Skip to main content
SpringerLink
Log in

Challenges for the Cultivation of Plant Cells on the Example of Hypericum perforatum and Taxus chinensis

  • Reference work entry
  • First Online:
Bioprocessing of Plant In Vitro Systems

Part of the book series: Reference Series in Phytochemistry ((RSP))

  • 960 Accesses

Abstract

Medicinal plants are sustainable bio-factories for valuable active pharmaceutical ingredients (API). They are commonly grown in the field and their extracts have a given combination of constituents. There is some variation due to climate fluctuations and plant diseases (microbial infections), genotypic changes, soil differences, etc. Additionally, fertile agricultural areas are increasingly limited. However, these variations are undesired because they are non-controllable and can affect the batch conformity of a drug significantly. This is a challenge for producers of phyto-pharmaceuticals, and the variations in the API composition are compensated by mixing extracts from various batches to achieve the required continuous quality of an authorized drug. These drawbacks of field cultivation are overcome by well-defined bioreactor-based cultivation. Biomass growth and API production take place under variable but controllable cultivation conditions, resulting in customized extracts. Variation of the cultivation conditions leads to qualitative and/or quantitative changes in the metabolome. During bioreactor cultivation, plant cells tend to stay connected after division, which leads to the formation of aggregates. The size of shear-sensitive plant cell aggregates influenced by hydrodynamic forces resulting from mechanical agitation was often recognized as an intangible parameter, which might be responsible for general variability in plant cell culture processes. To date, however, the bioreactor approach is not often industrially implemented. This chapter provides an overview of the challenges in the cultivation of plant cell systems, briefly illustrated by (i) research on Hypericum perforatum tissue cultures into up-to-date approaches for production of hyperforin and hypericin, possibly functional at a pre-commercial level in the future, and (ii) effects of hydrodynamic mechanical forces on Taxus chinensis submerged cultures for production of paclitaxel.

Abstract

Higher plants are an abundant source of bioactive and pharmaceutically important chemicals including drugs such as morphine, codeine, reserpine, and several alkaloids and steroids [1]. The world market for herbal medicines has reached US $ 60 billion, with annual growth rates of 5–15% [2]. Over 60% of anticancer drugs and 75% of drugs for infectious diseases currently used are made or extracted from natural sources [3]. The increasing demand for tailored phyto-pharmaceuticals with innovative active pharmaceutical ingredients (APIs) and activity profiles, produced by ecologically more sustainable bio-factories, and the significant reductions in biodiversity are driving efforts to find alternative ways of producing high-value plant-derived metabolites under well-defined cultivation conditions [4].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 449.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 599.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sabater-Jara A, Tudela L, López-Pérez A (2010) In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production. Phytochem Rev 9:343–356

    Article  CAS  Google Scholar 

  2. Kartal M (2007) Intellectual property protection in the natural product drug discovery, traditional herbal medicine and herbal medicinal products. Phytother Res 21:113–119

    Article  PubMed  Google Scholar 

  3. Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981−2002. J Nat Prod 66:1022–1037

    Article  CAS  PubMed  Google Scholar 

  4. Georgiev M, Pavlov A, Bley T (2007) Hairy root type plant in vitro systems as sources of bioactive substances. Appl Microbiol Biotechnol 74:1175–1185

    Article  CAS  PubMed  Google Scholar 

  5. Wucherpfennig T, Schilling J, Sieblitz D, Pump M, Schütte K, Wittmann C, Krull R (2012) Improved assessment of aggregate size in Taxus plant cell suspension cultures using laser diffraction. Eng Life Sci 12:595–602

    Article  CAS  Google Scholar 

  6. McDonald K, Jackman A, Hurst S (2001) Characterization of plant suspension cultures using the focused beam reflectance technique. Biotechnol Lett 23:317–324

    Article  CAS  Google Scholar 

  7. Georgiev M, Weber J, Maciuk A (2009) Bioprocessing of plant cell cultures for mass production of targeted compounds. Appl Microbiol Biotechnol 83:809–823

    Article  CAS  PubMed  Google Scholar 

  8. Haberlandt G (1969) Experiments on the culture of isolated plant cells. Bot Rev 35:68–88

    Article  Google Scholar 

  9. Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10:249–268

    Article  CAS  PubMed  Google Scholar 

  10. Hall R (2000) Plant cell culture initiation. Mol Biotechnol 16:161–173

    Article  CAS  PubMed  Google Scholar 

  11. Verpoorte R, Contin A, Memelink J (2002) Biotechnology for the production of plant secondary metabolites. Phytochem Rev 1:13–25

    Article  CAS  Google Scholar 

  12. Srivastava S, Srivastava AK (2007) Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol 27:29–43

    Article  CAS  PubMed  Google Scholar 

  13. Roberts SC (2007) Production and engineering of terpenoids in plant cell culture. Nat Chem Biol 3:387–395

    Article  CAS  PubMed  Google Scholar 

  14. Kolewe ME, Henson MA, Roberts SC (2010) Characterization of aggregate size in Taxus suspension cell culture. Plant Cell Rep 29:485–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kolewe ME, Henson MA, Roberts SC (2011) Analysis of aggregate size as a process variable affecting paclitaxel accumulation in Taxus suspension cultures. Biotechnol Prog:1365–1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hulst AC, Meyer MMT, Breteler H, Tramper J (1989) Effect of aggregate size in cell cultures of Tagetes patula on thiophene production and cell growth. Appl Microbiol Biotechnol 30:18–25

