Abstract
Catharanthus roseus is an ornamental plant belonging to the Apocynaceae family which produces flowers of different color for most of the year. Besides its importance as an ornamental plant, its interest today is centered on its capacity to biosynthesize a great variety of terpenoid indole alkaloids (TIAs), which have a high added value due to their wide spectrum of pharmaceutical applications. The most important TIAs are the two antitumoral alkaloids, vinblastine and vincristine. Likewise, C. roseus also produces ajmalicine used as antihypertensive and serpentine used as sedative. The high cost of these alkaloids is due to the very small amounts that occur in C. roseus and the difficulty of their extraction which is carried out in the presence of many other compounds. This problem has created the need to find alternative sources to produce these compounds. In this respect, plant tissue/cell cultures could be a useful alternative source of pharmacologically active C. roseus alkaloids, but, even so, these have only been obtained in very low concentrations and after a substantial amount of research. This problem has stimulated intense research into the biosynthesis of TIAs and in the regulation of its pathways, with the aim of increasing the production of these high-value compounds by biotechnological approaches.
The aim of this chapter is centered on different strategies to improve TIA production which have been developed, including screening and selection of high-yield cell lines, optimization of culture conditions, feeding and elicitation strategies, and the metabolic engineering of TIA biosynthetic pathway. An up-to-date view on the biosynthesis of TIAS is also given. Although not yet successful, metabolic engineering offers the most promising perspective for improving TIA production in the future, as increases the knowledge of the genetic determination and regulation of the TIA pathway.
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Abbreviations
- 16OMT:
-
16-hydroxytabersonine 16-O-methyltransferase
- 2,4-D:
-
2,4-dichlorophenoxyacetic acid
- AVLBS:
-
Anhydrovinblastine synthase
- BA:
-
Benzyladenine
- CR:
-
Cathenamine reductase
- CS:
-
Cathenamine synthase
- D4H:
-
Desacetoxyvindoline-4-hydroxylase
- DAT:
-
Deacetylvindoline-4-O-acetyltransferase
- DMAPP:
-
Dimethylallyl diphosphate
- DW:
-
Dry weight
- FW:
-
Fresh weight
- G10H:
-
Geraniol-10-hydroxylase
- GD:
-
Geissoschizine dehydrogenase
- GPP:
-
Geranyl diphosphate
- GPP synthase:
-
Geranyl diphosphate synthase
- IAA:
-
Indole-3-acetic acid
- IPP isomerase:
-
Isopentenyl-diphosphate isomerase
- IPP:
-
Isopentenyl diphosphate
- LAMT:
-
Loganic acid methyltransferase
- MeJa:
-
Methyl jasmonate
- MEP:
-
2-methyl-erythritol 4-phosphate
- NMT:
-
N-methyltransferase
- PNAE:
-
Polyneuridine aldehyde esterase
- Prx:
-
Peroxidases
- SBE:
-
Sarpagan bridge enzyme
- SGD:
-
Strictosidine Ī²-glucosidase
- SLS:
-
Secologanin synthase
- STR:
-
Strictosidine synthase
- T16H:
-
Tabersonine 16-hydroxylase
- TDC:
-
Tryptophan decarboxylase
- TIAs:
-
Terpenoid indole alkaloids
- VH:
-
Vinorine hydroxylase
- VS:
-
Vinorine synthase
References
van der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R (2004) The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 11:1241ā1253.
