Genomic and coexpression analyses predict multiple genes involved in triterpene saponin biosynthesis in Medicago truncatula

Plant Cell

Volumn 22, Issue 3, 2010, Pages 850-866

  Naoumkina, Marina A ^a   Modolo, Luzia V ^b   Huhman, David V ^a   Urbanczyk Wochniak, Ewa ^a   Tang, Yuhong ^a   Sumner, Lloyd W ^a   Dixon, Richard A ^a  

^a PLANT BIOLOGY DIVISION   (United States)

^b FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ESCHERICHIA COLI; MEDICAGO; MEDICAGO TRUNCATULA;

EID: 77953200019     PISSN: 10404651     EISSN: 1532298X     Source Type: Journal    
DOI: 10.1105/tpc.109.073270     Document Type: Article

References (79)

1. Abe, I., Rohmer, M., and Prestwich, G.D. (1993). Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chem. Rev. 93: 2189-2206.
2. Achnine, L., Huhman, D.V., Farag, M.A., Sumner, L.W., Blount, J.W., and Dixon, R.A. (2005). Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. Plant J. 41: 875-887.
3. Alonso, W.R., and Croteau, R. (1993). Prenyltransferases and cyclases. In Methods in Plant Biochemistry. Enzymes of Secondary Metabolism, P.M. Dey and J.B. Harborne, eds (London: Academic Press), pp. 239-260.
4. Behboudi, S., Morein, B., and Villacres Eriksson, M.C. (1999). Quillaja saponin formulations that stimulate proinflammatory cytokines elicit a potent acquired cell-mediated immunity. Scand. J. Immunol. 50: 371-377.
5. Benedito, V.A., et al. (2008). A gene expression atlas of the model legume Medicago truncatula. Plant J. 55: 504-513.
6. Bowles, D., Isayenkova, J., Lim, E.K., and Poppenberger, B. (2005). Glycosyltransferases: managers of small molecules. Curr. Opin. Plant Biol. 8: 254-263.
7. Bowles, D., Lim, E.K., Poppenberger, B., and Vaistij, F.E. (2006). Glycosyltransferases of lipophilic small molecules. Annu. Rev. Plant Biol. 57: 567-597.
8. Bramley, P.M. (1997). Isoprenoid metabolism. In Plant Biochemistry, P.M. Dey and J.B. Harborne, eds (London: Academic Press), pp. 417-434.
9. Broeckling, C.D., Huhman, D.V., Farag, M., Smith, J.T., May, G.D., Mendes, P., Dixon, R.A., and Sumner, L.W. (2005). Metabolic profiling of Medicago truncatula cell cultures reveals effects of biotic and abiotic elicitors on primary metabolism. J. Exp. Bot. 56: 323-336.
10. Chen, J.C., Chiu, M.H., Nie, R.L., Cordell, G.A., and Qiu, S.X. (2005). Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat. Prod. Rep. 22: 386-399.
11. Chong, J., Baltz, R., Schmitt, C., Beffa, R., Fritig, B., and Saindrenan, P. (2002). Downregulation of a pathogen-responsive tobacco UDPGlc: phenylpropanoid glucosyltransferase reduces scopoletin glucoside accumulation, enhances oxidative stress, and weakens virus resistance. Plant Cell 14: 1093-1107.
12. Dereeper, A., Guignon, V., Blanc, G., Audic, S., Buffet, S., Chevenet, F., Dufayard, J.F., Guindon, S., Lefort, V., Lescot, M., Claverie, J.M., and Gascuel, O. (2008). Phylogeny.fr: Robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 36: W465-469.
13. Dixon, R.A., and Sumner, L.W. (2003). Legume natural products. Understanding and manipulating complex pathways for human and animal health. Plant Physiol. 131: 878-885.
14. Dozmorov, I., and Centola, M. (2003). An associative analysis of gene expression array data. Bioinformatics 19: 204-211.
