The triterpenes are one of the most numerous and diverse groups of plant natural products. They are complex molecules that are, for the most part, beyond the reach of chemical synthesis. Simple triterpenes are components of surface waxes and specialized membranes and may potentially act as signaling molecules, whereas complex glycosylated triterpenes (saponins) provide protection against pathogens and pests. Simple and conjugated triterpenes have a wide range of applications in the food, health, and industrial biotechnology sectors. Here, we review recent developments in the field of triterpene biosynthesis, give an overview of the genes and enzymes that have been identified to date, and discuss strategies for discovering new triterpene biosynthetic pathways.


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Literature Cited

  1. Abe I. 1.  2007. Enzymatic synthesis of cyclic triterpenes. Nat. Prod. Rep. 24:1311–31 [Google Scholar]
  2. Abe I, Sakano Y, Sodeyama M, Tanaka H, Noguchi H. 2.  et al. 2004. Mechanism and stereochemistry of enzymatic cyclization of 24,30-bisnor-2,3-oxidosqualene by recombinant β-amyrin synthase. J. Am. Chem. Soc. 126:6880–81 [Google Scholar]
  3. Abe I, Sakano Y, Tanaka H, Lou W, Noguchi H. 3.  et al. 2004. Enzymatic cyclization of 22,23-dihydro-2,3-oxidosqualene into euph-7-en-3β-ol and bacchar-12-en-3β-ol by recombinant β-amyrin synthase. J. Am. Chem. Soc. 126:3426–27 [Google Scholar]
  4. Achnine L, Huhman DV, Farag MA, Sumner LW, Blount JW, Dixon RA. 4.  2005. Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. Plant J. 41:875–87 [Google Scholar]
  5. Augustin JM, Drok S, Shinoda T, Sanmiya K, Nielsen JK. 5.  et al. 2012. UDP-glycosyltransferases from the UGT73C subfamily in Barbarea vulgaris catalyze sapogenin 3-O-glucosylation in saponin-mediated insect resistance. Plant Physiol. 160:1881–95 [Google Scholar]
  6. Augustin JM, Kuzina V, Andersen SB, Bak S. 6.  2011. Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry 72:435–57 [Google Scholar]
  7. Basyuni M, Oku H, Inafuku M, Baba S, Iwasaki H. 7.  et al. 2006. Molecular cloning and functional expression of a multifunctional triterpene synthase cDNA from a mangrove species Kandelia candel (L.) Druce. Phytochemistry 67:2517–24 [Google Scholar]
  8. Basyuni M, Oku H, Tsujimoto E, Kinjo K, Baba S, Takara K. 8.  2007. Triterpene synthases from the Okinawan mangrove tribe, Rhizophoraceae. FEBS J. 274:5028–42 [Google Scholar]
  9. Bode HB, Zeggel B, Silakowski B, Wenzel SC, Reichenbach H. 9.  et al. 2003. Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca. Mol. Microbiol. 47:471–81 [Google Scholar]
  10. Bowles D, Lim EK, Poppenberger B, Vaistij FE. 10.  2006. Glycosyltransferases of lipophilic small molecules. Annu. Rev. Plant Biol. 57:567–97 [Google Scholar]
  11. Brendolise C, Yauk Y-K, Eberhard ED, Wang M, Chagne D. 11.  et al. 2011. An unusual plant triterpene synthase with predominant α-amyrin-producing activity identified by characterizing oxidosqualene cyclases from Malus × domestica. FEBS J. 278:2485–99 [Google Scholar]
  12. Buschhaus C, Herz H, Jetter R. 12.  2007. Chemical composition of the epicuticular and intracuticular wax layers on the adaxial side of Ligustrum vulgare leaves. New Phytol. 176:311–16 [Google Scholar]
  13. Buschhaus C, Jetter R. 13.  2012. Composition and physiological function of the wax layers coating Arabidopsis leaves: β-Amyrin negatively affects the intracuticular water barrier. Plant Physiol. 160:1120–29 [Google Scholar]
  14. Cammareri M, Consiglio MF, Pecchia P, Corea G, Lanzotti V. 14.  et al. 2008. Molecular characterization of β-amyrin synthase from Aster sedifolius L. and triterpenoid saponin analysis. Plant Sci. 175:255–61 [Google Scholar]
  15. Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B. 15.  2009. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res. 37:Suppl. 1D233–38 [Google Scholar]
  16. Cao R, Zhang Y, Mann FM, Huang C, Mukkamala D. 16.  et al. 2010. Diterpene synthases and the nature of the isoprene fold. Proteins 78:2417–32 [Google Scholar]
  17. Caputi L, Malnoy M, Goremykin V, Nikiforova S, Martens S. 17.  2012. A genome-wide phylogenetic reconstruction of family 1 UDP-glycosyltransferases revealed the expansion of the family during the adaptation of plants to life on land. Plant J. 69:1030–42 [Google Scholar]
