Google Scholar 

  • Vitzthum OG (2005) Decaffeination. In: Illy A, Viani R (eds) Espresso coffee: the science of quality, 2nd edn. Elsevier, Amsterdam, pp 142–147

    Google Scholar 

  • Weckerle CS, Stutz MA, Baumann TW (2003) Purine alkaloids in Paullinia. Phytochemistry 64:735–742

    Article  PubMed  CAS  Google Scholar 

  • 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 448:123–132

    Article  PubMed  CAS  Google Scholar 

  • Ye C, Un Y, Zhou H, Cheng F, Li X (1997) Isolation and analysis of purine alkaloids from Camellia ptilophylla Chang. Acta Sci Nat Univ Sunyatseni 36:30–33

    CAS  Google Scholar 

  • 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 275:125–135

    Article  PubMed  CAS  Google Scholar 

  • 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 146:455–467

    Article  PubMed  CAS  Google Scholar 

  • Zheng XQ, Ashihara H (2004) Distribution, biosynthesis and function of purine and pyridine alkaloids in Coffea arabica seedlings. Plant Sci 166:807–813

    Article  CAS  Google Scholar 

  • 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 60:129–134

    Article  PubMed  CAS  Google Scholar 

  • Zheng XQ, Koyama Y, Nagai C, Ashihara H (2004) Biosynthesis, accumulation and degradation of theobromine in developing Theobroma cacao fruits. J Plant Physiol 161:363–369

    Article  PubMed  CAS  Google Scholar 

  • 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 15:1704–1716

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, 112-8610, Japan

    Hiroshi Ashihara & Misako Kato

  2. Plant Products and Human Nutrition Group, Division of Developmental Medicine, Faculty of Medicine, University of Glasgow, Graham Kerr Building, Glasgow, G12 8QQ, UK

    Alan Crozier

Authors
  1. Hiroshi Ashihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Misako Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan Crozier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Ashihara .

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Ashihara, H., Kato, M., Crozier, A. (2011). Distribution, Biosynthesis and Catabolism of Methylxanthines in Plants. In: Methylxanthines. Handbook of Experimental Pharmacology, vol 200. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13443-2_2

Download citation

Publish with us

Policies and ethics

Search

Navigation