OJMC  Vol.2 No.2 , June 2012
Relevant Enzymes, Genes and Regulation Mechanisms in Biosynthesis Pathway of Stilbenes
Abstract: Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the progresses of study on relevant enzymes, genes, and regulation mechanism in biosynthesis pathway of stilbenes are described. Here we introduce a holistic and systematic method of researching relevant enzymes, genes and other regulatory factors in biosynthesis pathway of stilbenes—Systems biology. The application of knowledge of relative enzymes, genes and regulation mechanisms in stilbenes biosynthesis in metabolic engineering which is used as a tool of improving the disease resistance of plants and health caring quality of crops is also discussed.
Cite this paper: D. LU, W. ZHAO and S. ZHAO, "Relevant Enzymes, Genes and Regulation Mechanisms in Biosynthesis Pathway of Stilbenes," Open Journal of Medicinal Chemistry, Vol. 2 No. 2, 2012, pp. 15-23. doi: 10.4236/ojmc.2012.22003.

[1]   B. Delaunois, S. Cordelier and A. Conreux1, “Molecular Engineering of Resveratrol in Plants,” Plant Biotechno- logy Journal, Vol. 7, No. 1, 2009, pp. 2-12. doi:10.1111/j.1467-7652.2008.00377.x

[2]   J. K. Lin and S. H. Tsai, “Chemoprevention of Cancer and Cardiovascular Disease by Resveratrol,” Proceedings of the National Science Council, Republic of China (Part B), Vol. 23, No.3, 1999, pp. 99-106.

[3]   K. Likhitwitayawuid and B. Sritularak, “A New Dimeric Stilbene with Tyrosinase Inhibitory Activity from Artocarpus Gomezianus,” Journal of Natural Products, Vol. 64, 2001, pp. 1457-1459. doi:10.1021/np0101806

[4]   S. L. He, J. C. Zheng and M. Lin, “Advances of Biological Function, Regulatory Mechanism of Biosynthesis and Ge- netic Engineering of in Stilbenes Plant,” Journal of Agricultural Biotechnology, Vol. 12, No. 1, 2004, pp. 102- 108.

[5]   H. C. Zhang, J. M. Liu and H. M. Chen, “Up-Regulation of Licochalcone A Biosynthesis and Secretiony Tween 80 in Hairy Root Cultures of Glycyrrhiza Uralensis Fisch,” Molecular Biotechnology, Vol. 47, No. 1, 2011, pp. 50- 56. doi:10.1007/s12033-010-9311-4

[6]   L. Li, Y. Zhao and J. L. Ma, “Recent Progress on Key Enzymes: PAL, C4H, 4CL of Phenylalanine Metabolism Pathway,” China Journal of Bioinformatics, Vol. 4, 2007, pp. 187-189.

[7]   S. Rasmussen and R. A. Dixon, “Transgene-Mediated and Elicitor-Induced Perturbation of Metabolic Channeling at the Entry Point into the Phenylpropanoid Pathway,” Plant Cell, Vol. 11, 1999, pp. 1537-1551. doi:10.2307/3870981

[8]   T. Fahrendorf and R. A. Dixon, “Stress Responses in Al- falfa (Medicago Sativa L). XVШ: Molecular Cloning and Expression of the Elicitor-Inducible Cinnamic Acid 4- Hydroxylase Cytochrome P450,” Archives of Biochemistry and Biophysics, Vol. 305, No. 2, 1993, p. 509. doi:10.1006/abbi.1993.1454

[9]   H. G. Teutsch, M. P. Hasenfratz and A. Lesot, “Isolation and Sequence of a cDNA Encoding the Jerusalem Artichoke Cinnamate 4-Hydroxylase, a Major Plant Cytochrome P450 Involved in the General Phenylpropanoid Pathway,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 9, 1993, p. 4102. doi:10.1073/pnas.90.9.4102

[10]   C. R. Buell and S. C. Somerville, “Expression of Defense-Related and Putative Signaling Genes during Tolerant and Susceptible Interactions of Arabidopsis with Xanthomonas Campestris PV. Campestris,” Molecular Plant-Microbe Interactions, Vol. 8, No. 3, 1995, pp. 435- 443. doi:10.1094/MPMI-8-0435

[11]   Y. Batard, M. Schalk and M. A. Pierrel, “Regulation of the Cinnamate 4-Hydroxylase (CYP73A1) in Jerusalem Arti- choke Tubers in Response to Wounding and Chemical Treatments,” Plant Physiology, Vol. 113, No. 3, 1997, pp. 951-959.