    Article  CAS  Google Scholar 

  17. Edahiro J, Seki M (2006) Phenylpropanoid metabolite supports cell aggregate formation in strawberry cell suspension culture. J Biosci Bioeng 102:8–13

    Article  CAS  PubMed  Google Scholar 

  18. Jianfeng X, Zhiguo S, Pusun F (1998) Suspension culture of compact callus aggregate of Rhodiola sachalinensis for improved salidroside production. Enzym Microb Technol 23:20–27

    Article  CAS  Google Scholar 

  19. Madhusudhan R, Ramachandra Rao S, Ravishankar GA (1995) Osmolarity as a measure of growth of plant cells in suspension cultures. Enzym Microb Technol 17:989–991

    Article  CAS  Google Scholar 

  20. Zhao D, Huang Y, Jin Z, Qu W, Lu D (2003) Effect of aggregate size in cell cultures of Saussurea medusa on cell growth and jaceosidin production. Plant Cell Rep 21:1129–1133

    Article  CAS  PubMed  Google Scholar 

  21. Bolta Ž, Baričevič D, Raspor P (2003) Biomass segregation in sage cell suspension culture. Biotechnol Lett 25(1):61–65

    Article  CAS  PubMed  Google Scholar 

  22. Pépin M, Smith M, Reid J (1999) Application of imaging tools to plant cell culture: relationship between plant cell aggregation and flavonoid production. In Vitro Cell Dev Biol Plant 35:290–295

    Article  Google Scholar 

  23. Fu C, Zhao D, Huang Y, Ma F (2005) Cellular aggregate size as the critical factor for flavonoid production by suspension cultures of Saussurea medusa. Biotechnol Lett 27:91–95

    Article  CAS  PubMed  Google Scholar 

  24. Klemow KM, Bartlow A, Crawford J, Kocher N, Shah J, Ritsick M (2011) Medical attributes of St. John’s wort (Hypericum perforatum). In: Benzie IFF, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press, Boca Raton

    Google Scholar 

  25. Crockett SL, Robson NK (2011) Taxonomy and chemotaxonomy of the genus Hypericum. Med Aromat Plant Sci Biotechnol 5:1–13

    PubMed  PubMed Central  Google Scholar 

  26. Axarlis S, Mentis A, Demetzos C, Mitaku S, Skaltsounis AL, Marselos M, Malamas M (1998) Antiviral in vitro activity of Hypericum perforatum L. extract on the human cytomegalovirus (HCMV). Phytother Res 12:507–511

    Article  Google Scholar 

  27. Greeson JM, Sanford B, Monti DA (2001) St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology 153:402–414

    Article  CAS  PubMed  Google Scholar 

  28. Hofrichter J, Krohn M, Schumacher T, Lange C, Feistel B, Walbroel B, Heinze HJ, Crockett S, Sharbel TF, Pahnke J (2013) Reduced Alzheimer’s disease pathology by St. John’s Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice. Curr Alzheimer Res 10:1057–1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Oliveira AI, Pinho C, Sarmento B, Dias ACP (2016) Neuroprotective activity of Hypericum perforatum and its major components. Front Plant Sci 7:1–15

    Google Scholar 

  30. Laakmann G, Dienel A, Kieser M (1998) Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine 5:435–442

    Article  CAS  PubMed  Google Scholar 

  31. European Medicines Agency Evaluation of Medicines for Human Use (EMEA) (2009) Doc Ref EMA/HMPC/101303/2008

    Google Scholar 

  32. Knishinsky R (1998) The prozac alternative: natural relief from depression with St. John’s Wort, Kava, Ginkgo, 5-HTP, homeopathy, and other alternative therapies. Healing Art Press, Rochester

    Google Scholar 

  33. European Scientific Cooperative on Phytotherapy (ESCOP) (1997) Hyperici herba. Monographs on the medicinal uses of plant drugs. Exeter, UK Accessed 01 Sept 2016. http://escop.com/about-us/

    Google Scholar 

  34. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, Klein S, Rister RS (1998) The complete german commission E monographs – therapeutic guide to herbal medicines. American Botanical Council, Boston, Integrative Medicine Communication, Austin, pp 214–215

    Google Scholar 

  35. Tekel’ová D, Repcák M, Zemková E, Tóth J (2000) Quantitative changes of dianthrones, hyperforin and flavonoids content in the flower ontogenesis of Hypericum perforatum. Planta Med 66:778–780

