Advertisement

Hairy Roots pp 71-93 | Cite as

Biotechnological Interventions of Hairy Roots of Tropane Alkaloid-Bearing Plants

  • Guoyin KaiEmail author
  • Weiwei Zhao
  • Min Shi
  • Yao Wang
Chapter

Abstract

As one large group of plant secondary metabolites, tropane alkaloids (TAs) can be produced by a few genera of the family Solanaceae including Anisodus, Atropa, Datura, Hyoscyamus, and Scopolia. Due to their anti-cholinergic activity, tropane alkaloids including hyoscyamine and scopolamine are widely used as antispasmodics and mydriatics. Because of low contents in tropane alkaloid-bearing plants, it is urgent to elevate the production of tropane alkaloids by means of biotechnology approaches to meet the increasing clinical demand. Hairy roots, with the characters of fast-growing, auxin-independent, and genetically stable, were considered as a promising system to produce active plant-origin compounds including tropane alkaloids. Recently, hairy root systems of some tropane alkaloid-producing plants such as Anisodus acutangulus have been successfully established. Meanwhile, several key enzymes involved in the TAs biosynthetic pathway have been cloned and introduced into related genetic engineered hairy root systems, which lay the foundation for production of tropane alkaloids in hairy roots by large-scale bioreactors in the future. Here, the recent advances of pharmacological activity, hairy root, biosynthesis pathway, and genetic engineering were summarized, and problems along with prospects were also discussed.

Keywords

Solanaceae Tropane alkaloids Hairy roots Biosynthesis pathway Metabolic engineering 

Notes

Acknowledgments

This work was supported by the National Natural Science Fund (31270007, 81522049, 31571735), Zhejiang Provincial Key University Project on the Construction of First-class Subjects, Shanghai Science and Technology Committee Project (17JC1404300, 15430502700), New Century Talent Project (NECT-13-0902), the “Dawn” Program of Shanghai Education Commission (16SG38), and Shanghai Engineering Research Center of Plant Germplasm Resources (17DZ2252700).