  18. Carelli M, Biazzi E, Panara F, Tava A, Scaramelli L. 18.  et al. 2011. Medicago truncatula CYP716A12 is a multifunctional oxidase involved in the biosynthesis of hemolytic saponins. Plant Cell 23:3070–81 [Google Scholar]
  19. Cartwright AM, Lim EK, Kleanthous C, Bowles DJ. 19.  2008. A kinetic analysis of regiospecific glucosylation by two glycosyltransferases of Arabidopsis thaliana: domain swapping to introduce new activities. J. Biol. Chem. 283:15724–31 [Google Scholar]
  20. Castillo DA, Kolesnikova MD, Matsuda SPT. 20.  2013. An effective strategy for exploring unknown metabolic pathways by genome mining. J. Am. Chem. Soc. 135:5885–94 [Google Scholar]
  21. Chappell J. 21.  2002. The genetics and molecular genetics of terpene and sterol origami. Curr. Opin. Plant Biol. 5:151–57 [Google Scholar]
  22. Corey EJ, Matsuda SP, Bartel B. 22.  1993. Isolation of an Arabidopsis thaliana gene encoding cycloartenol synthase by functional expression in a yeast mutant lacking lanosterol synthase by the use of a chromatographic screen. Proc. Natl. Acad. Sci. USA 90:11628–32 [Google Scholar]
  23. Delis C, Krokida A, Georgiou S, Peña-Rodríguez LM, Kavroulakis N. 23.  et al. 2011. Role of lupeol synthase in Lotus japonicus nodule formation. New Phytol. 189:335–46 [Google Scholar]
  24. Domingo V, Arteaga JF, Quílez del Moral JF, Barrero AF. 24.  2009. Unusually cyclized triterpenes: occurrence, biosynthesis and chemical synthesis. Nat. Prod. Rep. 26:115–34 [Google Scholar]
  25. Ebizuka Y, Katsube Y, Tsutsumi T, Kushiro T, Shibuya M. 25.  2003. Functional genomics approach to the study of triterpene biosynthesis. Pure Appl. Chem. 75:369–74 [Google Scholar]
  26. Eschenmoser A, Arigoni D. 26.  2005. Revisited after 50 years: the “stereochemical interpretation of the biogenetic isoprene rule for the triterpenes.”. Helv. Chim. Acta 88:3011–50 [Google Scholar]
  27. Fazio GC, Xu R, Matsuda SP. 27.  2004. Genome mining to identify new plant triterpenoids. J. Am. Chem. Soc. 126:5678–79 [Google Scholar]
  28. Field B, Fiston-Lavier A-S, Kemen A, Geisler K, Quesneville H, Osbourn AE. 28.  2011. Formation of plant metabolic gene clusters within dynamic chromosomal regions. Proc. Natl. Acad. Sci. USA 108:16116–21 [Google Scholar]
  29. Field B, Osbourn AE. 29.  2008. Metabolic diversification—independent assembly of operon-like gene clusters in different plants. Science 320:543–47 [Google Scholar]
  30. Fukushima EO, Seki H, Ohyama K, Ono E, Umemoto N. 30.  et al. 2011. CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis. Plant Cell Physiol. 52:2050–61 [Google Scholar]
  31. Fukushima EO, Seki H, Sawai S, Suzuki M, Ohyama K. 31.  et al. 2013. Combinatorial biosynthesis of legume natural and rare triterpenoids in engineered yeast. Plant Cell Physiol. 54:740–49 [Google Scholar]
  32. Geisler K, Hughes RK, Sainsbury F, Lomonossoff GP, Rejzek M. 32.  et al. 2013. Biochemical analysis of a multi-functional cytochrome P450 (CYP51) enzyme required for synthesis of antimicrobial triterpenes in plants. Proc. Natl. Acad. Sci. USA 110:E3360–67 [Google Scholar]
  33. Go YS, Lee SB, Kim HJ, Kim J, Park H-Y. 33.  et al. 2012. Identification of marneral synthase, which is critical for growth and development in Arabidopsis. Plant J. 72:791–804 [Google Scholar]
  34. Godzina SM, Lovato MA, Meyer MM, Foster KA, Wilson WK. 34.  et al. 2000. Cloning and characterization of the Dictyostelium discoideum cycloartenol synthase cDNA. Lipids 35:249–55 [Google Scholar]
  35. Guhling O, Hobl B, Yeats T, Jetter R. 35.  2006. Cloning and characterization of a lupeol synthase involved in the synthesis of epicuticular wax crystals on stem and hypocotyl surfaces of Ricinus communis. Arch. Biochem. Biophys. 448:60–72 [Google Scholar]
  36. Hamberger B, Bak S. 36.  2013. Plant P450s as drivers for evolution of species-specific chemical diversity. Philos. Trans. R. Soc. B 368:20120426 [Google Scholar]
  37. Han JY, Hwang HS, Choi SW, Kim HJ, Choi YE. 37.  2012. Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol. 53:1535–45 [Google Scholar]
  38. Han JY, Kim HJ, Kwon YS, Choi YE. 38.  2011. The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol. 52:2062–73 [Google Scholar]