    Article  PubMed  Google Scholar 

  36. Zobayed SMA, Afreen F, Goto E, Kozai T (2006) Plant-environment interactions: accumulation of Hypericin in dark glands of Hypericum perforatum. Ann Bot 98:793–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Soelberg J, Jørgensen LB, Jäger AK (2007) Hyperforin accumulates in the translucent glands of Hypericum perforatum. Ann Bot 99:1097–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Blumenthal M, Goldberg A, Brinckmann J (2000) Herbal medicine: expanded commission E monographs. American Botanical Council, Newton, Integrative Medicine Communications, Austin, pp 359–366

    Google Scholar 

  39. Meinke MC, Richter H, Kleemann A, Lademann J, Tscherch K, Rohn S, Schempp CM (2015) Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy. J Biomed Opt 20:051013-1-8

    Google Scholar 

  40. Hölscher D, Shroff R, Knop K, Gottschaldt M, Crecelius A, Schneider B, Heckel DG, Schubert US, Svatoš A (2009) Matrix-free UV-laser desorption/ionization (LDI) mass spectrometric imaging at the single-cell level: distribution of secondary metabolites in Arabidopsis thaliana and Hypericum species. Plant J 60:907–918

    Article  PubMed  CAS  Google Scholar 

  41. Barathan M, Mariappan V, Shankar EM, BJJ A, Goh KL, Vadivelu J (2013) Hypericin-photodynamic therapy leads to interleukin-6 secretion by HepG2 cells and their apoptosis via recruitment of BH3 interacting-domain death agonist and caspases. Cell Death Dis 4:e697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Barras A, Boussekey L, Courtade E, Boukherroub R (2013) Hypericin-loaded lipid nanocapsules for photodynamic cancer therapy in vitro. Nanoscale 5:10562–10572

    Article  CAS  PubMed  Google Scholar 

  43. Mannel M (2004) Drug Interactions with St John’s Wort mechanisms and clinical implications. Drug Saf 27:773–797

    Article  CAS  PubMed  Google Scholar 

  44. Borrelli F, Izzo AA (2009) Herb-drug interactions with St John’s wort (Hypericum perforatum): an update on clinical observations. Am Assoc Pharm Sci 11:710–727

    CAS  Google Scholar 

  45. Schempp CM, Lüdtke R, Winghofer B, Simon JC (2000) Effect of topical application of Hypericum perforatum extract (St. John’s wort) on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 16:125–128

    Article  CAS  PubMed  Google Scholar 

  46. Ernst E (2003) Hypericum: the genus Hypericum. Taylor & Francis/CRC Press, London

    Google Scholar 

  47. Seidler-Lożykowska K (2003) Secondary metabolites content of Hypericum sp. in different stages and plant parts. In: Ernst E (ed) Hypericum: the genus Hypericum. Taylor & Francis, London

    Google Scholar 

  48. Odabas MS, Raduğienë J, Camas N, Janulis V, Ivanauskas L, Çırak C (2009) The quantitative effects of temperature and light intensity on hyperforin and hypericins accumulation in Hypericum perforatum L. J Med Plants Res 3:519–525

    CAS  Google Scholar 

  49. Radušienė J, Karpavičienė B, Stanius Ž (2012) Effect of external and internal factors on secondary metabolites accumulation in St. John’s worth. Bot Lithuanica 18:101–108

    Article  Google Scholar 

  50. Sirvent TM, Krasnoff SB, Gibson DM (2003) Induction of hypericins and hyperforins in Hypericum perforatum in response to damage by herbivores. J Chem Ecol 29:2667–2681

    Article  CAS  PubMed  Google Scholar 

  51. Košuth J, Koperdáková J, Tolonen A, Hohtola A, Čellárová E (2003) The content of hypericins and phloroglucinols in Hypericum perforatum L. seedlings at early stage of development. Plant Sci 165:515–521

    Article  CAS  Google Scholar 

  52. Briskin DP, Gawienowski MC (2001) Differential effects of light and nitrogen on production of hypericins and leaf glands in Hypericum perforatum. Plant Physiol Biochem 39:1075–1081

    Article  CAS  Google Scholar 

  53. Raskin I, Ribnicky DM, Komarnytsky S, Ilic N, Poulev A, Borisjuk N, Brinker A, Moreno DA, Ripoll C, Yakoby N, O’Neal JM, Cornwell T, Pastor I, Fridlender B (2002) Plants and human health in the twenty-first century. Trends Biotechnol 20:522–531

    Article  CAS  PubMed  Google Scholar 

  54. Constantine GH, Karchesy J (1998) Note variations in hypericin concentrations in Hypericum perforatum L. and commercial products. Pharm Biol 36:365–367

    Article  CAS  Google Scholar 

  55. Bilia AR, Bergonzi MC, Morgenni F, Mazzi G, Vincieri FF (2001) Evaluation of chemical stability of St. John’s wort commercial extract and some preparations. Int J Pharma 213:199–208

    Article  CAS  Google Scholar 

  56. Bergonzi MC, Bilia AR, Gallori S, Guerrini D, Vincieri FF (2001) Variability in the content of the constituents of Hypericum perforatum L. and some commercial extracts. Drug Dev Ind Pharm 27:491–497