References

  1. Altabella T, Palazón J, Ribó M, Angel E, Pifiol MT (1994) Comparative study of tropane alkaloid production in transformed roots of Datura stramonium and Scopolia carniolica. Plant Physiol 13:113–123Google Scholar
  2. Bedewitz MA, Góngora-Castillo E, Uebler JB, Gonzales-Vigil E, Wiegert-Rininger KE, Childs KL, DellaPenna D (2014) A root-expressed L-phenylalanine: 4-hydroxyphenylpyruvate aminotransferase is required for tropane alkaloid biosynthesis in Atropa belladonna. Plant Cell 26(9):3745–3762PubMedPubMedCentralCrossRefGoogle Scholar
  3. Boitel-Conti M, Laberche JC, Lanoue A, Ducrocq C, Sangwan-Norreel BS (2000) Influence of feeding precursors on tropane alkaloid production during an abiotic stress in Datura innoxia transformed roots. Plant Cell Tissue Organ Cult 60(2):131–137CrossRefGoogle Scholar
  4. Bonhomme V, Laurain-Mattar D, Lacoux J, Fliniaux MA, Jacquin-Dubreuil A (2000) Tropane alkaloid production by hairy roots of Atropa belladonna obtained after transformation with Agrobacterium rhizogenes 15834 and agrobacterium tumefaciens containing rolA, B, C genes only. J Biotechnol 81(2):151–158PubMedCrossRefGoogle Scholar
  5. Cardillo AB, Giulietti AM, Palazón J, Bonfill M (2013) Influence of hairy root ecotypes on production of tropane alkaloids in Brugmansia candida. Plant Cell Tissue Organ Cult 114(3):305–312CrossRefGoogle Scholar
  6. Chen J, Dong X, Li Q, Zhou X, Gao S, Chen R, Chen W (2013) Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling. BMC Genomics 14(1):857PubMedPubMedCentralCrossRefGoogle Scholar
  7. Christen P, Roberts MF, Phillipson JD, Evans WC (1989) High-yield production of tropane alkaloids by hairy-root cultures of Datura candida hybrid. Plant Cell Rep 8(2):75–77PubMedCrossRefGoogle Scholar
  8. Christen P, Aoki T, Shimomura K (1992) Characteristics of growth and tropane alkaloid production in Hyoscyamus albus hairy roots transformed with Agrobacterium rhizogenes A4. Plant Cell Rep 11(12):597–600PubMedCrossRefPubMedCentralGoogle Scholar
  9. Cui L, Huang F, Zhang D, Lin Y, Liao P, Zong J, Kai G (2015) Transcriptome exploration for further understanding of the tropane alkaloids biosynthesis in Anisodus acutangulus. Mol Gen Genomics 290(4):1367–1377CrossRefGoogle Scholar
  10. Dechaux C, Boitel-Conti M (2005) A strategy for overaccumulation of scopolamine in Datura innoxia hairy root cultures. Acta Biol Cracov Ser Bot 47:101–107Google Scholar
  11. Dehghan E, Reed DW, Covello PS, Hasanpour Z, Palazon J, Oksman-Caldentey KM, Ahmadi FS (2017) Genetically engineered hairy root cultures of Hyoscyamus senecionis and H. muticus: ploidy as a promising parameter in the metabolic engineering of tropane alkaloids. Plant Cell Rep 36(10):1615–1626PubMedCrossRefGoogle Scholar
  12. Deno H, Yamagata H, Emoto T, Yoshioka T, Yamada Y, Fujita Y (1987) Scopolamine production by root cultures of Duboisia myoporoides: II. Establishment of a hairy root culture by infection with Agrobacterium rhizogenes. J Plant Physiol 131(3–4):315–323CrossRefGoogle Scholar
  13. Dräger B (2006) Tropinone reductases, enzymes at the branch point of tropane alkaloid metabolism. Phytochemistry 67(4):327–337PubMedCrossRefGoogle Scholar
  14. Ebel J (1998) Oligoglucoside elicitor-mediated activation of plant defense. BioEssays 20(7):569–576PubMedCrossRefGoogle Scholar
  15. Eisenkraft A, Falk A (2016) Possible role for anisodamine in organophosphate poisoning. Br J Pharmacol 173(11):1719–1727PubMedPubMedCentralCrossRefGoogle Scholar
  16. El Jaber-Vazdekis N, Barres ML, Ravelo AG, Zárate R (2008) Effects of elicitors on tropane alkaloids and gene expression in Atropa baetica transgenic hairy roots. J Nat Prod 71(12):2026–2031PubMedCrossRefPubMedCentralGoogle Scholar