[12]   D. A. Bell-Lelong, J. C. Cusumano and K. Meyer, “Cinnamate 4-Hydroxylase Expression in Arabidopsis,” Plant Physiology, Vol. 113, No.3, 1997, pp. 729-738. doi:10.1104/pp.113.3.729

[13]   M. Mizutani, D. Ohta and R. Sato, “Isolation of cDNA and a Genomic Clone Encoding Cinnamate 4-Hydroxylase from Arabidopsis and Its Expression Manner in Planta,” Plant Physiology, Vol. 113, No. 3, 1997, pp. 755-763. doi:10.1104/pp.113.3.755

[14]   B. S. Winkel, “Metabolic Channeling in Plant,” Annual Review of Plant Biology, Vol. 55, 2004, pp. 85-107. doi:10.1146/annurev.arplant.55.031903.141714

[15]   X. Y. Dong, E. L. Braun and E. Grotewold, “Functional Conservation of Plant Secondary Metabolic Enzymes Revealed by Comp Lamentation of a Rabidopsis Fla- vonoid Mutants with Maize Genes,” Plant Physiology, Vol. 127, 2001, pp. 46-57. doi:10.1104/pp.127.1.46

[16]   I. E. Burbulis and B. Winkel-Shirley, “Interactions among Enzymes of the Arabidopsis Flavonoid Biosynthestic Pathway,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 22, 1999, pp. 12929-12934. doi:10.1073/pnas.96.22.12929

[17]   X. Z. He, and R. A. Dixon, “Genetic Manipulation of Isoflvone 7-O-Methyltransferase Enhances Biosynthesis of 4’-O-Methylated Isoflavonoid Phytoalexins and Di- sease Resistance in Alfalfa,” Plant Cell, Vol. 12, 2001, pp. 1689-1702. doi:10.2307/3871183

[18]   C. Chapple, “Molecular-Genetic Analysis of Plant Cytochrome P450-Dependent Monooxygenases,” Annual Review of Plant Biology, Vol. 49, 1998, pp. 311-343. doi:10.1146/annurev.arplant.49.1.311

[19]   B. Winkel-Shirley, “Flavonoids Biosynthesis: A Colorful Model for Genetics, Biochemistry, Cell Biology, and Bio- technology,” Plant Physiology, Vol. 126, 2001, pp. 485- 493. doi:10.1104/pp.126.2.485

[20]   R. A. Dixon, “Natural Products and Plant Disease Resistance,” Nature, Vol. 411, No. 14, 2001, pp. 843-847. doi:10.1038/35081178

[21]   M. B. Austin and J. P. Noel, “The Chalcone Synthase Su-Perfamily of Type Ш Polyketide Synthases,” Natural Product Reports, Vol. 20, No. 1, 2003, pp. 79-110. doi:10.1039/b100917f

[22]   K. Hanhineva, H. Kokko and H. Siljanen, “Stilbene Synthase Gene Transfer Caused Alterations in the Phenylpropanoid Metabolism of Transgenic Strawberry,” Jour- nal of Experimental Botany, Vol. 60, No. 7, 2009, pp. 2093-2106. doi:10.1093/jxb/erp085

[23]   H. Morita, H. Noguchi and J. Schroder, “Novel Polyketides Synthesized with a Higher Plant Stilbene Synthase,” European Journal of Biochemistry, Vol. 268, No. 13, 2001, pp. 3759-3766. doi:10.1046/j.1432-1327.2001.02289.x

[24]   S. Rasmussen and R. A. Dixon, “Transgene-Mediated and Elicitor-Induced Perturbation of Metabolic Channeling at the Entry Point into the Phenylpropanoid Pathway,” Plant Cell, Vol. 11, 1999, pp. 1537-1551. doi:10.2307/3870981

[25]   H. E. Shuilin, J. G. Zheng, X. F. Wang, “Plant Secondary Metabolism: Function, Regulation and Gene Engineering,” Chinese Journal of Applied & Environmental Bi- ology, Vol. 8, No. 5, 2002, pp. 558-563.

