Abstract
The application of cyclodextrins as precursor solubilizers in biotechnological processes, in which plant cells are involved, is new. In this paper the possibilities for cyclodextrin facilitated bioconversions by freely suspended and/or immobilized plant cells or plant enzymes are demonstrated. After complexation with β-cyclodextrin, the phenolic steroid 17β-estradiol could be ortho-hydroxylated into a catechol, mainly 4-hydroxyestradiol, by a phenoloxidase from in vitro grown cells of Mucuna pruriens. By complexation with β-cyclodextrin the solubility of the steroid increased from almost insoluble to 660 μM. In addition, by complexation with β-cyclodextrin, a solution of 3 mM coniferyl alcohol could be fed to cell cultures of Podophyllum hexandrum in order to enhance the accumulation of podophyllotoxin. Finally, the glucosylation of podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin and dimethyl-β-cyclodextrin were used to improve the solubility of podophyllotoxin. Dimethyl-β-cyclodextrin met our needs the best and the solubility of podophyllotoxin could be enhanced from 0.15 to 1.92 mM. Podophyllotoxin-β-d-glucoside was formed at a rate of 0.51 mmol l-1 suspension per day by the L. flavum cells growing in the presence of 1.35 mM podophyllotoxin, complexed with dimethyl-β-cyclodextrin.
Similar content being viewed by others
Abbreviations
- DW:
-
dry weight
- E2:
-
17β-estradiol
- FW:
-
fresh weight
- PCV:
-
packed cell volume
References
Berlin J, Wray V, Mollenschott C & Sasse F (1986) Formation of β-peltatin-A-methylether and coniferin by root cultures of Linum flavum. J. Nat. Prod. 49: 435–439
Berlin J, Bedorf N, Mollenschott C, Wray V, Sasse F & Höfle G (1988) On the podophyllotoxins of root cultures of Linum flavum. Planta Med. 54: 204–206
Duchêne D & Wouessidjewe D (1990a) Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, Part I. Pharm. Technol. 14 (6): 26–34
Duchêne D & Wouessidjewe D (1990b) Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, Part II. Pharm. Technol. 14 (8): 22–30
Hesselink PGM, Van Vliet S, De Vries H & Witholt B (1989) Optimization of Mycobacterium steroid side chain cleavage in the presence of cyclodextrins. Enzyme Microbiol. Technol. 11: 398–404
Higuchi T & Connors K (1965) Phase solubility techniques. Adv. Anal. Chem. Industr. 4: 117–212
Hirayama F & Uekama K (1987) Methods of investigating and preparing inclusion compounds. In: Duchêne D (Ed) Cyclodextrins and Their Industrial Uses (pp 131–172). Editions de Santé, Paris
Hösel W (1981) Glycosylation and glycosidases. In: Conn EE, Stumpf PK (Ed) The Biochemistry of Plants, Vol 7 (pp 725–753). Academic Press, New York
Jackson DE & Dewick PM (1984) Biosynthesis of Podophyllum lignans — II. Interconversions of aryltetralin lignans in Podophyllum hexandrum. Phytochemistry 23: 1037–1042
Le Bas G & Rysanek N (1987) Structural aspects of cyclodextrins. In: Duchêne D (Ed) Cyclodextrins and Their Industrial Uses (pp 105–130). Editions de Santé, Paris
Luckner M (1986) In: Secondary Metabolism in Microorganisms, Plants and Animals, 2nd edition. Springer-Verlag, Heidelberg/New York/Tokyo
Mayer AM (1987) Polyphenol oxidases in plants — recent progress. Phytochemistry 26: 11–20
Müller BW & Brauns U (1986) Hydroxypropyl-β-cyclodextrin derivatives: influence of average degree of substitution on complexing ability and surface activity. J. Pharm. Sci. 75 (6): 571–572
Pras N (1989) Biotechnological production of catechols: bioconversion spectrum and related kinetic aspects of entrapped cells of Mucuna pruriens L. Pharm. Weekbl. Sci. ed. 11: 30–31
Pras N (1992) Bioconversion of naturally occurring precursors and related synthetic compounds using plant cell cultures: a review. J. Biotechnol. 26: 29–62
Pras N, Wichers HJ, Bruins AP & Malingré ThM (1988) Bioconversion of para-substituted monophenolic compounds into corresponding catechols by alginate-entrapped cells of Mucuna pruriens. Plant Cell Tiss. Org. Cult. 13: 15–26