15. Farag, M.A., Huhman, D.V., Dixon, R.A., and Sumner, L.W. (2008). Metabolomics reveals novel pathways and differential mechanistic and elicitor-specific responses in phenylpropanoid and isoflavonoid biosynthesis in Medicago truncatula cell cultures. Plant Physiol. 146: 387-402.
16. Farag, M.A., Huhman, D.V., Lei, Z., and Sumner, L.W. (2007). Metabolic profiling and systematic identification of flavonoids and isoflavonoids in roots and cell suspension cultures of Medicago truncatula using HPLC-UV-ESI-MS and GC-MS. Phytochemistry 68: 342-354.
17. Field, B., and Osbourn, A.E. (2008). Metabolic diversification Independent assembly of operon-like gene clusters in different plants. Science 320: 543-547.
18. Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grun, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K., and Gierl, A. (1997). Analysis of a chemical plant defense mechanism in grasses. Science 277: 696-699.
19. Gamas, P., Niebel Fde, C., Lescure, N., and Cullimore, J. (1996). Use of a subtractive hybridization approach to identify new Medicago truncatula genes induced during root nodule development. Mol. Plant Microbe Interact. 9: 233-242.
20. Goossens, A., Hakkinen, S.T., Laakso, I., Seppanen-Laakso, T., Biondi, S., De Sutter, V., Lammertyn, F., Nuutila, A.M., Soderlund, H., Zabeau, M., Inze, D., and Oksman-Caldentey, K.M. (2003). A functional genomics approach toward the understanding of secondary metabolism in plant cells. Proc. Natl. Acad. Sci. USA 100: 8595-8600.
21. Grubb, C.D., Zipp, B.J., Ludwig-Muller, J., Masuno, M.N., Molinski, T.F., and Abel, S. (2004). Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis and auxin homeostasis. Plant J. 40: 893-908.
22. Hansen, K.S., Kristensen, C., Tattersall, D.B., Jones, P.R., Olsen, C. E., Bak, S., and Moller, B.L. (2003). The in vitro substrate regiospecificity of recombinant UGT85B1, the cyanohydrin glucosyltransferase from Sorghum bicolor. Phytochemistry 64: 143-151.
23. Haralampidis, K., Trojanowska, M., and Osbourn, A.E. (2002). Biosynthesis of triterpenoid saponins in plants. Adv. Biochem. Eng. Biotechnol. 75: 31-49.
24. Haridas, V., Higuchi, M., Jayatilake, G.S., Bailey, D., Mujoo, K., Blake, M.E., Arntzen, C.J., and Gutterman, J.U. (2001). Avicins: Triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation. Proc. Natl. Acad. Sci. USA 98: 5821-5826.
25. Hayashi, H., Huang, P., Kirakosyan, A., Inoue, K., Hiraoka, N., Ikeshiro, Y., Kushiro, T., Shibuya, M., and Ebizuka, Y. (2001). Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in glycyrrhizin and soyasaponin biosyntheses in licorice. Biol. Pharm. Bull. 24: 912-916.
26. Huhman, D.V., Berhow, M.A., and Sumner, L.W. (2005). Quantification of saponins in aerial and subterranean tissues of Medicago truncatula. J. Agric. Food Chem. 53: 1914-1920.
27. Huhman, D.V., and Sumner, L.W. (2002). Metabolic profiling of saponins in Medicago sativa and Medicago truncatula using HPLC coupled to an electrospray ion-trap mass spectrometer. Phytochemistry 59: 347-360.
28. Irmler, S., Schroder, G., St-Pierre, B., Crouch, N.P., Hotze, M., Schmidt, J., Strack, D., Matern, U., and Schroder, J. (2000). Indole alkaloid biosynthesis in Catharanthus roseus: New enzyme activitiesGenomics of Saponin Biosynthesis 865 and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J. 24: 797-804.