  17. Georgiev MI, Weber J (2014) Bioreactors for plant cells: hardware configuration and internal environment optimization as tools for wider commercialization. Biotechnol Lett 36(7):1359–1367PubMedCrossRefPubMedCentralGoogle Scholar
  18. Guillon S, Trémouillaux-Guiller J, Pati PK, Rideau M, Gantet P (2006) Hairy root research: recent scenario and exciting prospects. Curr Opin Plant Biol 9(3):341–346PubMedCrossRefGoogle Scholar
  19. Häkkinen ST, Moyano E, Cusidó RM, Palazón J, Piñol MT, Oksman-Caldentey KM (2005) Enhanced secretion of tropane alkaloids in Nicotiana tabacum hairy roots expressing heterologous hyoscyamine-6β-hydroxylase. J Exp Bot 420:2611–2618CrossRefGoogle Scholar
  20. Hao X, Shi M, Cui L, Xu C, Zhang Y, Kai G (2015) Effects of methyl jasmonate and salicylic acid on tanshinone production and biosynthetic gene expression in transgenic Salvia miltiorrhiza hairy roots. Biotechnol Appl Biochem 62(1):24–31PubMedCrossRefGoogle Scholar
  21. Hashimoto T, Nakajima K, Ongena G, Yamada Y (1992) Two tropinone reductases with distinct stereospecificities from cultured roots of Hyoscyamus niger. Plant Physiol 100(2):836–845PubMedPubMedCentralCrossRefGoogle Scholar
  22. Heim WG, Sykes KA, Hildreth SB, Sun J, Lu RH, Jelesko JG (2007) Cloning and characterization of a Nicotiana tabacum methylputrescine oxidase transcript. Phytochemistry 68(4):454–463PubMedCrossRefGoogle Scholar
  23. Hibi N, Higashiguchi S, Hashimoto T, Yamada Y (1994) Gene expression in tobacco low-nicotine mutants. Plant Cell 6(5):723–735PubMedPubMedCentralCrossRefGoogle Scholar
  24. Huang F, Dai XD, Hu YL, Chen CY, Zhu GZ (2005) Progress in synthesis of tropane alkaloids. Chem Reagent 27:141–144Google Scholar
  25. Jaremicz Z, Luczkiewicz M, Kokotkiewicz A, Krolicka A, Sowinski P (2014) Production of tropane alkaloids in Hyoscyamus niger (black henbane) hairy roots grown in bubble-column and spray bioreactors. Biotechnol Lett 36(4):843–853PubMedCrossRefGoogle Scholar
  26. Jirschitzka J, Dolke F, d’Auria JC (2013) Increasing the pace of new discoveries in tropane alkaloid biosynthesis. Adv Bot Res 68:39–72CrossRefGoogle Scholar
  27. Jouhikainen K, Lindgren L, Jokelainen T, Hiltunen R, Teeri TH, Oksman-Caldentey KM (1999) Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. Planta 208(4):545–551CrossRefGoogle Scholar
  28. Kai G, Chen J, Li L, Zhou G, Zhou L, Zhang L, Zhao L (2007) Molecular cloning and characterization of a new cDNA encoding hyoscyamine 6β-hydroxylase from roots of Anisodus acutangulus. BMB Rep 40(5):715–722CrossRefGoogle Scholar
  29. Kai G, Li L, Jiang Y, Yan X, Zhang Y, Lu X, Chen J (2009a) Molecular cloning and characterization of two tropinone reductases in Anisodus acutangulus and enhancement of tropane alkaloid production in AaTRI-transformed hairy roots. Biotechnol Appl Biochem 54(3):177–186PubMedCrossRefPubMedCentralGoogle Scholar
  30. Kai G, Zhang Y, Chen J, Li L, Yan X, Zhang R, Zhou G (2009b) Molecular characterization and expression analysis of two distinct putrescine N-methyltransferases from roots of Anisodus acutangulus. Physiol Plant 135(2):121–129PubMedCrossRefPubMedCentralGoogle Scholar
  31. Kai G, Yang S, Luo X, Zhou W, Fu X, Zhang A, Xiao J (2011) Co-expression of AaPMT and AaTRI effectively enhances the yields of tropane alkaloids in Anisodus acutangulus hairy roots. BMC Biotechnol 11(1):43PubMedPubMedCentralCrossRefGoogle Scholar
  32. Kai G, Zhang A, Guo Y, Li L, Cui L, Luo X, Xiao J (2012) Enhancing the production of tropane alkaloids in transgenic Anisodus acutangulus hairy root cultures by over-expressing tropinone reductase I and hyoscyamine-6β-hydroxylase. Mol BioSyst 8(11):2883–2890PubMedCrossRefPubMedCentralGoogle Scholar
  33. Kaiser H, Richter U, Keiner R, Brabant A, Hause B, Dräger B (2006) Immunolocalisation of two tropinone reductases in potato (Solanum tuberosum L.) root, stolon, and tuber sprouts. Planta 225(1):127–137PubMedCrossRefPubMedCentralGoogle Scholar