  39. Hansen KS, Kristensen C, Tattersall DB, Jones PR, Olsen CE. 39.  et al. 2003. The in vitro substrate regiospecificity of recombinant UGT85B1, the cyanohydrin glucosyltransferase from Sorghum bicolor. Phytochemistry 64:143–51 [Google Scholar]
  40. Haralampidis K, Bryan G, Qi X, Papadopoulou K, Bakht S. 40.  et al. 2001. A new class of oxidosqualene cyclases directs synthesis of antimicrobial phytoprotectants in monocots. Proc. Natl. Acad. Sci. USA 98:13431–36 [Google Scholar]
  41. Hartmann K, Peiter E, Koch K, Schubert S, Schreiber L. 41.  2002. Chemical composition and ultrastructure of broad bean (Vicia faba L.) nodule endodermis in comparison to the root endodermis. Planta 215:14–25 [Google Scholar]
  42. Hayashi H, Hiraoka N, Ikeshiro Y, Yazaki K, Tanaka S. 42.  et al. 1999. Molecular cloning of a cDNA encoding cycloartenol synthase from Luffa cylindrica. Plant Physiol. 121:1384 [Google Scholar]
  43. Hayashi H, Huang P, Inoue K, Hiraoka N, Ikeshiro Y. 43.  et al. 2001. Molecular cloning and characterization of isomultiflorenol synthase, a new triterpene synthase from Luffa cylindrica, involved in biosynthesis of bryonolic acid. Eur. J. Biochem. 268:6311–17 [Google Scholar]
  44. Hayashi H, Huang P, Kirakosyan A, Inoue K, Hiraoka N. 44.  et al. 2001. Cloning and characterization of a cDNA encoding β-amyrin synthase involved in glycyrrhizin and soyasaponin biosyntheses in licorice. Biol. Pharm. Bull. 24:912–16 [Google Scholar]
  45. Hayashi H, Huang P, Takada S, Obinata M, Inoue K. 45.  et al. 2004. Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza glabra. Biol. Pharm. Bull. 27:1086–92 [Google Scholar]
  46. Herrera JBR, Bartel B, Wilson WK, Matsuda SPT. 46.  1998. Cloning and characterization of the Arabidopsis thaliana lupeol synthase gene. Phytochemistry 49:1905–11 [Google Scholar]
  47. Hill RA, Connolly JD. 47.  2012. Triterpenoids. Nat. Prod. Rep. 29:780–818 [Google Scholar]
  48. Hruz T, Laule O, Szabo G, Wessendorp F, Bleuler S. 48.  et al. 2008. Genevestigator V3: a reference expression database for the meta-analysis of transcriptomes. Adv. Bioinforma. 2008:420747 [Google Scholar]
  49. Huang L, Li J, Ye H, Li C, Wang H. 49.  et al. 2012. Molecular characterization of the pentacyclic triterpenoid biosynthetic pathway in Catharanthus roseus. Planta 236:1571–81 [Google Scholar]
  50. Huang S, Li R, Zhang Z, Li L, Gu X. 50.  et al. 2009. The genome of the cucumber, Cucumis sativus L. Nat. Genet. 41:1275–81 [Google Scholar]
  51. Husar S, Berthiller F, Fujioka S, Rozhon W, Khan M. 51.  et al. 2011. Overexpression of the UGT73C6 alters brassinosteroid glucoside formation in Arabidopsis thaliana. BMC Plant Biol. 11:51 [Google Scholar]
  52. Husselstein-Muller T, Schaller H, Benveniste P. 52.  2001. Molecular cloning and expression in yeast of 2,3-oxidosqualene-triterpenoid cyclases from Arabidopsis thaliana. Plant Mol. Biol. 45:75–92 [Google Scholar]
  53. Inagaki Y-S, Etherington G, Geisler K, Field B, Dokarry M. 53.  et al. 2011. Investigation of the potential for triterpene synthesis in rice through genome mining and metabolic engineering. New Phytol. 191:432–48 [Google Scholar]
  54. Itkin M, Heinig U, Tzfadia O, Bhide AJ, Shinde S. 54.  et al. 2013. Biosynthesis of antinutritional alkaloids in solanaceous crops is mediated by clustered genes. Science 341:175–79 [Google Scholar]
  55. Itkin M, Rogachev I, Alkan N, Rosenberg T, Malitsky S. 55.  et al. 2011. GLYCOALKALOID METABOLISM1 is required for steroidal alkaloid glycosylation and prevention of phytotoxicity in tomato. Plant Cell 23:4507–25 [Google Scholar]
  56. Ito R, Mori K, Hashimoto I, Nakano C, Sato T, Hoshino T. 56.  2011. Triterpene cyclases from Oryza sativa L.: cycloartenol, parkeol and achilleol B synthases. Org. Lett. 13:2678–81 [Google Scholar]
  57. Iturbe-Ormaetxe I, Haralampidis K, Papadopoulou K, Osbourn AE. 57.  2003. Molecular cloning and characterization of triterpene synthases from Medicago truncatula and Lotus japonicus. Plant Mol. Biol. 51:731–43 [Google Scholar]
  58. Jetter R, Sodhi R. 58.  2011. Chemical composition and microstructure of waxy plant surfaces: triterpenoids and fatty acid derivatives on leaves of Kalanchoe daigremontiana. Surf. Interface Anal. 43:326–30 [Google Scholar]
  59. Jones DT, Taylor WR, Thornton JM. 59.  1992. The rapid generation of mutation data matrices from protein sequences. Comput. Appl. Biosci. 8:275–82 [Google Scholar]