    Article  CAS  PubMed  Google Scholar 

  57. Shah AK, Avery BA, Wyandt CM (2005) Content analysis and stability evaluation of selected commercial preparations of St. John’s wort. Drug Dev Ind Pharm 31:907–916

    Article  CAS  PubMed  Google Scholar 

  58. Nahrstedt A, Butterweck V (2010) Lessons learned from herbal medicinal products: the example of St. John’s Wort. J Nat Prod 73:1015–1021

    Article  CAS  PubMed  Google Scholar 

  59. Fuzzati N, Gabetta N, Strepponi I, Villa F (2001) High-performance liquid chromatography–electrospray ionisation mass spectrometry and multiple mass spectrometry studies of hyperforin degradation products. J Chromatogr A 926:187–198

    Article  CAS  PubMed  Google Scholar 

  60. Verotta L, Appendino G, Belloro E, Bianchi F, Sterner O, Lovati M, Bombardelli E (2002) Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety. J Nat Prod 65:433–438

    Article  CAS  PubMed  Google Scholar 

  61. Ang CY, Hu L, Heinze TM, Cui Y, Freeman JP, Kozak K, Luo W, Liu FF, Mattia A, DiNovi M (2004) Instability of St. John’s Wort (Hypericum perforatum L.) and degradation of Hyperforin in aqueous solutions and functional beverage. J Agric Food Chem 52:6156–6164

    Article  CAS  PubMed  Google Scholar 

  62. Vajs V, Vugdelija S, Trifunovic S, Karadzić I, Juranić N, Macura S, Milosavljević S (2003) Further degradation product of hyperforin from Hypericum perforatum (St. John’s Wort). Fitoterapia 74:439–444

    Article  CAS  PubMed  Google Scholar 

  63. Draves AH, Walker SE (2000) Determination of hypericin and pseudohypericin in pharmaceutical preparations by liquid chromatography with fluorescence detection. J Chromatogr B 749:57–66

    Article  CAS  Google Scholar 

  64. Wurglics M, Westerhoff K, Kaunzinger A, Wilke A, Baumeister A, Dressman J, Schubert-Zsilavecz M (2001) Batch-to-batch reproducibility of St. John’s wort preparations. Pharmacopsychiatry 34(Suppl 1):152–156

    Article  Google Scholar 

  65. Erdelmeier, CAJ, Klessing K, Renzl S, Hauer H (1999) New hyperforin analogues from Hypericum perforatum and a stable dicyclohexylammonium salt of hyperforin. In: Luijendijk TJC, Verpoorte R (eds.) 2000 years of natural products research – past, present and future. Thieme Verlag, Stuttgart

    Google Scholar 

  66. Chatterjee SS, Erdelmeier C, Klessing K, Marme D, Schachtele C (2002) Stable hyperforin salts, method for producing same and their use in the treatment of Alzheimer’s disease. United States Patent 6, 444, 662 B1 2002

    Google Scholar 

  67. Gaid M, Haas P, Beuerle T, Scholl S, Beerhues L (2016) Hyperforin production in Hypericum perforatum root cultures. J Biotechnol 222:47–55

    Article  CAS  PubMed  Google Scholar 

  68. Verotta L, Appendino G, Belloro E, Jakupovic J, Bombardelli E (1999) Furohyperforin, a prenylated phloroglucinol from St. John’s Wort (Hypericum perforatum). J Nat Prod 62:770–772

    Article  CAS  PubMed  Google Scholar 

  69. Wolfender JL, Verotta L, Belvisi L, Fuzzati N, Hostettmann K (2003) Structural investigations of isomeric oxidised forms of hyperforin by HPLC-NMR and HPLC-MSn. Phytochem Anal 14:290–297

    Article  CAS  PubMed  Google Scholar 

  70. Kirakosyan A, Hayashi H, Inoue K, Charchoglyan A, Vardapetyan H (2000) Stimulation of the production of hypericins by mannan in Hypericum perforatum shoot cultures. Phytochemistry 53:345–348

    Article  CAS  PubMed  Google Scholar 

  71. Sirvent T, Gibson D (2002) Induction of hypericins and hyperforin in Hypericum perforatum L. in response to biotic and chemical elicitors. Physiol Mol Plant Pathol 60:311–320

    Article  CAS  Google Scholar 

  72. Kornfeld A, Kaufman RB, CR L, Gibson DM, Bolling SF, Warber SL, Chang SC, Kirakosyan A (2007) The production of hypericins in two selected Hypericum perforatum shoot cultures is related to differences in black gland structure. Plant Physiol Biochem 45:24–32

    Article  CAS  PubMed  Google Scholar 

  73. Tocci N, D’ Auria FD, Simonetti G, Panella S, Palamara AT, Debrassi A, Rodrigues CA, Filho VC, Sciubba F, Pasqua G (2013) Bioassay-guided fractionation of extracts from Hypericum perforatum in vitro roots treated with carboxymethylchitosans and determination of antifungal activity against human fungal pathogens. Plant Physiol Biochem 70:342–347