  34. Kamada H, Okamura N, Satake M, Harada H, Shimomura K (1986) Alkaloid production by hairy root cultures in Atropa belladonna. Plant Cell Rep 5(4):239–242PubMedCrossRefPubMedCentralGoogle Scholar
  35. Kang YM, Park DJ, Min JY, Song HJ, Jeong MJ, Kim YD, Choi MS (2011) Enhanced production of tropane alkaloids in transgenic Scopolia parviflora hairy root cultures over-expressing putrescine N-methyl transferase (PMT) and hyoscyamine-6β-hydroxylase (H6H). In Vitro Cell Dev-Pl 47(4):516–524CrossRefGoogle Scholar
  36. Katoh A, Shoji T, Hashimoto T (2007) Molecular cloning of N-methylputrescine oxidase from tobacco. Plant Cell Physiol 48(3):550–554PubMedCrossRefPubMedCentralGoogle Scholar
  37. Kholodenko BN, Cascante M, Hoek JB, Westerhoff HV, Schwaber J (1998) Metabolic design: how to engineer a living cell to desired metabolite concentrations and fluxes. Biotechnol Bioeng 59(2):239–247PubMedCrossRefPubMedCentralGoogle Scholar
  38. Knopp E, Strauss A, Wehrli W (1988) Root induction on several Solanaceae species by Agrobacterium rhizogenes and the determination of root tropane alkaloid content. Plant Cell Rep 7(7):590–593PubMedCrossRefGoogle Scholar
  39. Koumis T, Samuel S (2005) Tiotropium bromide: a new long-acting bronchodilator for the treatment of chronic obstructive pulmonary disease. Clin Ther 27(4):377–392PubMedCrossRefGoogle Scholar
  40. Kutchan TM (1995) Alkaloid biosynthesis-the basis for metabolic engineering of medicinal plants. Plant Cell 7(7):1059–1070PubMedPubMedCentralGoogle Scholar
  41. Lei TX, Cai XJ, Wang H, Li SL, Sheng JW, Zhou DW (2016) Progress on molecular mechanism of tropane alkaloids synthesis and plant bioengineering research. Acta Botan Boreali-Occiden Sin 36(1):204–214Google Scholar
  42. Li R, Reed DW, Liu E, Nowak J, Pelcher LE, Page JE, Covello PS (2006) Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement. Chem Biol 13(5):513–520PubMedCrossRefGoogle Scholar
  43. Li L, Wang J, Wang W, Lu Y, Wang Y, Zhou G, Kai G (2008) Optimization of induction and culture conditions and tropane alkaloid production in hairy roots of Anisodus acutangulus. Biotechnol Bioproc E 13(5):606–612CrossRefGoogle Scholar
  44. Liu (2016) Influence and preliminary mechanism of elicitors on growth and tropane alkaloids in hairy roots of Atropa belladonna L. Southwest UniversityGoogle Scholar
  45. Liu T, Zhu P, Meng C, Zhu HX (2005) Molecular cloning and expression of putrescine N-methyltransferase from the hairy roots of Anisodus tanguticus. Planta Med 71(10):987–989PubMedCrossRefGoogle Scholar
  46. Liu WD, Chen LL, Shen CY, Jiang LB (2015) Neuroprotective effect of compound anisodine in a mouse model with chronic ocular hypertension. Chin Med J 128(19):2652–2657PubMedPubMedCentralCrossRefGoogle Scholar
  47. Lu BB, Zhang L, Kai GY, Zhang HM, Ding RX, Chen WS (2005) Establishment of hairy root culture of Hyoscyamus niger. Chin Tradit Herb Drug 36(12):1864Google Scholar
  48. Maldonado-Mendoza IE, Loyola-Vargas VM (1995) Establishment and characterization of photosynthetic hairy root cultures of Datura stramonium. Plant Cell Tissue Organ Cult 40(3):197–208CrossRefGoogle Scholar
  49. Maldonado-Mendoza IE, Ayora-Talavera T, Loyola-Vargas VM (1993) Establishment of hairy root cultures of Datura stramonium. Characterization and stability of tropane alkaloid production during long periods of subculturing. Plant Cell Tissue Organ Cult 33(3):321–329CrossRefGoogle Scholar
  50. Mano Y, Nabeshima S, Matsui C, Ohkawa H (1986) Production of tropane alkaloids by hairy root cultures of Scopolia japonica. Agric Biol Chem 50(11):2715–2722Google Scholar