  60. Kajikawa M, Yamato KT, Fukuzawa H, Sakai Y, Uchida H, Ohyama K. 60.  2005. Cloning and characterization of a cDNA encoding β-amyrin synthase from petroleum plant Euphorbia tirucalli L. Phytochemistry 66:1759–66 [Google Scholar]
  61. Kawano N, Ichinose K, Ebizuka Y. 61.  2002. Molecular cloning and functional expression of cDNAs encoding oxidosqualene cyclases from Costus speciosus. Biol. Pharm. Bull. 25:477–82 [Google Scholar]
  62. Kirby J, Romanini DW, Paradise EM, Keasling JD. 62.  2008. Engineering triterpene production in Saccharomyces cerevisiae β-amyrin synthase from Artemisia annua. FEBS J. 275:1852–59 [Google Scholar]
  63. Kliebenstein DJ, Osbourn A. 63.  2012. Making new molecules—evolution of pathways for novel metabolites in plants. Curr. Opin. Plant Biol. 15:415–23 [Google Scholar]
  64. Kohara A, Nakajima C, Hashimoto K, Ikenaga T, Tanaka H. 64.  et al. 2005. A novel glucosyltransferase involved in steroid saponin biosynthesis in Solanum aculeatissimum. Plant Mol. Biol. 57:225–39 [Google Scholar]
  65. Kohara A, Nakajima C, Yoshida S, Muranaka T. 65.  2007. Characterization and engineering of glycosyltransferases responsible for steroid saponin biosynthesis in solanaceous plants. Phytochemistry 68:478–86 [Google Scholar]
  66. Kolesnikova MD, Obermeyer AC, Wilson WK, Lynch DA, Xiong Q, Matsuda SPT. 66.  2007. Stereochemistry of water addition in triterpene synthesis: the structure of arabidiol. Org. Lett. 9:2183–86 [Google Scholar]
  67. Kolesnikova MD, Wilson WK, Lynch DA, Obermeyer AC, Matsuda SP. 67.  2007. Arabidopsis camelliol C synthase evolved from enzymes that make pentacycles. Org. Lett. 9:5223–26 [Google Scholar]
  68. Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT. 68.  2006. Lanosterol biosynthesis in plants. Arch. Biochem. Biophys. 447:87–95 [Google Scholar]
  69. Krokida A, Delis C, Geisler K, Garagounis C, Tsikou D. 69.  et al. 2013. A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis. New Phytol. 200:675–90 [Google Scholar]
  70. Kunii M, Kitahama Y, Fukushima EO, Seki H, Muranaka T. 70.  et al. 2012. β-Amyrin oxidation by oat CYP51H10 expressed heterologously in yeast cells: the first example of CYP51-dependent metabolism other than the 14-demethylation of sterol precursors. Biol. Pharm. Bull. 35:801–4 [Google Scholar]
  71. Kushiro T, Shibuya M, Ebizuka Y. 71.  1998. β-Amyrin synthase: cloning of the oxidosqualene cyclase that catalyzes the formation of the most popular triterpene among higher plants. Eur. J. Biochem. 256:238–44 [Google Scholar]
  72. Kushiro T, Shibuya M, Masuda K, Ebizuka Y. 72.  2000. Mutational studies on triterpene synthases: engineering lupeol synthase into β-amyrin synthase. J. Am. Chem. Soc. 122:6816–24 [Google Scholar]
  73. Kushiro T, Shibuya M, Masuda K, Ebizuka Y. 73.  2000. A novel multifunctional triterpene synthase from Arabidopsis thaliana. Tetrahedron Lett. 41:7705–10 [Google Scholar]
  74. Kuzina V, Ekstrøm CT, Andersen SB, Nielsen JK, Olsen CE. 74.  et al. 2009. Identification of defense compounds in Barbarea vulgaris against the herbivore Phyllotreta nemorum by an ecometabolomic approach. Plant Physiol. 151:1077–90 [Google Scholar]
  75. Lamb DC, Jackson CJ, Warrilow AGS, Manning NJ, Kelly DE, Kelly SL. 75.  2007. Lanosterol biosynthesis in the prokaryote Methylococcus capsulatus: insight into the evolution of sterol biosynthesis. Mol. Biol. Evol. 24:1714–21 [Google Scholar]
  76. Lodeiro S, Schulz-Gasch T, Matsuda SPT. 76.  2005. Enzyme redesign: two mutations cooperate to convert cycloartenol synthase into an accurate lanosterol synthase. J. Am. Chem. Soc. 127:14132–33 [Google Scholar]
  77. Lodeiro S, Xiong Q, Wilson WK, Kolesnikova MD, Onak CS, Matsuda SPT. 77.  2007. An oxidosqualene cyclase makes numerous products by diverse mechanisms: a challenge to prevailing concepts of triterpene biosynthesis. J. Am. Chem. Soc. 129:11213–22 [Google Scholar]
  78. Markstadter C, Federle W, Jetter R, Riederer M, Holldobler B. 78.  2000. Chemical composition of the slippery epicuticular wax blooms on Macaranga (Euphorbiaceae) ant-plants. Chemoecology 10:33–40 [Google Scholar]
  79. Meesapyodsuk D, Balsevich J, Reed DW, Covello PS. 79.  2007. Saponin biosynthesis in Saponaria vaccaria. cDNAs encoding β-amyrin synthase and a triterpene carboxylic acid glucosyltransferase. Plant Physiol. 143:959–69 [Google Scholar]