29. Jorgensen, K., Rasmussen, A.V., Morant, M., Nielsen, A.H., Bjarnholt, N., Zagrobelny, M., Bak, S., and Moller, B.L. (2005). Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr. Opin. Plant Biol. 8: 280-291.
30. Kapusta, I., Janda, B., Stochmal, J., and Oleszek, W. (2005a). Determination of saponins in aerial parts of barrel medic (Medicago truncatula) by liquid chromatography-electrospray ionization/mass spectrometry. J. Agric. Food Chem. 53: 7654-7660.
31. Kapusta, I., Stochmal, A., Perrone, A., Piacente, S., Pizza, C., and Oleszek, W. (2005b). Triterpene saponins from barrel medic (Medicago truncatula) aerial parts. J. Agric. Food Chem. 53: 2164-2170.
32. Kendall, W.A., and Leath, K.T. (1976). Effect of saponins on palatability of alfalfa to meadow voles. Agron. J. 68: 473-476.
33. Kevei Z., et al. (2007). 3-Hydroxy-3-methylglutaryl coenzyme a reductase 1 interacts with NORK and is crucial for nodulation in Medicago truncatula. Plant Cell 19: 3974-3989.
34. Lange, B.M., and Ghassemian, M. (2003). Genome organization in Arabidopsis thaliana: A survey for genes involved in isoprenoid and chlorophyll metabolism. Plant Mol. Biol. 51: 925-948.
35. Leek, J.T., Monsen, E., Dabney, A.R., and Storey, J.D. (2006). EDGE: Extraction and analysis of differential gene expression. Bioinformatics 22: 507-508.
36. Li, L., Cheng, H., Gai, J., and Yu, D. (2007). Genome-wide identification and characterization of putative cytochrome P450 genes in the model legume Medicago truncatula. Planta 226: 109-123.
37. Mackenzie, P.I., et al. (1997). The UDP glycosyltransferase gene superfamily: Recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7: 255-269.
38. Meesapyodsuk, D., Balsevich, J., Reed, D.W., and Covello, P.S. (2007). Saponin biosynthesis in Saponaria vaccaria. cDNAs encoding beta-amyrin synthase and a triterpene carboxylic acid glucosyltransferase. Plant Physiol. 143: 959-969.
39. Modolo, L.V., Blount, J.W., Achnine, L., Naoumkina, M.A., Wang, X., and Dixon, R.A. (2007). A functional genomics approach to (iso) flavonoid glycosylation in the model legume Medicago truncatula. Plant Mol. Biol. 64: 499-518.
40. Morita, M., Shibuya, M., Kushiro, T., Masuda, K., and Ebizuka, Y. (2000). Molecular cloning and functional expression of triterpene synthases from pea (Pisum sativum) new alpha-amyrin-producing enzyme is a multifunctional triterpene synthase. Eur. J. Biochem. 267: 3453-3460.
41. Mylona, P., Owatworakit, A., Papadopoulou, K., Jenner, H., Qin, B., Findlay, K., Hill, L., Qi, X., Bakht, S., Melton, R., and Osbourn, A. (2008). Sad3 and sad4 are required for saponin biosynthesis and root development in oat. Plant Cell 20: 201-212.
42. Naoumkina, M., Farag, M.A., Sumner, L.W., Tang, Y., Liu, C.J., and Dixon, R.A. (2007). Different mechanisms for phytoalexin induction by pathogen and wound signals in Medicago truncatula. Proc. Natl. Acad. Sci. USA 104: 17909-17915.
43. Oleszek, W. (1996). Alfalfa Saponins: Structure, Biological Activity, and Chemotaxonomy. (New York: Plenum Press).
44. Oleszek, W., Junkuszew, M., and Stochmal, A. (1999). Determination and toxicity of saponins from Amaranthus cruentus seeds. J. Agric. Food Chem. 47: 3685-3687.
45. Osbourn, A.E. (2003). Saponins in cereals. Phytochemistry 62: 1-4. Osbourn, A.E., and Field, B. (2009). Operons. Cell. Mol. Life Sci. 66: 3755-3775.