  51. Marín-Sáez J, Romero-González R, Frenich AG (2017) Multi-analysis determination of tropane alkaloids in cereals and solanaceaes seeds by liquid chromatography coupled to single stage Exactive-Orbitrap. J Chromatogr A 1518:46–58PubMedCrossRefGoogle Scholar
  52. Matsuda J, Okabe S, Hashimoto T, Yamada Y (1991) Molecular cloning of hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger. J Biol Chem 266(15):9460–9464PubMedGoogle Scholar
  53. Mehrotra S, Srivastava V, Rahman LU, Kukreja AK (2015) Hairy root biotechnology—indicative timeline to understand missing links and future outlook. Protoplasma 252(5):1189–1201PubMedCrossRefGoogle Scholar
  54. Meng C, Zuo X, Wang L (2002) Production of scopolamine by hair root cultures of Anisodas tanguticus. Nat Prod Res Dev 14(1):21–24Google Scholar
  55. Mishra BN, Ranjan R (2008) Growth of hairy-root cultures in various bioreactors for the production of secondary metabolites. Biotechnol Appl Biochem 49(1):1–10PubMedCrossRefGoogle Scholar
  56. Moharrami F, Hosseini B, Sharafi A, Farjaminezhad M (2017) Enhanced production of hyoscyamine and scopolamine from genetically transformed root culture of Hyoscyamus reticulatus L. elicited by iron oxide nanoparticles. In Vitro Cell Dev-Pl 53(2):104–111CrossRefGoogle Scholar
  57. Moyano E, Fornalé S, Palazón J, Cusidó RM, Bagni PMT (2002) Alkaloid production in Duboisia hybrid hairy root cultures overexpressing the pmt gene. Phytochemistry 59(7):697–702PubMedCrossRefGoogle Scholar
  58. Munir N, Iqbal AS, Altaf I, Bashir R, Sharif N, Saleem F, Naz S (2014) Evaluation of antioxidant and antimicrobial potential of two endangered plant species atropa belladonna and matricaria chamomilla. Afr J Tradit Complement Altern Med 11(5):111–117PubMedPubMedCentralCrossRefGoogle Scholar
  59. Nakajima K, Hashimoto T, Yamada Y (1993a) cDNA encoding tropinone reductase-II from Hyoscyamus niger. Plant Physiol 103(4):1465–1466PubMedPubMedCentralCrossRefGoogle Scholar
  60. Nakajima K, Hashimoto T, Yamada Y (1993b) Two tropinone reductases with different stereospecificities are short-chain dehydrogenases evolved from a common ancestor. Proc Natl Acad Sci 90(20):9591–9595PubMedCrossRefGoogle Scholar
  61. O’Connor SE (2012) Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus. Methods Enzymol 515:189–206PubMedCrossRefGoogle Scholar
  62. Ono NN, Tian L (2011) The multiplicity of hairy root cultures: prolific possibilities. Plant Sci 180(3):439–446PubMedCrossRefGoogle Scholar
  63. Pan (2006) Molecular characterization of Isopentenyi diphosphate isomerase gene from Camptotheca acuminate and metabolic engineering of tropane alkaloids pathway in Anisodus acutangulus. Southwest UniversityGoogle Scholar
  64. Pitta-Alvarez SI, Spollansky TC, Giulietti AM (2000) The influence of different biotic and abiotic elicitors on the production and profile of tropane alkaloids in hairy root cultures of Brugmansia candida. Enzym Microb Technol 26(2):252–258CrossRefGoogle Scholar
  65. Qiang W, Wang YX, Zhang QZ, Li JD, Xia K, Wu NB, Liao ZH (2014) Expression pattern of genes involved in tropane alkaloids biosynthesis and tropane alkaloids accumulation in Atropa belladonna. Chin J Chin Materia Medica 39(1):52–58Google Scholar
  66. Qiang W, Hou YL, Li X, Xia K, Liao ZH (2015) Cloning and expression of the key enzyme hyoscyamine 6 beta-hydroxylase gene (DaH6H) in scopolamine biosynthesis of Datura arborea. Acta Pharm Sin 50(10):1346–1355Google Scholar
  67. Qin B, Ma L, Wang Y, Chen M, Lan X, Wu N, Liao Z (2014) Effects of acetylsalicylic acid and UV-B on gene expression and tropane alkaloid biosynthesis in hairy root cultures of Anisodus luridus. Plant Cell Tissue Organ Cult 117(3):483–490CrossRefGoogle Scholar
  68. Ren ZH, LI L (2003) A review of strategy to enhance the production of secondary metabolites by plant cell culture. Subtrop Plant Sci 3:016Google Scholar