Loyola-Vargas VM, Galaz-Ćvalos RM, KĆŗ-Cauich R (2007) Catharanthus biosynthetic enzymes: the road ahead. Phytochem Rev 6:307ā339. doi:10.1007/s11101-007-9064-2
Guirimand G, Guihur A, Poutrain P, Hericourt F, Mahroug S, St-Pierre B, Burlat V, Courdavault V (2011) Spatial organization of the vindoline biosynthetic pathway in Catharanthus roseus. J Plant Physiol 168:549ā557. doi:10.1016/j.jplph.2010.08.01
Mahroug S, Burlat V, St-Pierre B (2007) Cellular and sub-cellular organisation of the monoterpenoid indole alkaloid pathway in Catharanthus roseus. Phytochem Rev 6:363ā381. doi:10.1007/s11101-006-9017-1
Memelink J, Gantet P (2007) Transcription factors involved in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Phytochem Rev 6:353ā362. doi:10.1007/s11101-006-9051-z
Shukla AK, Shasany AK, Gupta MM, Khanuja SPS (2006) Transcriptome analysis in Catharanthus roseus leaves and roots for comparative terpenoid indole alkaloid profiles. J Exp Bot 57:3921ā3932. doi:10.1093/jxb/erl146
Rischer H, OreÅ”iÄ M, SeppƤnen-Laakso T, Katajamaa M, Lammertyn F, Ardiles-Diaz W, Van Montagu MCE, InzĆ© D, Oksman-Caldentey KM, Goossens A (2006) Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. Proc Natl Acad Sci USA 103:5614ā5619. doi:10.1073/pnas.0601027103
Contin A, van der Heijden R, Lefeber AW, Verpoorte R (1998) The iridoid glucoside secologanin is derived from the novel triose phosphate/pyruvate pathway in a Catharanthus roseus cell culture. FEBS Lett 434:413ā416. doi:10.1016/S0014-5793(98)01022-9
Ziegler J, Facchini PJ (2008) Alkaloid biosynthesis: metabolism and trafficking. Annu Rev Plant Biol 59:735ā769. doi:10.1146/annurev.arplant.59.032607.092730
Collu G, Unver N, Peltenburg-Looman AMG, van der Heijden R, Verpoorte R, Memelink J (2001) Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett 508:215ā220. doi:10.1016/S0014-5793(01)03045-9
FernĆ”ndez JA, Kurz WGW, De Luca V (1989) Conformation dependent inactivation of tryptophan decarboxylase from Catharanthus roseus. Biochem Cell Biol 67:730ā734. doi:10.1139/o89-109
Islas-Flores IR, Loyola-Vargas VM, Miranda-Ham ML (1994) Tryptophan decarboxylase activity in transformed roots from Catharanthus roseus and its relationship to tryptamine, ajmalicine, and catharanthine accumulation during the culture cycle. In Vitro Cell Dev Biol Plant 30:81ā83. doi:10.1007/BF02632125
Pasquali G, Goddijn OJM, De Waal A, Verpoorte R, Schilperoort RA, Hoge JHC, Memelink J (1992) Coordinated regulation of two indole alkaloid biosynthetic genes from Catharanthus roseus by auxin and elicitors. Plant Mol Biol 18:1121ā1131. doi:10.1007/BF00047715
Goddijn OJM, de Kam RJ, Zanetti A, Schilperoort RA, Hoge JHC (1992) Auxin rapidly down-regulates transcription of the tryptophan decarboxylase gene from Catharanthus roseus. Plant Mol Biol 18:1113ā1120. doi:10.1007/BF00047714
Ouwerkerk PBF, Hallard D, Memelink J (1999) Identification of UV-B light responsive regions in the promoter of the tryptophan decarboxylase gene from Catharanthus roseus. Plant Mol Biol 41:491ā503. doi:10.1023/A:1006321100550
El-Sayed M, Verpoorte R (2007) Catharanthus terpenoid indole alkaloids: biosynthesis and regulation. Phytochem Rev 6:277ā305. doi:10.1007/s11101-006-9047-8
Canel C, Lopes-Cardoso MI, Whitmer S, Van Der Fits L, Pasquali G, van der Heijden R, Hoge JHC, Verpoorte R (1998) Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus. Planta 205:414ā419. doi:10.1007/s004250050338
Ruppert M, Ma XY, Stockigt J (2005) Alkaloid biosynthesis in Rauvolfia ā cDNA cloning of major enzymes of the ajmaline pathway. Curr Org Chem 9:1431ā1444. doi:10.2174/138527205774370540