[26]   F. Melchior and H. Kindl, “Coordinate- and Elicitor- Dependent Expression of Stilbene Synthase and Phenyl- alanine Ammonialyase Genes in Vitis cv. Optima,” Ar- chives of Biochemistry and Biophysics, Vol. 288, No. 2, 1991, pp. 552-557. doi:10.1016/0003-9861(91)90234-A

[27]   D. J. Kliebenstein, “Secondary Metabolites and Plant/ Environment Interactions: A View through Arabidopsis Thaliana Tinged Glasses,” Plant Cell and Environment, Vol. 27, No. 6, 2004, pp. 675-684. doi:10.1111/j.1365-3040.2004.01180.x

[28]   M. Lerdau, “Benefits of the Carbon-Nutrient Balance Hypothesis,” Oikos, Vol. 98, No. 3, 2011, pp. 534-536. doi:10.1034/j.1600-0706.2002.980318.x

[29]   M. A. Lila, “The Nature-Versus-Nurture Debate on Bioactive Phytochemicals: The Genome Versus Terroir,” Jour- nal of the Science of Food and Agriculture, Vol. 86, No. 15, 2006, pp. 2510-2515. doi:10.1002/jsfa.2677

[30]   Z. L. Yuan, C. C. Dai and L. Q. Chen, “Regulation and Accumulation of Secondary Metabolites in Plant-Fungus Symbiotic System,” African Journal of Biotechnology, Vol. 6, No. 11, 2007, pp. 1266-1271.

[31]   D. V. Endt, J. W. Kijne and J. Memelink, “Transcription Factors Controlling Plant Secondary Metabolism: What Regulates the Regulators?” Phytochemistry, Vol. 61, No. 2, 2002, pp. 107-114. doi:10.1016/S0031-9422(02)00185-1

[32]   I. M. Chung, M. R. Park and S. Rehman, “Tissue Specific and Inducible Expression of Resveratrol Synthase Gene in Peanut Plants,” Molecules and Cells, Vol. 12, No. 3, 2001, pp. 353-359.

[33]   H. Chiron, A. Drouet and A. C. Claudot, “Molecular Cloning and Functional Expression of a Stress-Induced Multifunctional O-Methyltransferase with Pinosylvin Me- thyltransferase Activity from Scots Pine (Pines sylvestris L.),” Plant Molecular Biology, Vol. 44, No. 6, 2000, pp. 733-745. doi:10.1023/A:1026507707186

[34]   E. Cantos, J. C. Espin and F. A. Tomas-Barberan, “Postharvest Induction Modeling Method Using UV Irradiation Pulses for Obtaining Resveratrol-Enriched Table Grapes: A New Functional Fruit?” Journal of Agricultural and Food Chemistry, Vol. 49, No. 10, 2001, pp. 5052-5058. doi:10.1021/jf010366a

[35]   H. Kitano, “Systems Biology: Toward System-Level Understanding of Biological Systems,” MIT Press, Cambridge, 2002.

[36]   M. Latterich, “Molecular Systems Biology at the Crossroads: To Know Less about More, or to Know More about Less?” Proteome Science, Vol. 3, 2005, pp. 8-11. doi:10.1186/1477-5956-3-8

[37]   L. Hood, J. R. Heath and M. E. Phelps, “Systems Biology and New Technologies Enable Predictive and Preventative Medicine,” Science, Vol. 305, No. 5696, 2004, pp. 640-643. doi:10.1126/science.1104635

[38]   K.-M. Oksman-Caldentey, D. Inze and M. Oresic, “Connecting Genes Tometabolites by a Systems Biology Approach,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 27, 2004, pp. 9949-9950. doi:10.1073/pnas.0403636101

[39]   A. Aderem, “Systems Biology: Its Practice and Challenges,” Cell, Vol. 121, No. 4, 2005, pp. 511-513. doi:10.1016/j.cell.2005.04.020

[40]   J. X. Wang, Y. Sun and P. L. Xu, “Research Progress in Functional Plant Genomics,” Biotechnology Bulletin, Vol. 1, 2004, pp. 18-24.