  69. Robins RJ, Parr AJ, Walton NJ (1991) Studies on the biosynthesis of tropane alkaloids in Datura stramonium L. transformed root cultures. Planta 183(2):196–201PubMedCrossRefGoogle Scholar
  70. Robins RJ, Bachmann P, Woolley JG (1994) Biosynthesis of hyoscyamine involves an intramolecular rearrangement of littorine. J Chem Soc Perkin Trans 1(6):615–619CrossRefGoogle Scholar
  71. Shawwal M, Khushtar M, Rahman MA (2017) Protective effect of hydro-alcoholic extract of Salvia haematodes wall root on cognitive functions in scopolamine-induced amnesia in rats. J Trad Compl Med 7(4):471–475CrossRefGoogle Scholar
  72. Shi M, Luo XQ, Ju GH, Yu XH, Hao XL, Huang Q, Xiao JB, Cui LJ, Kai GY (2014) Increased accumulation of the cardio-cerebrovascular disease treatment drug tanshinone in Salvia miltiorrhiza hairy roots by the enzymes 3-hydroxy-3-methylglutaryl CoA reductase and 1-deoxy-d-xylulose 5-phosphate reductoisomerase. Funct Integr Genomics 14(3):603–615PubMedCrossRefGoogle Scholar
  73. Shimomura K, Sauerwein M, Ishimaru K (1991) Tropane alkaloids in the adventitious and hairy root cultures of solanaceous plants. Phytochemistry 30(7):2275–2278CrossRefGoogle Scholar
  74. Smith EF, Townsend CO (1907) A plant-tumor of bacterial origin. Science 25(643):671–673PubMedCrossRefGoogle Scholar
  75. Stiles AR, Liu CZ (2013) Hairy root culture: bioreactor design and process intensification. Adv Biochem Eng Biotechnol 134:91–114PubMedGoogle Scholar
  76. Sun L, Zhang GF, Zhang X, Liu Q, Liu JG, Su DF, Liu C (2012) Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors. Acta Pharmacol Sin 33(6):761–766PubMedPubMedCentralCrossRefGoogle Scholar
  77. Sun JW, Zhang H, Wang FY, Sun YM, Sun M (2013) Effects of methyl jasmonate on accumulation and release of main tropane alkaloids in liquid cultures of Datura stramonium hairy root. Chin J Chin Materia Medica 38(11):1712–1718Google Scholar
  78. Suzuki KI, Yamada Y, Hashimoto T (1999) Expression of Atropa belladonna putrescine N-methyltransferase gene in root pericycle. Plant Cell Physiol 40(3):289–297PubMedCrossRefGoogle Scholar
  79. Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Lao K (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6(5):377–382PubMedCrossRefPubMedCentralGoogle Scholar
  80. Teuber M, Azemi M, Namjoyan F, Meier AC, Wodak A, Brandt W, Drager B (2007) Putrescine N-methyltransferase-a structure-function analysis. Plant Mol Biol 63(6):787–801PubMedCrossRefPubMedCentralGoogle Scholar
  81. Ullrich SF, Averesch NJ, Castellanos L, Choi YH, Rothauer A, Kayser O (2016) Discrimination of wild types and hybrids of Duboisia myoporoides and Duboisia leichhardtii at different growth stages using 1 H NMR-based metabolite profiling and tropane alkaloids-targeted HPLC-MS analysis. Phytochemistry 131:44–56PubMedCrossRefPubMedCentralGoogle Scholar
  82. Varma DR, Yue TL (1986) Adrenoceptor blocking properties of atropine-like agents anisodamine and anisodine on brain and cardiovascular tissues of rats. Br J Pharmacol 87(3):587–594PubMedPubMedCentralCrossRefGoogle Scholar
  83. Vervliet G, Holsters M, Teuchy H, Van Montagu M, Schell J (1975) Characterization of different plaque-forming and defective temperate phages in agrobacterium strains. J Gen Virol 26(1):33–48PubMedCrossRefPubMedCentralGoogle Scholar
  84. Wang JW, Wu JY (2013) Effective elicitors and process strategies for enhancement of secondary metabolite production in hairy root cultures. Adv Biochem Eng Biotechnol 134:55–89PubMedPubMedCentralGoogle Scholar
  85. Wang H, Pan L, Zhang XF (2002) Quantitative analysis of three kinds of tropane alkalids in Hyoscyamus niger L. and Przewalskia tangutica maxim.by HPLC. Northwest Pharm J 17(1):9–10Google Scholar