    Article  CAS  PubMed  Google Scholar 

  74. Tocci N, Simonetti G, D’Auria FD, Panella S, Palamara AT, Ferrari F, Pasqua G (2013) Chemical composition and antifungal activity of Hypericum perforatum subsp angustifolium roots from wild plants and plants grown under controlled conditions. Plant Biosyst 147:557–562

    Article  Google Scholar 

  75. Valletta A, De Angelis G, Badiali C, Brasili E, Miccheli A, Di Cocco ME, Pasqua G (2016) Acetic acid acts as an elicitor exerting a chitosan-like effect on xanthone biosynthesis in Hypericum perforatum L. root cultures. Plant Cell Rep 35:1009–1020

    Article  CAS  PubMed  Google Scholar 

  76. Wu SQ, XK Y, Lian ML, Park SY, Piao XC (2014) Several factors affecting hypericin production of Hypericum perforatum during adventitious root culture in airlift bioreactors. Acta Physiol Plant 36:975–981

    Article  CAS  Google Scholar 

  77. Cui XH, Murthy HN, Paek KY (2014) Pilot-scale culture of Hypericum perforatum L. adventitious roots in airlift bioreactors for the production of bioactive compounds. Appl Biochem Biotechnol 174:784–792

    Article  CAS  PubMed  Google Scholar 

  78. Conceição LFR, Ferreres F, Tavares RM, Dias ACP (2006) Induction of phenolic compounds in Hypericum perforatum L. cells by Colletotrichum gloeosporioides elicitation. Phytochemistry 67:149–155

    Article  PubMed  CAS  Google Scholar 

  79. Zobayed SMA, Saxena PK (2003) In vitro-grown roots: a superior explant for prolific shoot regeneration of St. John’s wort (Hypericum perforatum L. cv ´New Stem’) in a temporary immersion bioreactor. Plant Sci 165:463–470

    Article  CAS  Google Scholar 

  80. Goel MK, Kukreja AK, Bisht NS (2008) In vitro manipulations in St. John’s wort (Hypericum perforatum L.) for incessant and scale up micropropagation using adventitious roots in liquid medium and assessment of clonal fidelity using RAPD analysis. Plant Cell Tiss Organ Cult 96:1–9

    Article  Google Scholar 

  81. Charchoglyan A, Abrahamyan A, Fujii I, Boubakir Z, Gulder TAM, Kutchan TM, Vardapetyan H, Bringmann G, Ebizuka Y, Beerhues L (2007) Differential accumulation of hyperforin and secohyperforin in Hypericum perforatum tissue cultures. Phytochemistry 68:2670–2677

    Article  CAS  PubMed  Google Scholar 

  82. Karppinen K, Hokkanen J, Tolonen A, Mattila S, Hohtola A (2007) Biosynthesis of hyperforin and adhyperforin from amino acid precursors in shoot cultures of Hypericum perforatum. Phytochemistry 68:1038–1045

    Article  CAS  PubMed  Google Scholar 

  83. Steingroewer J, Bley T, Georgiev V, Ivanov I, Lenk F, Marchev A, Pavlov (2013) Bioprocessing of differentiated plant in vitro systems. Eng Life Sci 13:26–38

    Article  CAS  Google Scholar 

  84. Eibl R, Eibl D (2008) Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev 7:593–598

    Article  CAS  Google Scholar 

  85. Tocci N, Simonetti G, D’Auria FD, Panella S, Palamara AT, Valletta A, Pasqua G (2011) Root cultures of Hypericum perforatum subsp. angustifolium elicited with chitosan and production of xanthone-rich extracts with antifungal activity. Appl Microbiol Biotechnol 91:977–987

    Article  CAS  PubMed  Google Scholar 

  86. Gaid MM, Sircar D, Müller A, Beuerle T, Liu B, Ernst L, Hänsch R, Beerhues L (2012) Cinnamate:CoA ligase initiates the biosynthesis of a benzoate-derived xanthone phytoalexin in Hypericum calycinum cell cultures. Plant Physiol 160:1267–1280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Klingauf P, Beuerle T, Mellenthin A, El-Moghazya SAM, Boubakira Z, Beerhues L (2005) Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures. Phytochemistry 66:139–145

    Article  CAS  PubMed  Google Scholar 

  88. Malik S, Mirjalili MH, Fett-Neto AG, Mazzafera P, Bonfill M (2013) Living between two worlds: two phase culture systems for producing plant secondary metabolites. Crit Rev Biotechnol 33:1–22

    Article  CAS  PubMed  Google Scholar 

  89. Urbanová M, Košuth J, Cellárová E (2006) Genetic and biochemical analysis of Hypericum perforatum L. plants regenerated after cryopreservation. Plant Cell Rep 25:140–147

    Article  PubMed  CAS  Google Scholar 

  90. Skyba M, Faltus M, Zámečník J, Čellárová E (2011) Thermal analysis of cryopreserved Hypericum perforatum L. shoot tips: cooling regime dependent dehydration and ice growth. Thermochim Acta 514:22–27

    Article  CAS  Google Scholar 

  91. Bruňáková K, Zámećník J, Urbanová M, Čellárová E (2011) Dehydration status of ABA-treated and cold-acclimated Hypericum perforatum L. shoot tips subjected to cryopreservation. Thermochim Acta 525:62–70