Pasquali G, Porto DD, Fett-Neto AG (2006) Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids: recent progress related to old dilemma. J Biosci Bioeng 101:287ā296. doi:10.1263/jbb.101.287
Kutchan TM (1993) Strictosidine: from alkaloid to enzyme to gene. Phytochemistry 32:493ā506. doi:10.1016/S0031-9422(00)95128-8
Geerlings A, MartĆnez-Lozano IbaƱez M, Memelink J, van der Heijden R, Verpoorte R (2000) Molecular cloning and analysis of strictosidine Ī²-d-glucosidase, an enzyme in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J Biol Chem 275:3051ā3056. doi:10.1074/jbc.275.5.3051
von Schumann G, Gao S, Stƶckigt J (2002) Vomilenine reductaseāa novel enzyme catalyzing a crucial step in the biosynthesis of the therapeutically applied antiarrhythmic alkaloid ajmaline. Bioorg Med Chem 10:1913ā1918. doi:10.1016/S0968-0896(01)00435-7
Falkenhagen H, Stƶckigt J (1995) Enzymatic biosynthesis of vomilenine, a key intermediate of the ajmaline pathway, catalyzed by a novel cytochrome P450-dependent enzyme from plant cell cultures of Rauwolfia serpentina. Z Naturforsch 50:45ā53. doi:35400005971172.0070
Meijer AH, Verpoorte R, Hoge JHC (1993) Regulation of enzymes and genes involved in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J Plant Res 3:145ā164. doi:35400002408251.0130
Blom TJM, Sierra M, van Vliet TB, Franke-van Dijk MEI, Koning P, van Iren F, Verpoorte R, Libbenga KR (1991) Uptake and accumulation of ajmalicine into isolated vacuoles of cultured cells of Catharanthus roseus (L.) G. Don. and its conversion into serpentine. Planta 183:170ā177. doi:10.1007/BF00197785
Schrƶder G, Unterbusch E, Kaltenbach M, Schmidt J, Strack D, De Luca V, Schrƶder J (1999) Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase. FEBS Lett 458:97ā102. doi:10.1016/S0014-5793(99)01138-2
Levac D, Murata J, Kim WS, De Luca V (2008) Application of carborundum abrasion for investigating the leaf epidermis: molecular cloning of Catharanthus roseus 16-hydroxytabersonine-16-O-methyltransferase. Plant J 53:225ā236. doi:10.1111/j.1365-313X.2007.03337.x
De Luca V, Cutler AJ (1987) Subcellular localization of enzymes involved in indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol 85:1099ā1102.
St-Pierre B, Laflamme P, Alarco AM, De Luca V (1998) The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer. Plant J 14:703ā713. doi:10.1046/j.1365-313x.1998.00174.x
VĆ”zquez-Flota F, De Luca V (1998) Developmental and light regulation of desacetoxyvindoline 4-hydroxylase in Catharanthus roseus. Evidence of a multilevel regulatory mechanism. Plant Physiol 117:1351ā1361. doi:10.1104/pp. 117.4.1351
St-Pierre B, De Luca V (1995) A cytochrome P-450 monooxygenase catalyzes the first step in the conversion of tabersonine to vindoline in Catharanthus roseus. Plant Physiol 109:131ā139. doi:10.1104/pp. 109.1.131
VĆ”zquez-Flota F, De Luca V, Carrillo-Pech M, Canto-Flick A, Miranda-Ham ML (2002) Vindoline biosynthesis is transcriptionally blocked in Catharanthus roseus cell suspension cultures. Mol Biotechnol 22:1ā8. doi:10.1385/MB:22:1:001
Aerts RJ, De Luca V (1992) Phytochrome is involved in the light-regulation of vindoline biosynthesis in Catharanthus roseus. Plant Physiol 100:1029ā1032. doi:0032-0889/92/100/1029/04/$01.00/0
Aerts R, Gisi D, De Carolis E, De Luca V, Baumann TW (1994) Methyl jasmonate vapor increases the developmentally controlled synthesis of alkaloids in Catharanthus and Cinchona seedlings. Plant J 5:635ā643. doi:10.1111/j.1365-313X.1994.00635.x