  80. Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ. 80.  et al. 2007. The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318:245–50 [Google Scholar]
  81. Milkowski C, Strack D. 81.  2004. Serine carboxypeptidase-like acyltransferases. Phytochemical 65:517–24 [Google Scholar]
  82. Mizutani M. 82.  2012. The 50th anniversary and new horizons of cytochrome P450 research: expanding knowledge on the multiplicity and versatility of P450 and its industrial applications. Biol. Pharm. Bull. 35:824–32 [Google Scholar]
  83. Moehs CP, Allen PV, Friedman M, Belknap WR. 83.  1997. Cloning and expression of solanidine UDP-glucose glucosyltransferase from potato. Plant J. 11:227–36 [Google Scholar]
  84. Morikubo N, Fukuda Y, Ohtake K, Shinya N, Kiga D. 84.  et al. 2006. Cation-π interaction in the polyolefin cyclization cascade uncovered by incorporating unnatural amino acids into the catalytic sites of squalene cyclase. J. Am. Chem. Soc. 128:13184–94 [Google Scholar]
  85. Morita M, Shibuya M, Kushiro T, Masuda K, Ebizuka Y. 85.  2000. Molecular cloning and functional expression of triterpene synthases from pea (Pisum sativum): new α-amyrin-producing enzyme is a multifunctional triterpene synthase. Eur. J. Biochem. 267:3453–60 [Google Scholar]
  86. Morita M, Shibuya M, Lee MS, Sankawa U, Ebizuka Y. 86.  1997. Molecular cloning of pea cDNA encoding cycloartenol synthase and its functional expression in yeast. Biol. Pharm. Bull. 20:770–75 [Google Scholar]
  87. Morlacchi P, Wilson WK, Xiong Q, Bhaduri A, Sttivend D. 87.  et al. 2009. Product profile of PEN3: the last unexamined oxidosqualene cyclase in Arabidopsis thaliana. Org. Lett. 11:2627–30 [Google Scholar]
  88. Moses T, Pollier J, Thevelein JM, Goossens A. 88.  2013. Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro. New Phytol. 200:27–43 [Google Scholar]
  89. Mugford ST, Louveau T, Melton R, Qi X, Bakht S. 89.  et al. 2013. Modularity of plant metabolic gene clusters: a trio of linked genes that are collectively required for acylation of triterpenes in oat. Plant Cell 25:1078–92 [Google Scholar]
  90. Mugford ST, Milkowski C. 90.  2012. Serine carboxypeptidase-like acyltransferases from plants. Methods Enzymol. 516:279–97 [Google Scholar]
  91. Mugford ST, Osbourn A. 91.  2010. Evolution of serine carboxypeptidase-like acyl transferases in the monocots. Plant Signal. Behav. 5:193–95 [Google Scholar]
  92. Mugford ST, Qi X, Bakht S, Hill L, Wegel E. 92.  et al. 2009. A serine carboxypeptidase-like acyltransferase is required for synthesis of antimicrobial compounds and disease resistance in oats. Plant Cell 21:2473–84 [Google Scholar]
  93. Mylona P, Owatworakit A, Papadopoulou K, Jenner H, Qin B. 93.  et al. 2008. Sad3 and Sad4 are required for saponin biosynthesis and root development in oat. Plant Cell 20:201–12 [Google Scholar]
  94. Naoumkina MA, Modolo LV, Huhman DV, Urbanczyk-Wochniak E, Tang Y. 94.  et al. 2010. Genomic and coexpression analyses predict multiple genes involved in triterpene saponin biosynthesis in Medicago truncatula. Plant Cell 22:850–66 [Google Scholar]
  95. Nelson D, Werck-Reichhart D. 95.  2011. A P450-centric view of plant evolution. Plant J. 66:194–211 [Google Scholar]
  96. Ng TB, Liu F, Lu Y, Cheng CHK, Wang Z. 96.  2003. Antioxidant activity of compounds from the medicinal herb Aster tataricus. Comp. Biochem. Physiol. C 136:109–15 [Google Scholar]
  97. Ohyama K, Suzuki M, Kikuchi J, Saito K, Maranaka T. 97.  2009. Dual biosynthetic pathways to phytosterol via cyclartenol and lanosterol in Arabidopsis. Proc. Natl. Acad. Sci. USA 106:725–30 [Google Scholar]
  98. Oldfield E, Lin FY. 98.  2012. Terpene biosynthesis: modularity rules. Angew. Chem. 51:1124–37 [Google Scholar]
  99. Osbourn A, Goss RJM, Field RA. 99.  2011. The saponins—polar isoprenoids with important and diverse biological activities. Nat. Prod. Rep. 28:1261–68 [Google Scholar]
  100. Osbourn A, Papadopoulou KK, Qi X, Field B, Wegel E. 100.  2012. Finding and analyzing plant metabolic gene clusters. Methods Enzymol. 517:113–38 [Google Scholar]
  101. Ourisson G, Albrecht P. 101.  1992. Hopanoids. 1. Geohopanoids—the most abundant natural products on Earth. Acc. Chem. Res. 25:398–402 [Google Scholar]