    Article  CAS  Google Scholar 

  92. Bruňáková K, Cellárová E (2016) Conservation strategies in the genus Hypericum via cryogenic treatment. Front Plant Sci 7:1–12

    Article  Google Scholar 

  93. Panis B, Lambardi M (2006) Status of cryopreservation technologies in plants (crops and forest trees). In: Ruane J, Sonnino A (eds) The role of biotechnology in exploring and protecting agricultural genetic resources. United Nations Food and Agriculture Organization (FAO), Rome

    Google Scholar 

  94. Beerhues L (2011) Biosynthesis of the active Hypericum perforatum constituents. In: Odabas MS, Cirak C (eds) Medicinal and aromatic plant science and biotechnology. Global Science Books, Isleworth

    Google Scholar 

  95. Franklin G, Oliveira M, Dias ACP (2007) Production of transgenic Hypericum perforatum plants via particle bombardment-mediated transformation of novel organogenic cell suspension cultures. Plant Sci 172:1193–1203

    Article  CAS  Google Scholar 

  96. Tusevski O, Gadzovska Simic S (2013) Phenolic acids and flavonoids in Hypericum perforatum L. hairy roots. Int J Pharm Bio Sci 4:737–748

    Google Scholar 

  97. Zubrická D, Mišianiková A, Henzelyová J, Valletta A, De Angelis G, D’Auria FD, Simonetti G, Pasqua G, Céllárova E (2015) Xanthones from roots, hairy roots and cell suspension cultures of selected Hypericum species and their antifungal activity against Candida albicans. Plant Cell Rep 34:1953–1962

    Article  PubMed  CAS  Google Scholar 

  98. Bertoli A, Giovannini A, Ruffoni B, Guardo AD, Spinelli G, Mazzetti M, Pistelli L (2008) Bioactive constituent production in St. John’s Wort in vitro hairy roots regenerated plant lines. J Agric Food Chem 56:5078–5082

    Article  CAS  PubMed  Google Scholar 

  99. Koperdáková J, Komarovská H, Košuth J, Giovannini A, Čellárová E (2009) Characterization of hairy root-phenotype in transgenic Hypericum perforatum L. clones. Acta Physiol Plant 31:351–358

    Article  CAS  Google Scholar 

  100. Hou W, Shakya P, Franklin G (2016) A perspective on Hypericum perforatum genetic transformation. Front Plant Sci 7:1–12 Article 879

    Article  Google Scholar 

  101. Hageneder F (2007) Yew: a history. The History Press, Stroud

    Google Scholar 

  102. Eichenberger C, Heiselmayer P (1995) Die Eibe (Taxus baccata) in Salzburg, Versuch einer Monographie, vol 7. WUV-Universitätsverlag, Wien

    Google Scholar 

  103. Caesar GJ (53 BC) The gallic wars

    Google Scholar 

  104. Tekol Y (2007) The medieval physician Avicenna used an herbal calcium channel blocker, Taxus baccata L. Phytother Res 21:701–702

    Article  PubMed  Google Scholar 

  105. Alam G (2004) Database on medical plants (Asia). CUTS Centre for International Trade, Economics and Environment, Calcutta

    Google Scholar 

  106. Küpeli E, Erdemoğlu N, Yeşilada E, Şener B (2003) Anti-inflammatory and antinociceptive activity of taxoids and lignans from the heartwood of Taxus baccata L. J Ethnopharmacol 89:265–270

    Article  PubMed  CAS  Google Scholar 

  107. Renneberg R (2007) Biotech history: yew trees, paclitaxel synthesis and fungi. Biotechnol J 2:1207–1209

    Article  CAS  PubMed  Google Scholar 

  108. Itokawa H (2003) Introduction. In: Itokawa H, Lee K-H (eds) Taxus – the genus Taxus. Taylor & Francis, London

    Google Scholar 

  109. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327

    Article  CAS  PubMed  Google Scholar 

  110. Kingston DGI (2000) Recent advances in the chemistry of taxol 1,2. J Nat Prod 63:726–734

    Article  CAS  PubMed  Google Scholar 

  111. Cragg GM, Boyd MR, Cardellina JH II, Grever MR, Schepartz S, Snader KM, Suffness M (1993) The search for new pharmaceutical crops: drug discovery and development at the national cancer institute. Wiley, New York

    Google Scholar 

  112. Nims E, Dubois CP, Roberts SC, Walker EL (2006) Expression profiling of genes involved in paclitaxel biosynthesis for targeted metabolic engineering. Met Eng 8:385–394

    Article  CAS  Google Scholar 

  113. Malik S, Cusidó RM, Mirjalili MH, Moyano E, Palazón J, Bonfill M (2011) Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem 46:23–34

    Article  CAS  Google Scholar 

  114. Smith RF, Cameron SI (2002) Domesticating ground hemlock (Taxus canadensis) for producing taxanes: a case study. In: Proceedings of 29th annual meeting of the plant growth regulation society of America, LaGrange, Halifax, 40–45