Sottomayor M, Ros BarcelĆ³ A (2003) Peroxidase from Catharanthus roseus (L.) G. Don and the biosynthesis of Ī±-3ā²,4ā²-anhydrovinblastine: a specific role for a multifunctional enzyme. Protoplasma 222:97ā105. doi:10.1007/s00709-003-0003-9
Costa MMR, Hilliou F, Duarte P, Pereira LG, Almeida I, Leech M, Memelink J, Ros BarcelĆ³ A, Sottomayor M (2008) Molecular cloning and characterization of a vacuolar class III peroxidase involved in the metabolism of anticancer alkaloids in Catharanthus roseus. Plant Physiol 146:403ā417. doi:10.1104/pp. 107.107060
St-Pierre B, Vazquez-Flota FA, De Luca V (1999) Multicellular compartmentation of Catharanthus roseus alkaloid biosynthesis predicts intercellular translocation of a pathway intermediate. Plant Cell 11:887ā900. doi:10.1105/tpc.11.5.887
Sottomayor M, Lopes Cardoso I, Pereira LG, Ros BarcelĆ³ A (2004) Peroxidase and the biosynthesis of terpenoid indole alkaloids in the medicinal plant Catharanthus roseus (L.) G. Don. Phytochem Rev 3:159ā171. doi:10.1023/B:PHYT.0000047807.66887.09
Verpoorte R, Contin A, Memelink J (2002) Biotechnology for production of plant secondary metabolites. Phytochem Rev 1:13ā25. doi:10.1023/A:1015871916833
Zhao J, Verpoorte R (2007) Manipulating indole alkaloid production by Catharanthus roseus cell cultures in bioreactors: from biochemical processing to metabolic engineering. Phytochem Rev 6:435ā457. doi:10.1007/s11101-006-9050-0
Deus B, Zenk MH (1982) Exploitation of plant cells for the production of natural compounds. Biotechnol Bioeng 24:1965ā1974. doi:10.1002/bit.260240905
Kurz WGW, Chatson KB, Constabel F (1985) Biosynthesis and accumulation of indole alkaloids in cell suspension cultures of Catharanthus roseus cultivars. In: Neumann KH, Barz W, Reinhard E (eds) Primary and secondary metabolism of plant cell cultures. Springer-Verlag, Berlin, pp 143ā153
Naaranlahti T, Ranta VP, Jarho P, Nordstrom M, Lapinjoki SP (1989) Electrochemical detection of indole alkaloids of Catharanthus roseus in high-performance liquid chromatography. Analyst 114:1229ā1231. doi:10.1039/AN9891401229
Ganapathi B, Kargi F (1990) Recent advances in indole alkaloid production by Catharanthus roseus (Periwinkle). J Exp Bot 41:259ā267. doi:10.1093/jxb/41.3.259
Shukla AK, Shasany AK, Verma RK, Gupta MM, Mathur AK, Khanuja PSP (2010) Influence of cellular differentiation and elicitation on intermediate and late steps of terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Protoplasma 24:35ā47. doi:10.1007/s00709-010-0120-1
Endo T, Goodbody AE, Misawa M (1987) Alkaloid production in root and shoot cultures of Catharanthus roseus. Planta Med 53:479ā482. doi:10.1055/s-2006-962777
OāKeefe BR, Mahady GB, Gills JJ, Beecher CWW (1997) Stable vindoline production in transformed cell cultures of Catharanthus roseus. J Nat Prod 60:261ā264. doi:10.1021/np960703n
Miura Y, Hirata K, Kurano N, Miyamoto K, Uchida K (1988) Formation of vinblastine in multiple shoot culture of Catharanthus roseus. Planta Med 54:18ā20. doi:10.1055/s-2006-962321
Bhadra R, Vani S, Shanks JV (1993) Production of indole alkaloids by selected hairy root lines of Catharanthus roseus. Biotechnol Bioeng 41:581ā592. doi:10.1002/bit.260410511
Jung KH, Kwak SS, Choi CY, Liu JR (1995) An interchangeable system of hairy root and cell suspension cultures of Catharanthus roseus for indole alkaloid production. Plant Cell Rep 15:51ā54. doi:10.1007/BF01690252
PalazĆ³n J, CusidĆ³ RM, Gonzalo J, Bonfill M, Morales C, Pinol T (1998) Relation between the amount of rolC gene product and indole alkaloid accumulation in Catharanthus roseus transformed root cultures. J Plant Physiol 153:712ā718. doi:35400007196000.0270