46. Peel, G.J., Pang, Y., Modolo, L.V., and Dixon, R.A. (2009). The LAP1 MYB transcription factor orchestrates anthocyanidin biosynthesis and glycosylation in Medicago. Plant J. 59: 136-149.
47. Petit, P.R., Sauvaire, Y.D., Hillaire-Buys, D.M., Leconte, O.M., Baissac, Y.G., Ponsin, G.R., and Ribes, G.R. (1995). Steroid saponins from fenugreek seeds: Extraction, purification, and pharmacological investigation on feeding behavior and plasma cholesterol. Steroids 60: 674-680.
48. Price, K.R., Johnson, I.T., and Fenwick, G.R. (1987). The chemistry and biological significance of saponins in foods and feedstuffs. Crit. Rev. Food Sci. Nutr. 26: 27-135.
49. Qi, X., Bakht, S., Leggett, M., Maxwell, C., Melton, R., and Osbourn, A. (2004). A gene cluster for secondary metabolism in oat: implications for the evolution of metabolic diversity in plants. Proc. Natl. Acad. Sci. USA 101: 8233-8238.
50. Rajput, Z.I., Hu, S.H., Xiao, C.W., and Arijo, A.G. (2007). Adjuvant effects of saponins on animal immune responses. J. Zhejiang Univ. Sci. B 8: 153-161.
51. Ro, D.K., Arimura, G., Lau, S.Y., Piers, E., and Bohlmann, J. (2005). Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase. Proc. Natl. Acad. Sci. USA 102: 8060-8065.
52. Saito, K., Hirai, M.Y., and Yonekura-Sakakibara, K. (2008). Decoding genes with coexpression networks and metabolomics -'Majority report by precogs'. Trends Plant Sci. 13: 36-43.
53. Shao, H., He, X., Achnine, L., Blount, J.W., Dixon, R.A., and Wang, X. (2005). Crystal structures of a multifunctional triterpene/flavonoid glycosyltransferase from Medicago truncatula. Plant Cell 17: 3141-3154.
54. Shibuya, M., Hoshino, M., Katsube, Y., Hayashi, H., Kushiro, T., and Ebizuka, Y. (2006). Identification of beta-amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay. FEBS J. 273: 948-959.
55. Shibuya, M., Katsube, Y., Otsuka, M., Zhang, H., Tansakul, P., Xiang, T., and Ebizuka, Y. (2008). Identification of a product specific betaamyrin synthase from Arabidopsis thaliana. Plant Physiol. Biochem. 47: 26-30.
56. Shimura, K., et al. (2007). Identification of a biosynthetic gene cluster in rice for momilactones. J. Biol. Chem. 282: 34013-34018.
57. Shulaev, V., Cortes, D., Miller, G., and Mittler, R. (2008). Metabolomics for plant stress response. Physiol. Plant. 132: 199-208.
58. Small, E. (1996). Adaptations to herbivory in alfalfa (Medicago sativa). Can. J. Bot. 74: 807-822.
59. Sparg, S.G., Light, M.E., and van Staden, J. (2004). Biological activities and distribution of plant saponins. J. Ethnopharmacol. 94: 219-243.
60. Storey, J.D., and Tibshirani, R. (2003). Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100: 9440-9445.
61. Suzuki, H., Achnine, L., Xu, R., Matsuda, S.P., and Dixon, R.A. (2002). A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula. Plant J. 32: 1033-1048.
62. Suzuki, H., Reddy, M.S.S., Naoumkina, M., Aziz, N., May, G.D., Huhman, D.V., Sumner, L.W., Blount, J.W., Mendes, P., and Dixon, R.A. (2005). Methyl jasmonate and yeast elicitor induce differential genetic and metabolic re-programming in cell suspension cultures of the model legume Medicago truncatula. Planta 220: 698-707.