    Google Scholar 

  115. Holton RA, Somoza C, Kim HB, Liang F, Biediger RJ, Boatman PD, Shindo M, Smith CC, Kim S (1994) First total synthesis of taxol. 1. Functionalization of the B ring. J Am Chem Soc 116:1597–1598

    Article  CAS  Google Scholar 

  116. Wuts PGM (1998) Semisynthesis of taxol. Curr Opin Drug Discov Dev 1:329–337

    CAS  Google Scholar 

  117. Vongpaseuth K, Roberts SC (2007) Advancements in the understanding of paclitaxel metabolism in tissue culture. Curr Pharm Biotechnol 8:219–236

    Article  CAS  PubMed  Google Scholar 

  118. Mountford PG (2010) The Taxol® story – development of a green synthesis via plant cell fermentation. In: Dunn PJ, Wells AS, Williams MT (eds) Green chemistry in the pharmaceutical industry. Wiley, New York

    Google Scholar 

  119. Kieran PM, MacLoughlin PF, Malone DM (1997) Plant cell suspension cultures: some engineering considerations. J Biotechnol 59:39–52

    Article  CAS  PubMed  Google Scholar 

  120. Trejo-Tapia G, Hernández-Trujillo R, Trejo-Espino JL, Jiménez-Aparicio A, Rodríguez-Monroy M (2003) Analysis of morphological characteristics of Solanum chrysotrichum cell suspension cultures. World J Microb Biotchnol 19:929–932

    Article  Google Scholar 

  121. Jeffers P, Raposo S, Lima-Costa M-E, Connolly P, Glennon B, Kieran PM (2003) Focussed beam reflectance measurement (FBRM) monitoring of particle size and morphology in suspension cultures of Morinda citrifolia and Centaurea calcitrapa. Biotechnol Lett 25:2023–2028

    Article  CAS  PubMed  Google Scholar 

  122. Grimm LH, Kelly S, Völkerding II, Krull R, Hempel DC (2005) Influence of mechanical stress and surface interaction on the aggregation of Aspergillus niger conidia. Biotechnol Bioeng 92:879–888

    Article  CAS  PubMed  Google Scholar 

  123. Rudolph G, Lindner P, Bluma A, Joeris K, Martinez G, Hitzmann B, Scheper T (2010) Optical inline measurement procedures for counting and sizing cells in bioprocess technology. In: Rao G (ed) Optical sensor systems in biotechnology, vol 116. Springer, Berlin/Heidelberg, pp 125–142

    Google Scholar 

  124. Pearson AP, Glennon B, Kieran PM (2003) Comparison of morphological characteristics of Streptomyces natalensis by image analysis and focused beam reflectance measurement. Biotechnol Prog 19:1342–1347

    Article  CAS  PubMed  Google Scholar 

  125. Ley I (2000) Assessing resolution and sensitivity in a laser diffraction particle size analyser. Am Lab 32:33–38

    CAS  Google Scholar 

  126. Lin PJ, Scholz A, Krull R (2010) Effect of volumetric power input by aeration and agitation on pellet morphology and product formation of Aspergillus niger. Biochem Eng J 49:213–220

    Article  CAS  Google Scholar 

  127. Wucherpfennig T, Hestler T, Krull R (2011) Morphology engineering – osmolality and its effect on Aspergillus niger morphology and productivity. Microb Cell Factories:11–58

    Google Scholar 

  128. Rønnest N, Stocks S, Lantz A, Gernaey K (2012) Comparison of laser diffraction and image analysis for measurement of Streptomyces coelicolor cell clumps and pellets. Biotechnol Lett 34:1465–1473

    Article  PubMed  CAS  Google Scholar 

  129. Kongsawadworakul P, Chrestin H (2003) Laser Diffraction: a new tool for identification and studies of physiological effectors involved in aggregation-coagulation of the rubber particles from Hevea latex. Plant Cell Physiol 44:707–717

    Article  CAS  PubMed  Google Scholar 

  130. Krull R, Wucherpfennig T, Eslahpazir Esfandabadi M, Walisko R, Melzer G, Hempel DC, Kampen I, Kwade A, Wittmann C (2013) Characterization and control of fungal morphology for improved production performance in biotechnology. J Biotechnol 163:112–123

    Article  CAS  PubMed  Google Scholar 

  131. Meijer JJ, ten Hoopen HJG, Luyben KCAM, Libbenga KR (1993) Effects of hydrodynamic stress on cultured plant cells: a literature survey. Enzym Microb Technol 15:234–238

    Article  CAS  Google Scholar 

  132. Midler M, Finn RK (1966) A model system for evaluating shear in the design of stirred fermentors. Biotechnol Bioeng 8:71–84

    Article  Google Scholar 

  133. Mandels M (1972) The culture of plant cells. Adv Biochem Eng 2:201–215

    Article  CAS  Google Scholar 

  134. Dunlop EH, Namdev PK, Rosenberg MZ (1994) Effect of fluid shear forces on plant cell suspensions. Chem Eng Sci 49:2263–2276