Binder BYK, Peebles CAM, Shanks JV, San KY (2009) The effects of UV-B stress on the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots. Biotechnol Prog 25:861ā865. doi:10.1002/btpr.97
Pan QF, Chen Y, Wang Q, Yuan F, Xing SH, Tian YS, Zhao JY, Sun XF, Tang KX (2010) Effect of plant growth regulators on the biosynthesis of vinblastine, vindoline and catharanthine in Catharanthus roseus. Plant Growth Reg 60:133ā141. doi:10.1007/s10725-009-9429-1
Peebles C, Sander GW, Hughes EH, Peacock R, Shanks JV, San KY (2011) The expression of 1-deoxy-D-xylulose synthase and geraniol-10-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots. Metab Eng 13:234ā240. doi:10.1016/j.ymben.2010.11.005
Tang KX, Liu DH, Wang YL, Cui LJ, Ren WW, Sun XF (2011) Overexpression of transcriptional factor ORCA3 increases the accumulation of catharanthine and vindoline in Catharanthus roseus hairy roots. Rus J Plant Physiol 58:415ā422. doi:10.1134/S1021443711030125
van der Heijden R, Verpoorte R, ten Hoopen HJG (1989) Cell and tissue cultures of Catharanthus roseus (L.) G. Don: a literature survey. Plant Cell Tiss Org Cult 18:231ā280. doi:10.1007/BF00043397
Zhao J, Hu Q, Guo YQ, Zhu WH (2001) Effects of stress factors, bioregulators, and synthetic precursors on indole alkaloid production in compact callus clusters cultures of Catharanthus roseus. Appl Microbiol Biotechnol 55:693ā698. doi:10.1007/s002530000568
Schlatmann JE, Koolhaas CMA, Vinke JL, ten Hoopen HJG, Heijnen JJ (1995) The role of glucose in ajmalicine production by Catharanthus roseus cell cultures. Biotechnol Bioeng 47:525ā534. doi:10.1002/bit.260470504
Zhao J, Zhu WH, Hu Q, He XW (2001) Enhanced indole alkaloid production in suspension compact callus clusters of Catharanthus roseus: impacts of plant growth regulators and sucrose. Plant Growth Reg 33:33ā41. doi:10.1023/A:1010732308175
Jung KH, Kwak SS, Kim SW, Lee H, Choi CY, Liu JR (1992) Improvement of the catharanthine productivity in hairy root cultures of Catharanthus roseus by using monosaccharides as a carbon source. Biotechnol Lett 14:695ā700. doi:10.1007/BF01021645
Almagro L, LĆ³pez-PĆ©rez AJ, PedreƱo MA (2010) New method to enhance ajmalicine production in Catharanthus roseus cell cultures based on the use of cyclodextrins. Biotechnol Lett 33:381ā385. doi:10.1007/s10529-010-0430-6
Lee CWT, Shuler ML (2000) The effect of inoculum density and conditioned medium on the production of ajmalicine and catharanthine from immobilized Catharanthus roseus cells. Biotechnol Bioeng 67:61ā71. doi:10.1002/(SICI)1097-0290(20000105)67:1<61::AID-BIT7>3.0.CO;2-J
Whitmer S, Verpoorte R, Canel C (1998) Influence of auxins on alkaloid accumulation by a transgenic cell line of Catharanthus roseus. Plant Cell Tissue Organ Cult 53:135ā141. doi:10.1104/pp. 116.2.853
El-Sayed M, Verpoorte R (2002) Effect of phytohormones on growth and alkaloid accumulation by a Catharanthus roseus cell suspension cultures fed with alkaloid precursors tryptamine and loganin. Plant Cell Tiss Organ Cult 68:265ā270. doi:10.1023/A:1013968826635
Zhao J, Zhu WH, Hu Q (2001) Effects of light and plant growth regulators on the biosynthesis of vindoline and other indole alkaloids in Catharanthus roseus callus cultures. Plant Growth Reg 33:43ā49. doi:10.1023/A:1010722925013
Satdive RK, Fulzele DP, Eapen S (2003) Studies on production of ajmalicine in shake flasks by multiple shoot cultures of Catharanthus roseus. Biotechnol Prog 19:1071ā1075. doi:10.1021/bp020138g