  102. Owatworakit A, Townsend B, Louveau T, Jenner J, Rejzek M. 102.  et al. 2013. Glycosyltransferases from oat (Avena) implicated in the acylation of avenacins. J. Biol. Chem. 288:3696–704 [Google Scholar]
  103. Papadopoulou K, Melton RE, Leggett M, Daniels MJ, Osbourn AE. 103.  1999. Compromised disease resistance in saponin-deficient plants. Proc. Natl. Acad. Sci. USA 96:12923–28 [Google Scholar]
  104. Phillips DR, Rasbery JM, Bartel B, Matsuda SPT. 104.  2006. Biosynthetic diversity in plant triterpene cyclization. Curr. Opin. Plant Biol. 9:305–14 [Google Scholar]
  105. Podolak I, Galanty A, Sobolewska D. 105.  2010. Saponins as cytotoxic agents: a review. Phytochem. Rev. 9:425–74 [Google Scholar]
  106. Poppenberger B, Fujioka S, Soeno K, George GL, Vaistij FE. 106.  et al. 2005. The UGT73C5 of Arabidopsis thaliana glucosylates brassinosteroids. Proc. Natl. Acad. Sci. USA 102:15253–58 [Google Scholar]
  107. Qi X, Bakht S, Leggett M, Maxwell C, Melton R, Osbourn A. 107.  2004. A gene cluster for secondary metabolism in oat: implications for the evolution of metabolic diversity in plants. Proc. Natl. Acad. Sci. USA 101:8233–38 [Google Scholar]
  108. Qi X, Bakht S, Qin B, Leggett M, Hemmings A. 108.  et al. 2006. A different function for a member of an ancient and highly conserved cytochrome P450 family: from essential sterols to plant defense. Proc. Natl. Acad. Sci. USA 103:18848–53 [Google Scholar]
  109. Racolta S, Juhl PB, Sirim D, Pleiss J. 109.  2012. The triterpene cyclase protein family: a systematic analysis. Proteins 80:2009–19 [Google Scholar]
  110. Reinert DJ, Balliano G, Schulz GE. 110.  2004. Conversion of squalene to the pentacarbocyclic hopene. Chem. Biol. 11:121–26 [Google Scholar]
  111. Rétey R. 111.  1990. Enzymic reaction selectivity by negative catalysis or how do enzymes deal with highly reactive intermediates?. Angew. Chem. Int. Ed. 29:355–61 [Google Scholar]
  112. Saimaru H, Orihara Y, Tansakul P, Kang YH, Shibuya M, Ebizuka Y. 112.  2007. Production of triterpene acids by cell suspension cultures of Olea europaea. Chem. Pharm. Bull. 55:784–88 [Google Scholar]
  113. Sainsbury F, Lomonossoff GP. 113.  2008. Extremely high-level and rapid transient protein production in plants without the use of viral replication. Plant Physiol. 1481212–18
  114. Sainsbury F, Sack M, Stadlmann J, Quendler H, Fischer R. 114.  et al. 2010. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody. PLoS ONE 5:e13976 [Google Scholar]
  115. Sainsbury F, Saxena P, Geisler K, Osbourn A, Lomonossoff G. 115.  2012. Using a virus-derived system to manipulate plant natural product biosynthetic pathways. Methods Enzymol. 517:185–202 [Google Scholar]
  116. Sainsbury F, Thuenemann EC, Lomonossoff GP. 116.  2009. pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol. J. 7:682–93 [Google Scholar]
  117. Sato T, Hoshino T. 117.  2001. Catalytic function of the residues of phenylalanine and tyrosine conserved in squalene-hopene cyclases. Biosci. Biotechnol. Biochem. 65:2233–42 [Google Scholar]
  118. Sawai S, Akashi T, Sakurai N, Suzuki H, Shibata D. 118.  et al. 2006. Plant lanosterol synthase: divergence of the sterol and triterpene biosynthetic pathways in eukaryotes. Plant Cell Physiol. 47:673–77 [Google Scholar]
  119. Sawai S, Saito K. 119.  2011. Triterpenoid biosynthesis and engineering in plants. Front. Plant Sci. 2:25 [Google Scholar]
  120. Sawai S, Shindo T, Sato S, Kaneko T, Tabata S. 120.  et al. 2006. Functional and structural analysis of genes encoding oxidosqualene cyclases of Lotus japonicus. Plant Sci. 170:247–57 [Google Scholar]
  121. Sawai S, Uchiyama H, Mizuno S, Aoki T, Akashi T. 121.  et al. 2011. Molecular characterization of an oxidosqualene cyclase that yields shionone, a unique tetracyclic triterpene ketone of Aster tataricus. FEBS Lett. 585:1031–36 [Google Scholar]
  122. Saxena P, Hsieh YC, Alvarado VY, Sainsbury F, Saunders K. 122.  et al. 2011. Improved foreign gene expression in plants using a virus-encoded suppressor of RNA silencing modified to be developmentally harmless. Plant Biotechnol. J. 9:703–12 [Google Scholar]
  123. Sayama T, Ono E, Takagi K, Takada Y, Horikawa M. 123.  et al. 2012. The Sg-1 glycosyltransferase locus regulates structural diversity of triterpenoid saponins of soybean. Plant Cell 24:2123–38 [Google Scholar]