[41]   W. A. Rensink and C. R. Buell, “Microarray Expression Profiling Resources for Plant Genomics,” Trends in Plant Science, Vol. 10, No. 12, 2005, pp. 603-612. doi:10.1016/j.tplants.2005.10.003

[42]   V. Marnik, D. P. Johan and M. J. T. van Eijk, “AFLP- Based Transcript Profiling (cDNA-AFLP) for Genome- Wide Expression Analysis,” Nature Protocols, Vol. 2, No. 6, 2007, pp. 1399-1413. doi:10.1038/nprot.2007.174

[43]   W. Jia, P. Liu and J. Jiang, “Application of Metabonomics in Complicated Theory System Research of Traditional Chinese Medicine,” China Journal of Chinese Materia Medica, Vol. 31, No. 8, 2006, pp. 621-625.

[44]   L. W. Qi, P. Li and J. Zhao, “Metabonomics and Mo- dernization of TMC Research,” World Science and Technology, Vol. 8, No. 6, 2006, pp. 79-87.

[45]   L. W. Sumner, P. Mendes and R. A. Dixon, “Plant Me- tabolomics: Large-Scale Phytochemistry in the Functional Genomics Era,” Phytochemistry, Vol. 62, No. 6, 2003, pp. 817-836. doi:10.1016/S0031-9422(02)00708-2

[46]   L. Q. Huang, W. Gao and J. Zhou, “Systems Biology Applications to Explore Secondary Metabolites in Medicinal Plants,” China Journal of Chinese Materia Medica, Vol. 35, No. 1, 2010, pp. 8-12.

[47]   G. H. Cui, L. Q. Huang and X. J. Tang, “Functional Genomics Studies of Salvia Miltiorrhiza ? Establish cDNA Microarray of S. miltiorrhiza,” China Journal of Chinese Materia Medica, Vol. 32, No. 12, 2007, pp. 1137-1142.

[48]   W. Gao, G. H. Cui and J. Q. Kong, “Optimizing Expression and Purification of Recombinant Salvia Miltiorrhiza Copalyl Diphosphate Synthase Protein in E. coli and Preparation of Rabbit Antiserum Against SmCPS,” Acta Pharmaceutica Sinica, Vol. 43, No. 7, 2008, pp. 766.

[49]   X. Y. Wang, G. H. Cui and L. Q. Huang, “A Full Length cDNA of 4-(Cytidine 5’-Diphospho)-2-C-Methyl-D-Ery- thritol Kinase Cloning and Analysis of Introduced Gene Expressing in Sava Miltiorrhiza,” Acta Pharmaceutica Sinica, Vol. 43, No. 12, 2008, pp. 1251-1259.

[50]   W. Gao, M. L. Hillwig and L. Q. Huang, “A Functional Genomics Approach to Tanshinone Biosynthesis Provides Stereo-Chemical Insights,” Organic Letters, Vol. 11, No. 22, 2009, pp. 5170-5173. doi:10.1021/ol902051v

[51]   S. J. Sheng, Z. Y. Liu and W. Zhao, “Molecular Analysis of a Type Ш Polyketide Synthase Gene in Fallopia Multi?ora,” Section Cellular and Molecular Biology, Vol. 65, No. 6, 2010, pp. 939-946.

[52]   Z. Y. Liu, C. X. Zhuang and S. J. Sheng, “Overexpression of a Resveratrol Synthase Gene (PcRS) from Polygonum Cuspidatum in Transgenic Arabidopsis Causes the Accumulation of Trans-Piceid with Antifungal Activity,” Plant Cell Reports, Vol. 30, No. 11, 2011, pp. 2027-2036. doi:10.1007/s00299-011-1110-2

[53]   S. Raiber, G. Schroder and J. Schroder, “Molecular and Enzymatic Characterization of Two Stilbene Synthases from Eastern White Pine (Pinus strobus). A Single Arg/ His Difference Determines the Activity and the pH Dependence of the Enzymes,” FEBS Letters, Vol. 361, No. 2-3, 1995, pp. 229-302. doi:10.1016/0014-5793(95)00199-J

[54]   R. Hain, B. Bleseler, H. Kindl, G. Schroder, R. Stocker, “Expression of a Stilbene Synthase Gene in Nicotiana Tabacumresults in Synthesis of the Phytoalexin Resveratrol,” Plant Molecular Biology, Vol. 15, No. 2, 1990, pp. 325-335. doi:10.1007/BF00036918

[55]   R. Hain, H. J. Reif and E. Krause, “Disease Resistance Results from Foreign Phytoalexin Expression in a Novel Plant,” Nature, Vol. 361, No. 6408, 1993, pp. 153-156. doi:10.1038/361153a0

[56]   W. Z. Tian, L. Ding and S. Y. Cao, “Rice Transformation with a Phytoalexin Gene and Bioassay of the Transgenic Plants,” Acta Botanica Sinica, Vol. 40, No. 9, 1998, pp. 803-808.