Lee CWT, Shuler ML (1991) Different shake flask closures alter gas phase composition and ajmalicine production in Catharanthus roseus cell suspensions. Biotechnol Technol 5:173ā178. doi:10.1007/BF00152776
Lee-Parson CWT, Shuler ML (2005) Sparge gas composition affects biomass and ajmalicine production from immobilized cell cultures of Catharanthus roseus. Enzyme MicrobTechnol 37:424ā434. doi:10.1016/j.enzmictec.2005.02.016
El-Sayed M, Choi YH, FrĆ©derichrich M, Roytrakul S, Verpoorte R (2004) Alkaloid accumulation in Catharanthus roseus cell suspension cultures fed with stemmadenine. Biotechnol Lett 26:793ā798. doi:10.1023/B:BILE.0000025879.53632.f2
Zhao J, Zhu WH, Hu Q (2000) Enhanced ajmalicine production in Catharanthus roseus cell cultures by combined elicitor treatment: from shake-flask to 20-l airlift bioreactor. Biotechnol Lett 22:509ā514. doi:10.1023/A:1005616920165. doi:10.1023/A:1005616920165
Morgan JA, Shanks JV (2000) Determination of metabolic rate-limitations by precursor feeding in Catharanthus roseus hairy root cultures. J Biotechnol 79:137ā145. doi:10.1016/S0168-1656(00)00221-2
Asada M, Shuler ML (1989) Stimulation of ajmalicine production and excretion from Catharanthus roseus: effects of adsorption in situ, elicitors, and alginate immobilization. Appl Microbiol Biotechnol 30:475ā481. doi:10.1007/BF00263851
Lee-Parsons CWT, ErtĆ¼rk S, Tengtrakool J (2004) Enhancement of ajmalicine production in Catharanthus roseus cell cultures with MeJa is dependent on timing and dosage of elicitation. Biotechnol Lett 26:1595ā1599. doi:10.1023/B:BILE.0000045825.37395.94
Xu MJ, Dong JF (2005) Effect of nitric oxide on catharanthine production and growth of Catharanthus roseus suspension cells. Biotechnol Bioeng 89:367ā371. doi:10.1002/bit.20334
Godoy-HernĆ”ndez GC, Loyola-Vargas VM (1997) Effect of acetylsalicylic acid on secondary metabolism of Catharanthus roseus tumor suspension cultures. Plant Cell Rep 16:287ā290. doi:10.1007/BF01088282
Ramani S, Jayabaskaran C (2008) Enhanced catharanthine and vindoline production in suspension cultures of Catharanthus roseus by ultraviolet-B light. J Mol Signal 3:9ā14. doi:10.1186/1750-2187-3-9
Almagro L, Sabater-Jara AB, Belchi-Navarro S, Fernandez-Perez F, Bru R, PedreƱo MA (2011) Effect of UV light on secondary metabolite biosynthesis in plant cell cultures elicited with cyclodextrins and methyljasmonate. Plants and environment, 1st edn. Intech, Croatia
Godoy-HernĆ”ndez GC, VĆ”zquez-Flota FA, Loyola-Vargas VM (2000) The exposure to trans-cinnamic acid of osmotically stressed Catharanthus roseus cells cultured in a 14-L bioreactor increases alkaloid accumulation. Biotechnol Lett 22:921ā925. doi:10.1023/A:1005672400219
Smith JI, Smart NJ, Kurz WGW, Misawa M (1987) The use of organic and inorganic compounds to increase the accumulation of indole alkaloids in Catharanthus roseus (L.) G. Don cell suspension cultures. J Exp Bot 38:1501ā1506. doi:10.1093/jxb/38.9.1501
Oksman-Caldentey KM, InzĆ© D (2004) Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. Trends Plant Sci 9:1360ā1385. doi:10.1016/j.tplants.2004.07.006
SchƤfer H, Wink M (2009) Medicinally important secondary metabolites in recombinant microorganisms or plants: progress in alkaloid biosynthesis. Biotechnol J 4:1684ā1703. doi:10.1002/biot.200900229
ZĆ”rate R, Verpoorte R (2007) Strategies for the genetic modification of the medicinal plant Catharanthus roseus (L.) G. Don. Phytochem Rev 6:475ā491. doi:10.1007/s11101-006-9020-6
Lorence A, Verpoorte R (2004) Gene transfer and expression in plants. Methods Mol Biol 267:329ā350. doi:10.1385/1-59259-774-2:329