  124. Scholz M, Lipinski M, Leupold M, Luftmann H, Harig L. 124.  et al. 2009. Methyl jasmonate induced accumulation of kalopanaxsaponin I in Nigella sativa. Phytochemistry 70:517–22 [Google Scholar]
  125. Segura MJR, Jackson BE, Matsuda SPT. 125.  2003. Mutagenesis approaches to deduce structure-function relationships in terpene synthases. Nat. Prod. Rep. 20:304–17 [Google Scholar]
  126. Segura MJR, Meyer MM, Matsuda SPT. 126.  2000. Arabidopsis thaliana LUP1 converts oxidosqualene to multiple triterpene alcohols and a triterpene diol. Org. Lett. 2:2257–59 [Google Scholar]
  127. Seki H, Ohyama K, Sawai S, Mizutani M, Ohnishi T. 127.  et al. 2008. Licorice β-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc. Natl. Acad. Sci. USA 105:14204–9 [Google Scholar]
  128. Seki H, Sawai S, Ohyama K, Mizutani M, Ohnishi T. 128.  et al. 2011. Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin. Plant Cell 23:4112–23 [Google Scholar]
  129. Shan H, Segura MJR, Wilson WK, Lodeiro S, Matsuda SPT. 129.  2005. Enzymatic cyclization of dioxidosqualene to heterocyclic triterpenes. J. Am. Chem. Soc. 127:18008–9 [Google Scholar]
  130. Shibuya M, Adachi S, Ebizuka Y. 130.  2004. Cucurbitadienol synthase, the first committed enzyme for cucurbitacin biosynthesis, is a distinct enzyme from cycloartenol synthase for phytosterol biosynthesis. Tetrahedron 60:6995–7003 [Google Scholar]
  131. Shibuya M, Hoshino M, Katsube Y, Hayashi H, Kushiro T, Ebizuka Y. 131.  2006. Identification of β-amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay. FEBS J. 273:948–59 [Google Scholar]
  132. Shibuya M, Katsube Y, Otsuka M, Zhang H, Tansakul P. 132.  et al. 2009. Identification of a product specific β-amyrin synthase from Arabidopsis thaliana. Plant Physiol. Biochem. 47:26–30 [Google Scholar]
  133. Shibuya M, Nishimura K, Yasuyama N, Ebizuka Y. 133.  2010. Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max. FEBS Lett. 584:2258–64 [Google Scholar]
  134. Shibuya M, Sagara A, Saitoh A, Kushiro T, Ebizuka Y. 134.  2008. Biosynthesis of baccharis oxide, a triterpene with a 3,10-oxide bridge in the A-ring. Org. Lett. 10:5071–74 [Google Scholar]
  135. Shibuya M, Xiang T, Katsube Y, Otsuka M, Zhang H, Ebizuka Y. 135.  2007. Origin of structural diversity in natural triterpenes: direct synthesis of seco-triterpene skeletons by oxidosqualene cyclase. J. Am. Chem. Soc. 129:1450–55 [Google Scholar]
  136. Shibuya M, Zhang H, Endo A, Shishikura K, Kushiro T, Ebizuka Y. 136.  1999. Two branches of the lupeol synthase gene in the molecular evolution of plant oxidosqualene cyclases. Eur. J. Biochem. 266:302–7 [Google Scholar]
  137. Shinozaki J, Shibuya M, Masuda K, Ebizuka Y. 137.  2008. Squalene cyclase and oxidosqualene cyclase from a fern. FEBS Lett. 582:310–18 [Google Scholar]
  138. Shirley AM, Chapple C. 138.  2003. Biochemical characterisation of sinapoyl:choline sinapoyltransferase, a serine carboxypeptidase-like protein that functions as an acyltransferase in plant secondary metabolism. J. Biol. Chem. 278:19870–77 [Google Scholar]
  139. Stapleton A, Allen PV, Friedman M, Belknap WR. 139.  1991. Purification and characterization of solanidine glucosyltransferase from the potato (Solanum tuberosum). J. Agric. Food Chem. 39:1187–93 [Google Scholar]
  140. Suzuki H, Achnine L, Xu R, Matsuda SPT, Dixon RA. 140.  2002. A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula. Plant J. 32:1033–48 [Google Scholar]
  141. Suzuki M, Xiang T, Ohyama K, Seki H, Saito K. 141.  et al. 2006. Lanosterol synthase in dicotyledonous plants. Plant Cell Physiol. 47:565–71 [Google Scholar]
  142. Szakiel A, Paczkowski C, Pensec F, Bertsch C. 142.  2012. Fruit cuticular waxes as a source of biologically active triterpenoids. Phytochem. Rev. 11:263–84 [Google Scholar]
  143. Tamura K, Peterson D, Peterson N, Stecher G, Nei M. 143.  et al. 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28:2731–39 [Google Scholar]
  144. Tansakul P, Shibuya M, Kushiro T, Ebizuka Y. 144.  2006. Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Lett. 580:5143–49 [Google Scholar]
  145. Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J. 145.  et al. 2004. Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature 432:118–22 [Google Scholar]
  146. van Dyck S, Gerbaux P, Flammang P. 146.  2010. Qualitative and quantitative saponin contents in five sea cucumbers from the Indian Ocean. Mar. Drugs 8:173–89 [Google Scholar]