[57]   L. Serazetdinova, K. H. Oldach and H. L?rz, “Expression of Transgenic Stilbene Synthases in Wheat Causes the Accumulation of Unknown Stilbene Derivatives with Antifungal Activity,” Plant Physiology, Vol. 162, No. 9, 2005, pp. 985-1002. doi:10.1016/j.jplph.2004.11.005

[58]   I. Szankowski, K. Briviba and J. Fleschhut, “Transformation of Apple (Malus domestica Borkh.) with the Stilbene Synthase Gene from Grapevine (Vitis vinifera L.) and a PGIP Gene from Kiwi (Actinidia deliciosa),” Plant Cell Reports, Vol. 22, No. 2, 2003, pp. 141-150. doi:10.1007/s00299-003-0668-8

[59]   S. K. Sepp?nen, L. Syrj?l?L, et al., “Antifungal Activity of Stilbenes in In Vitro Bioassays and in Transgenic Populus Expressing a Gene Encoding Pinosylvin Synthase,” Plant Cell Reports, Vol. 22, No. 8, 2004, pp. 584 -593.

[60]   Y. J. Zhu, R. Agbayani and M. C. Jackson, “Expression of the Grapevine Stilbene Synthase Gene VST1 in Papaya Provides Increased Resistance Against Diseases Caused by Phytophthora Palmivora,” Planta, Vol. 220, No. 2, 2004, pp. 241-250. doi:10.1007/s00425-004-1343-1

[61]   A. Giorcelli, F. Sparvoli and F. Mattivi, “Expression of the Stilbene Synthase (StSy) Gene from Grapevine in Transgenic White Poplar Results in High Accumulation of the Antioxidant Resveratrol Glucosides,” Transgenic Research, Vol. 13, No. 3, 2004, pp. 203-214. doi:10.1023/B:TRAG.0000034658.64990.7f

[62]   A. Hüsken, A. Baumert and C. Milkowski, “Resveratrol Gluco-Side (Piceid) Synthesis in Seeds of Transgenic Oilseed Rape (Brassica napus L.),” Theoretical and Applied Genetics, Vol. 111, No. 8, 2005, pp. 1553-1562. doi:10.1007/s00122-005-0085-1

[63]   R. Morelli, S. Das and A. Bertelli, “The Introduction of the Stilbene Synthase Gene Enhances the Natural Antiradical Activity of Lycopersicon Esculentum Mill,” Molecular and Cellular Biochemistry, Vol. 82, No. 1-2, 2006, pp. 65-73. doi:10.1007/s11010-006-1260-7

[64]   A. Richter, H. J. Jacobsen and A. de Kathen, “Transgenic Peas (Pisum sativum) Expressing Polygalacturonase Inhibiting Protein from Raspberry (Rubus idaeus) and Stilbene Synthase from Grape (Vitis vinifera),” Plant Cell Reports, Vol. 25, No. 11, 2006, pp. 1166-1173. doi:10.1007/s00299-006-0172-z

[65]   S. Liu, Y. Hu and X. Wang, “High Content of Resveratrol in Lettuce Transformed with a Stilbene Synthase Gene of Parthenocissus Henryana,” Journal of Agricultural and Food Chemistry, Vol. 54, No. 21, 2006, pp. 8082-8825. doi:10.1021/jf061462k

[66]   A. Schwekendiek, O. Spring and A. Heyerick, “Constitutive Expression of a Grapevine Stilbene Synthase Gene in Transgenic Hop (Humulus lupulus L.) Yields Resveratrol and Its Derivatives in Substantial Quantities,” Journal of Agricultural and Food Chemistry, Vol. 55, No. 17, 2007, pp. 7002-7009. doi:10.1021/jf070509e

[67]   C. Lo, J. C. Le Blanc, et al., “Detection, Characterization, and Quantification of Resveratrol Glycosides in Transgenic Arabidopsis over—Expressing a Sorghum Stilbene Synthase Gene by Liquid Chromatography/Tandem Mass Spectrometry,” Rapid Communications in Mass Spectrometry, Vol. 21, No. 24, 2007, pp. 4101-4108. doi:10.1002/rcm.3316