63. Suzuki, R., and Shimodaira, H. (2006). Pvclust: an R package for assessing the uncertainty in hierarchical clustering. Bioinformatics 22: 1540-1542.
64. Tadege, M., Wen, J., He, J., Tu, H., Kwak, Y., Eschstruth, A., Cayrel, A., Endre, G., Zhao, P.X., Chabaud, M., Ratet, P., and Mysore, K.S. (2008). Large-scale insertional mutagenesis using the Tnt1 retrotransposon in the model legume Medicago truncatula. Plant J. 54: 335-347.
65. Tava, A., and Odoardi, M. (1996). Saponins from Medicago Spp.: Chemical characterization and biological activity against insects. Adv. Exp. Med. Biol. 405: 97-109.
66. Thimm, O., Blasing, O., Gibon, Y., Nagel, A., Meyer, S., Krüger, P., Selbig, J., Muller, L.A., Rhee, S.Y., and Stitt, M. (2004). MAPMAN: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes. Plant J. 37: 914-939.
67. Tusher, V.G., Tibshirani, R., and Chu, G. (2001). Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA 98: 5116-5121.
68. Uematsu, Y., Hirata, K., and Saito, K. (2000). Spectrophotometric determination of saponin in Yucca extract used as food additive. J. AOAC Int. 83: 1451-1454.
69. Urbanczyk-Wochniak, E., and Sumner, L.W. (2007). MedicCyc: A biochemical pathway database for Medicago truncatula. Bioinformatics 23: 1418-1423.
70. Vincken, J.-P., Heng, L., de Groot, A., and Gruppen, H. (2007). Saponins, classification and occurrence in the plant kingdom. Phytochemistry 68: 275-297.
71. von Rad, U., Huttl, R., Lottspeich, F., Gierl, A., and Frey, M. (2001). Two glucosyltransferases are involved in detoxification of benzoxazinoids in maize. Plant J. 28: 633-642.
72. Waller, G.R., and Yamasaki, K. (1996). Saponins Used in Traditional and Modern Medicine. Advances in Experimental Medicine and Biology. (New York: Plenum Press,).
73. Wang, N., Li, Z., Song, D., Li, W., Fu, H., Koike, K., Pei, Y., Jing, Y., and Hua, H. (2008). Lanostane-type triterpenoids from the roots of Kadsura coccinea. J. Nat. Prod. 71: 990-994.
74. Werck-Reichhart, D., Bak, S., and Paquette, S. (2002). Cytochromes P450. In The Arabidopsis Book, C.R. Somerville and E.M. Meyerowitz, eds (Rockville, MD: American Society of Plant Biologists), doi/http://www.aspb.org/publications/arabidopsis
75. Wilderman, P.R., Xu, M., Jin, Y., Coates, R.M., and Peters, R.J. (2004). Identification of syn-pimara-7,15-diene synthase reveals functional clustering of terpene synthases involved in rice phytoalexin/ allelochemical biosynthesis. Plant Physiol. 135: 2098-2105.
76. Woo, H.H., Orbach, M.J., Hirsch, A.M., and Hawes, M.C. (1999). Meristem-localized inducible expression of a UDP-glycosyltransferase gene is essential for growth and development in pea and alfalfa. Plant Cell 11: 2303-2315.
77. Yonekura-Sakakibara, K., Tohge, T., Matsuda, F., Nakabayashi, R., Takayama, H., Niida, R., Watanabe-Takahashi, A., Inoue, E., and Saito, K. (2008). Comprehensive flavonol profiling and transcriptome coexpression analysis leading to decoding gene-metabolite correlations in Arabidopsis. Plant Cell 20: 2160-2176.
78. Yonekura-Sakakibara, K., Tohge, T., Niida, R., and Saito, K. (2007). Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics. J. Biol. Chem. 282: 14932-14941.
79. Zar, J.H. (1999). Biostatistical Analysis. (Upper Saddle River, NJ: Prentice Hall).