    Article  CAS  Google Scholar 

  135. Joshi JB, Elias CB, Patole MS (1996) Role of hydrodynamic shear in the cultivation of animal, plant and microbial cells. Chem Eng J/Biochem Eng J 62:121–141

    Article  CAS  Google Scholar 

  136. Papoutsakis ET (1991) Fluid-mechanical damage of animal cells in bioreactors. Trends Biotechnol 9:427–437

    Article  CAS  PubMed  Google Scholar 

  137. Scragg AH, Allan EJ, Leckie F (1988) Effect of shear on the viability of plant cell suspensions. Enzym Microb Technol 10:361–367

    Article  Google Scholar 

  138. Takeda T, Tamura M, Ohtaki M, Matsuoka H (2003) Gene expression in cultured strawberry cells subjected to hydrodynamic stress. Biochem Eng J 15:211–215

    Article  CAS  Google Scholar 

  139. Tanaka H (1981) Technological problems in cultivation of plant cells at high density. Biotechnol Bioeng 23:1203–1218

    Article  Google Scholar 

  140. Tanaka H, Semba H, Jitsufuchi T, Harada H (1988) The effect of physical stress on plant cells in suspension cultures. Biotechnol Lett 10:485–490

    Article  Google Scholar 

  141. Hooker BS, Lee JM, An G (1989) Response of plant tissue culture to a high shear environment. Enzym Microb Technol 11:484–490

    Article  CAS  Google Scholar 

  142. Leckie F, Scraggs AH, Cliffe KR (1991) Effect of impeller design and speed on the large-scale cultivation of suspension cultures of Catharanthus roseus. Enzym Microb Technol 13:801–810

    Article  CAS  Google Scholar 

  143. Zhong C, Yuan YJ (2009) Responses of Taxus cuspidata to hydrodynamics in bubble column bioreactors with different sparging nozzle sizes. Biochem Eng J 45:100–106

    Article  CAS  Google Scholar 

  144. Zhao D, Xing J, Li M, Lu D, Zhao Q (2001) Optimization of growth and jaceosidin production in callus and cell suspension cultures of Saussurea medusa. Plant Cell Tiss Org 67:227–234

    Article  CAS  Google Scholar 

  145. Märkl H, Bronnenmeier R, Wittek B (1987) Hydrodynamische Belastbarkeit von Mikroorganismen. Chem Ing Tech 59(12):907–917

    Article  Google Scholar 

  146. Bruňáková K, Babincová Z, Čellárová E (2004) Selection of callus cultures of Taxus baccata L. as a potential source of paclitaxel production. Eng Life Sci 4(5):465–469

    Article  CAS  Google Scholar 

  147. Bruňáková K, Babincová Z, Čellárová E (2005) Production of taxanes in callus and suspension cultures of Taxus baccata L. In: Hvoslef-Eide A, Preil W (eds) Liquid culture systems for in vitro plant propagation. Springer, Netherlands

    Google Scholar 

  148. Wickremesinhe ERM, Arteea RN (1993) Taxus callus cultures: initiation, growth optimization, characterization and taxol production. Plant Cell Tiss Org 35:181–193

    Article  CAS  Google Scholar 

  149. Wucherpfennig T, Schulz A, Pimentel A, Corkidi G, Sieblitz D, Pump M, Gorr G, Schütte K, Wittmann C, Krull R (2014) Viability characterization of Taxus chinensis plant cell suspension cultures by rapid colorimetric- and image analysis-based techniques. Bioproc Biosyst Eng 37:1799–1808

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge financial support from the Lower Saxony Ministry for Science and Culture in the joint research project Novel synthesis and formulation methods for poorly soluble drugs and sensitive biopharmaceuticals (SynFoBiA) within the Center for Pharmaceutical Process Engineering (PVZ) at the Technische Universität Braunschweig, Germany.

Author information

Authors and Affiliations

  1. Institute of Biochemical Engineering, Technische Universität Braunschweig, Rebenring 56, 38106, Braunschweig, Germany

    Thomas Wucherpfennig

  2. Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Braunschweig, Germany

    Mariam Gaid, Stephan Scholl, Ludger Beerhues & Rainer Krull

  3. Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Braunschweig, Germany

    Mariam Gaid, Stephan Scholl, Ludger Beerhues & Rainer Krull

Authors
  1. Mariam Gaid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Wucherpfennig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephan Scholl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ludger Beerhues
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rainer Krull
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rainer Krull .

Editor information

Editors and Affiliations

  1. University of Food Technologies, Plovdiv, Bulgaria

    Atanas Pavlov

  2. Bioprocess Engineering, Institute of Food Technology and Bioprocess Engineering, TU Dresden, Dresden, Germany

    Thomas Bley

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Gaid, M., Wucherpfennig, T., Scholl, S., Beerhues, L., Krull, R. (2018). Challenges for the Cultivation of Plant Cells on the Example of Hypericum perforatum and Taxus chinensis. In: Pavlov, A., Bley, T. (eds) Bioprocessing of Plant In Vitro Systems. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-54600-1_13

Download citation

Publish with us

Policies and ethics

Search

Navigation