Whitmer S, van der Heijden R, Verpoorte R (2002) Effect of precursor feeding on alkaloid accumulation by a tryptophan decarboxylase over-expressing transgenic cell line T22 of Catharanthus roseus. J Biotechnol 96:193ā203. doi:10.1016/S0168-1656(02)00027-5
Wang CT, Liu H, Gao XS, Zhang HX (2010) Overexpression of G10H and ORCA3 in the hairy roots of Catharanthus roseus improves catharanthine production. Plant Cell Rep 29:887ā894. doi:10.1007/s00299-010-0874-0
Jaggi M, Kumar S, Sinha AK (2011) Overexpression of an apoplastic peroxidase gene CrPrx in transgenic hairy root lines of Catharanthus roseus. Appl Microbiol Biotechnol 90:1005ā1016. doi:10.1007/s00253-011-3131-8
Magnotta M, Murata J, Chen J, De Luca V (2007) Expression of deacetylvindoline-4-O-acetyltransferase in Catharanthus roseus hairy roots. Phytochemistry 68:1922ā1931. doi:10.1016/j.phytochem.2007.04.037
van der Fits L, Memelink J (2000) ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. Science 289:295ā297. doi:10.1126/science.289.5477.295
Peebles C, Hughes EH, Jacqueline V, Shanks SKY (2009) Transcriptional response of the terpenoid indole alkaloid pathway to the overexpression of ORCA3 along with jasmonic acid elicitation of Catharanthus roseus hairy roots over time. Metab Eng 11:76ā86. doi:10.1016/j.ymben.2008.09.002
Hallard D, van der Heijden R, Verpoorte R, Lopez-Cardoso I, Pasquali G, Memelink J, Hoge JHC (1997) Suspension cultured transgenic cells of Nicotiana tabacum expressing tryptophan decarboxylase and strictosidine synthase cDNAs from Catharanthus roseus produce strictosidine upon feeding of secologanin. Plant Cell Rep 17:50ā54. doi:10.1007/s002990050350
Hallard D (2000) Transgenic plant cells for the production of indole alkaloids. Ph.D.-thesis, Leiden University, ISBN 90-74538-49-5
Geerlings A, Hallard D, Caballero AM, Cardoso IL (1999) Alkaloid production by a Cinchona officinalis āLedgerianaā hairy root culture containing constitutive expression constructs of tryptophan decarboxylase and strictosidine synthase cDNAs from Catharanthus roseus. Plant Cell Rep 19:191ā196. doi:10.1007/s002990050732
Geerlings A, Redondo FJ, Contin A, Memelink J, van der Heijden R, Verpoorte R (2001) Biotransformation of tryptamine and secologanin into plant terpenoid indole alkaloids by transgenic yeast. Appl Microbiol Biotechnol 56:420ā424. doi:10.1007/s002530100663
Shen ZQ, Eisenreich W, Kutchan TM (1998) Bacterial biotransformation of 3 alpha(S)-strictosidine to the monoterpenoid indole alkaloid vallesiachotamine. Phytochemistry 48:293ā296. doi:10.1016/S0031-9422(97)01116-3
Acknowledgments
This study was supported by the FundaciĆ³n SĆ©neca, Agencia de Ciencia y TecnologĆa de la RegiĆ³n de Murcia en el marco de II PCTRM 2007-10 (08799/PI/08). We are also grateful to the European Cooperation in the field of Scientific and Technical Research (Cost Action FA1006). Almagro L. has a grant from the Ministerio de Ciencia e InnovaciĆ³n.
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Almagro, L., Sottomayor, M., Angeles PedreƱo, M. (2013). Bioproduction of Terpenoid Indole Alkaloids from Catharanthus roseus Cell Cultures. In: Ramawat, K., MƩrillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_4
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DOI: https://doi.org/10.1007/978-3-642-22144-6_4
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Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-22143-9
Online ISBN: 978-3-642-22144-6
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