  147. Vincken J-P, Heng L, de Groot A, Gruppen H. 147.  2007. Saponins, classification and occurrence in the plant kingdom. Phytochemistry 68:275–97 [Google Scholar]
  148. Vogt T, Jones P. 148.  2000. Glycosyltransferases in plant natural product synthesis: characterization of a supergene family. Trends Plant Sci. 5:380–86 [Google Scholar]
  149. Wang Z, Guhling O, Yao R, Li F, Yeats TH. 149.  et al. 2011. Two oxidosqualene cyclases responsible for biosynthesis of tomato fruit cuticular triterpenoids. Plant Physiol. 155:540–52 [Google Scholar]
  150. Wang Z, Yeats T, Han H, Jetter R. 150.  2010. Cloning and characterization of oxidosqualene cyclases from Kalanchoe daigremontiana: enzymes catalyzing up to 10 rearrangement steps yielding friedelin and other triterpenoids. J. Biol. Chem. 285:29703–12 [Google Scholar]
  151. Warnecke DC, Baltrusch M, Buck F, Wolter FP, Heinz E. 151.  1997. UDP-glucose:sterol glucosyltransferase: cloning and functional expression in Escherichia coli. Plant Mol. Biol. 35:597–603 [Google Scholar]
  152. Warnecke DC, Heinz E. 152.  1994. Purification of a membrane-bound UDP-glucose: sterol β-d-glucosyltransferase based on its solubility in diethyl ether.. Plant Physiol. 105:1067–73 [Google Scholar]
  153. Wendt KU. 153.  2005. Enzyme mechanisms for triterpene cyclization: new pieces of the puzzle. Angew. Chem. Int. Ed. 44:3966–71 [Google Scholar]
  154. Wendt KU, Lenhart A, Schulz GE. 154.  1999. The structure of the membrane protein squalene-hopene cyclase at 2.0 Å resolution. J. Mol. Biol. 286:175–87 [Google Scholar]
  155. Wendt KU, Poralla K, Schulz GE. 155.  1997. Structure and function of a squalene cyclase. Science 277:1811–15 [Google Scholar]
  156. Wendt KU, Schulz GE, Corey EJ, Liu DR. 156.  2000. Enzyme mechanisms for polycyclic triterpene formation. Angew. Chem. Int. Ed. 39:2812–33 [Google Scholar]
  157. Winzer T, Gazda V, He Z, Kaminski F, Kern M. 157.  et al. 2012. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science 336:1704–8 [Google Scholar]
  158. Wu T-K, Chang C-H, Liu Y-T, Wang T-T. 158.  2008. Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase: a chemistry–biology interdisciplinary study of the protein's structure–function–reaction mechanism relationships. Chem. Rec. 8:302–25 [Google Scholar]
  159. Wu T-K, Liu Y-T, Chang C-H, Yu M-T, Wang H-J. 159.  2006. Site-saturated mutagenesis of histidine 234 of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase demonstrates dual functions in cyclization and rearrangement reactions. J. Am. Chem. Soc. 128:6414–19 [Google Scholar]
  160. Wu T-K, Yu M-T, Liu Y-T, Chang C-H, Wang H-J, Diau EW-G. 160.  2006. Tryptophan 232 within oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae influences rearrangement and deprotonation but not cyclization reactions. Org. Lett. 8:1319–22 [Google Scholar]
  161. Xiang T, Shibuya M, Katsube Y, Tsutsumi T, Otsuka M. 161.  et al. 2006. A new triterpene synthase from Arabidopsis thaliana produces a tricyclic triterpene with two hydroxyl groups. Org. Lett. 8:2835–38 [Google Scholar]
  162. Xiong Q, Wilson WK, Matsuda SPT. 162.  2006. An Arabidopsis oxidosqualene cyclase catalyzes iridal skeleton formation by Grob fragmentation. Angew. Chem. Int. Ed. 45:1285–88 [Google Scholar]
  163. Xu R, Fazio GC, Matsuda SPT. 163.  2004. On the origins of triterpenoid skeletal diversity. Phytochemistry 65:261–91 [Google Scholar]
  164. Xue Z, Duan L, Liu D, Guo J, Ge S. 164.  et al. 2012. Divergent evolution of oxidosqualene cyclases in plants. New Phytol. 193:1022–38 [Google Scholar]
  165. Yonekura-Sakakibara K, Hanada K. 165.  2011. An evolutionary view of functional diversity in family 1 glycosyltransferases. Plant J. 66:182–93 [Google Scholar]
  166. Yu F, Thamm AMK, Reed D, Villa-Ruano N, Quesada AL. 166.  et al. 2013. Functional characterization of amyrin synthase involved in ursolic acid biosynthesis in Catharanthus roseus leaf epidermis. Phytochemistry 91:122–27 [Google Scholar]
  167. Zhang H, Shibuya M, Yokota S, Ebizuka Y. 167.  2003. Oxidosqualene cyclases from cell suspension cultures of Betula platyphylla var. japonica: molecular evolution of oxidosqualene cyclases in higher plants. Biol. Pharm. Bull. 26:642–50 [Google Scholar]

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