Pras N, Hesselink PGM, Guikema WM & Malingré ThM (1989) Further kinetic characterization of alginate-entrapped cells of Mucuna pruriens L. Biotechnol. Bioeng. 33: 1461–1468
Saenger W (1984) Structural aspects of cyclodextrins and their inclusion complexes. In: Atwood JL, Davies JED & MacNicol DD (Eds) Inclusion Compounds (pp 231–259). Academic Press, London
Sébille B (1987) Cyclodextrin derivatives. In: Duchêne D (Ed) Cyclodextrins and Their Industrial Uses (pp 353–392). Editions de Santé, Paris
Sicard PJ & Saniez MH (1987) Biosynthesis of cycloglucosyl-transferase and obtention of its enzymatic reaction products. In: Duchêne D (Ed) Cyclodextrins and Their Industrial Uses (pp 77–103). Editions de Santé, Paris
Szejtli J & Pagington J (1989) Solubility isotherms. Cyclodextrin News 3: 77–79
Uekama K, Narisawa S, Hirayama F & Otagiri M (1983) Improvement of dissolution and absorption characteristics of benzodiazepines by cyclodextrin complexation. Int. J. Pharm. 16: 327–338
Uekama K & Irie T (1987) Pharmaceutical applications of methylated cyclodextrin derivatives. In: Duchêne D (Ed) Cyclodextrins and Their Industrial Uses (pp 395–439). Editions de Santé, Paris
Van Uden W, Pras N, Visser JF & Malingré ThM (1989) Detection and identification of podophyllotoxin produced by cell cultures derived from Podophyllum hexandrum Royle. Plant Cell Rep. 8: 165–168
Van Uden W, Pras N, Vossebeld EM, Mol JNM & Malingré ThM (1990a) Production of 5-methoxypodophyllotoxin in cell suspension cultures of Linum flavum L. Plant Cell Tiss. Org. Cult. 20: 81–87
Van Uden W, Pras N & Malingré ThM (1990b) On the improvement of the podophyllotoxin production by phenylpropanoid precursor feeding to cell cultures of Podophyllum hexandrum Royle. Plant Cell Tiss. Org. Cult. 23: 217–224
Van Uden W, Pras N, Batterman S, Visser JF & Malingré ThM (1991a) The accumulation and isolation of coniferin from a high-producing cell suspension of Linum flavum L. Planta 183: 25–30
Van Uden W, Pras N, Homan B & Malingré ThM (1991b) Improvement of the production of 5-methoxypodophyllotoxin using a new selected root culture of Linum flavum L. Plant Cell Tiss. Org. Cult. 27: 115–121
Van Uden W, Homan B, Woerdenbag HJ, Pras N & Malingré ThM, Wichers HJ & Harkes M (1992) Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum. J. Nat. Prod. 55: 102–110
Van Uden W, Oeij H, Woerdenbag HJ & Pras N (1993) Glucosylation of cyclodextrin-complexed podophyllotoxin by cell cultures of Linum flavum L. Plant Cell Tiss. Org. Cult. (in press)
Wichers HJ, Harkes MP & Arroo RJ (1990) Occurrence of 5-methoxypodophyllotoxin in plants, cell cultures and regenerated plants of Linum flavum. Plant Cell Tiss. Org. Cult. 23: 93–100
Wichers HJ, Versluis-De Haan GG, Marsman JW & Harkes MP (1991) Podophyllotoxins in plants and cell cultures of Linum flavum. Phytochemistry 30: 3601–3604
Woerdenbag HJ, Pras N, Frijlink HW, Lerk CF & Malingré ThM (1990a) Cyclodextrin-facilitated bioconversion of 17β-estradiol by a phenoloxidase from Mucuna pruriens cell cultures. Phytochemistry 29: 1551–1554
Woerdenbag HJ, Van Uden W, Frijlink HW, Lerk CF, Pras N & Malingré ThM (1990b) Increased podophyllotoxin production in Podophyllum hexandrum cell suspension cultures after feeding coniferyl alcohol as a β-cyclodextrin complex. Plant Cell Rep. 9: 97–100
Yamamoto M, Yoshida A, Hirayama F & Uekama K (1989) Some physicochemical properties of branched β-cyclodextrins and their inclusion characteristics. Int. J. Pharm. 49: 163–171
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
van Uden, W., Woerdenbag, H.J. & Pras, N. Cyclodextrins as a useful tool for bioconversions in plant cell biotechnology. Plant Cell Tiss Organ Cult 38, 103–113 (1994). https://doi.org/10.1007/BF00033867
Issue Date:
DOI: https://doi.org/10.1007/BF00033867