  86. Wang Q, Gao S, Luo Y, Kang QY (2017) Compound anisodine affects the proliferation and calcium overload of hypoxia-induced rat retinal progenitor cells and brain neural stem cells via the p-ERK1/2/HIF-1α/VEGF pathway. Exp Ther Med 14(1):600–608PubMedPubMedCentralCrossRefGoogle Scholar
  87. Wilhelm BT, Marguerat S, Goodhead I, Bahler J (2010) Defining transcribed regions using RNA-seq. Nat Protoc 5(2):255–266PubMedCrossRefPubMedCentralGoogle Scholar
  88. Wink M, Roberts MF (1998) Alkaloids: biochemistry, ecology, and medicinal applications. Plenum Press, New York, pp 117–145Google Scholar
  89. Wu JY, Shi M (2008) Ultrahigh diterpenoid tanshinone production through repeated osmotic stress and elicitor stimulation in fed-batch culture of Salvia miltiorrhiza hairy roots. Appl Microbiol Biotechnol 78(3):441–448PubMedCrossRefGoogle Scholar
  90. Wu YF, Lü W, Lu Q, Zhang WS (2005) Asymmetric synthesis of anisodine. Chin Chem Lett 16(10):1287–1289Google Scholar
  91. Xia K, Liu X, Zhang Q, Qiang W, Guo J, Lan X, Liao Z (2016) Promoting scopolamine biosynthesis in transgenic Atropa belladonna plants with pmt and h6h overexpression under field conditions. Plant Physiol Biochem 106:46–53PubMedCrossRefGoogle Scholar
  92. Xiao PG, Xia GC, He LY (1973) The occurrence of some important tropane alkakoids in Chinese solanaceous pants. J Integr Plant Biol 15:187–194Google Scholar
  93. Yang CX, Yang YJ, Peng MF, Chen M, Lan XZ, Liao ZH (2006) Establishment of hairy root cultures of Atropa belladonna. J SW Chin Normal Univ 2(33):116–118Google Scholar
  94. Yang CX, Chen M, Zeng LJ, Zhang L, Liu XQ, Lan XZ, Tang KX, Liao Z (2011) Improvement of tropane alkaloids production in hairy root cultures of Atropa belladonna by overexpressing pmt and h6h genes. Plant Omics J 4(1):29–33Google Scholar
  95. Yun DJ, Hashimoto T, Yamada Y (1992) Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition. Proc Natl Acad Sci U S A 89(24):11799–11803PubMedPubMedCentralCrossRefGoogle Scholar
  96. Zayed R, Wink M (2004) Induction of Tropane Alkaloid Formation in Transformed Root Cultures of Brugmansia suaveolens (Solanaceae). Zeitschrift für Naturforschung C 59(11–12):863–867CrossRefGoogle Scholar
  97. Zárate R, el Jaber-Vazdekis N, Medina B, Ravelo AG (2006) Tailoring tropane alkaloid accumulation in transgenic hairy roots of Atropa baetica by over-expressing the gene encoding hyoscyamine 6β-hydroxylase. Biotechnol Lett 28(16):1271–1277PubMedCrossRefGoogle Scholar
  98. Zhang (2010) Study OR improvement of tropane alkaloids of Anisodus acutangulus hairy roots. Shanghai Normol UniversityGoogle Scholar
  99. Zhang L, Ding R, Chai Y, Bonfill M, Moyano E, Oksman-Caldentey KM, Kai G (2004) Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures. Proc Natl Acad Sci USA 101(17):6786–6791PubMedCrossRefGoogle Scholar
  100. Zhang L, Yang B, Lu B, Kai G, Wang Z, Xia Y, Tang K (2007) Tropane alkaloids production in transgenic Hyoscyamus niger hairy root cultures over-expressing putrescine N-methyltransferase is methyl jasmonate-dependent. Planta 225(4):887–896PubMedCrossRefGoogle Scholar
  101. Zhao J, Davis LC, Verpoorte R (2005) Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnol Adv 23(4):283–333PubMedCrossRefGoogle Scholar
  102. Zhao K, Zeng J, Zhao T, Zhang H, Qiu F, Yang C, Liao Z (2017) Enhancing tropane alkaloid production based on the functional identification of Tropine-forming reductase in Scopolia lurida, a Tibetan medicinal plant. Front Plant Sci 8:1745PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.College of PharmacyZhejiang Chinese Medical UniversityHangzhouPeople’s Republic of China
  2. 2.Institute of Plant Biotechnology, College of Life and Environment SciencesShanghai Normal UniversityShanghaiPeople’s Republic of China

Personalised recommendations