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Biosynthesis of Alkaloids Using Plant Cell Cultures

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Part of the book series: Recent Advances in Phytochemistry ((RAPT,volume 23))

Abstract

With an estimated 7000 individual structures thus far isolated from plant material, alkaloids are the most diverse of all low molecular weight nitrogen containing compounds. The amount of nitrogen immobilized in these structures varies drastically but, for instance, in cell suspension cultures of Berberis stolonifera which produce up to 3 g of protoberberine alkaloids per liter of medium,1 15% of the nitrogen supplied in the medium can be found in alkaloids. Plants in general in their natural environment are nitrogen limited; therefore the sacrifice of valuable nitrogen fixed into alkaloids which generally have no apparent turnover but rather are dead end products is justified only by the fact that these metabolites serve important ecochemic functions for the differentiated plant.2 The extreme diversity of alkaloids and their use as pharmaceuticals3 and stimulatory agents (i.e., caffeine, nicotine) of considerable commercial value make this group of compounds an interesting subject for studying their formation within the living system. At this stage of development of plant biochemistry, the elucidation of biosynthetic pathways for secondary compounds has become possible.

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References

  1. HINZ, H., M.H. ZENK. 1981. Production of protoberberine alkaloids by cell suspension cultures of Berberis species. Naturwissenschaften 67: 620.

    Article  ADS  Google Scholar 

  2. HARBORNE, J.B. 1982. Introduction to Ecological Biochemistry. Academic Press, London, New York, 2nd Edition, 278 pp.

    Google Scholar 

  3. FARNSWORTH, N.R. 1984. The role of medicinal plants in drug development. In Natural Products and Drug Development. (P. Krogsgaard-Larsen, S.B. Christensen, H. Kofod, eds.), Munksgaard, Copenhagen, pp. 1–30.

    Google Scholar 

  4. EBEL, J., K. HAHLBROCK. 1982. Biosynthesis. In The Flavonoids, Advances in Research. (J.B. Harborne, T.J. Mabry, eds.), Chapman and Hall, London, New York, pp. 641–680.

    Google Scholar 

  5. STÖCKIGT, J. 1986. Enzymatic biosynthesis of indole alkaloids: ajmaline, sarpagine, vindoline. In New Trends in Natural Products Chemistry, 1986, Studies in Organic Chemistry. (Atta-ur-Rahman, P.W. Le Quesne, eds.), Elsevier Science Publishers B.V., Amsterdam, Vol. 26, pp. 497–511.

    Google Scholar 

  6. ZENK, M.H., M. RUEFFER, T.M. KUTCHAN, E. GALNEDER. 1988. Biotechnological approaches to the production of isoquinoline alkaloids. In Application of Plant Cell and Tissue Culture. Ciba Foundation Symposium No. 137, Wiley, Chichester, pp. 213–227.

    Google Scholar 

  7. CORDELL, G.A. 1981. Introduction to Alkaloids. John Wiley-Interscience, New York, pp. 330–517.

    Google Scholar 

  8. TANAHASHI, T., M.H. ZENK. 1985. Isoquinoline alkaloids from cell suspension cultures of Fumaria capreolata. Plant Cell Rep. 4: 96–99.

    Article  Google Scholar 

  9. ZENK, M.H. 1985. Enzymology of benzylisoquinoline alkaloid formation. In The Chemistry and Biology of Isoquinoline Alkaloids. (J.D. Phillipson, M.F. Roberts, M.H. Zenk, eds.), Springer-Verlag, Berlin, Heidelberg, New York, Tokyo, pp. 240–256.

    Google Scholar 

  10. ZENK, M.H., M. RUEFFER, M. AMANN, B. DEUS-NEUMANN, N. NAGAKURA. 1985. Benzylisoquinoline biosynthesis by cultivated plant cells and isolated enzymes. J. Nat. Prod. (Lloydia) 48: 725–738.

    Article  Google Scholar 

  11. RUEFFER, M., H. EL-SHAGI, N. NAGAKURA, M.H. ZENK. 1981. (S)-Norlaudanosoline synthase: The first enzyme in the benzylisoquinoline biosynthetic pathway. FEBS Lett. 129: 5–9.

    Article  Google Scholar 

  12. SCHUMACHER, H.M., M. RUEFFER, N. NAGAKURA, M.H. ZENK. 1983. Partial purification and properties of (S)-norlaudanosoline synthase from Eschscholtzia tenuifolia cell cultures. Planta Med. 48: 212–220.

    Article  Google Scholar 

  13. SPENSER, I.D. 1968. The biosynthesis of alkaloids and other nitrogenous secondary metabolites. In Comprehensive Biochemistry. (M. Florkin, E.H. Stotz, eds.), Elsevier, Amsterdam, Vol. 20, pp. 231–413.

    Google Scholar 

  14. HOLLAND, H., P. JEFFS, T.M. CAPPS, D.B. MACLEAN. 1979. The biosynthesis of protoberberine and related isoquinoline alkaloids. Can. J. Chem. 57: 1588–1597.

    Article  Google Scholar 

  15. CASSELS, B.K., E. BREITMAIER, M.H. ZENK. 1987. Bisbenzylisoquinoline alkaloids in Berberis cell cultures. Phytochemistry 26: 1005–1008.

    Article  Google Scholar 

  16. STADLER, R., T.M. KUTCHAN, S. LOEFFLER, N. NAGAKURA, B.K. CASSELS, M.H. ZENK. 1987. Revision of the early steps of reticuline biosynthesis. Tetrahedron Lett. 28: 1251–1254.

    Article  Google Scholar 

  17. GOPINATH, K.W., T.R. GOVINDACHARI, B.R. PAI, N. VISWANATHAN. 1959. Konstitution von Reticulin, einem neuen Alkaloid aus Annona reticulata Linn. Chem. Ber. 92: 776–779.

    Article  Google Scholar 

  18. STADLER, R., S. LOEFFLER, B.K. CASSELS, M.H. ZENK. 1988. Bisbenzylisoquinoline biosynthesis in Berberis stolonifera cell cultures. Phytochemistry 27: 2557–2565.

    Article  Google Scholar 

  19. LOEFFLER, S., R. STADLER, N. NAGAKURA, M.H. ZENK. 1987. Norcoclaurine as biosynthetic precursor of thebaine and morphine. J. Chem. Soc. Chem. Commun., 1160–1162.

    Google Scholar 

  20. WIECZOREK, U., N. NAGAKURA, C. SUND, S. JENDRZEJEWSKI, M.H. ZENK. 1986. Radioimmunoassay determination of six opium alkaloids and its application to plant screening. Phytochemistry 25: 2639–2646.

    Article  Google Scholar 

  21. STADLER, R., T.M. KUTCHAN, M.H. ZENK. 1988. (S)-Norcoclaurine is the central intermediate in benzylisoquinoline alkaloid biosynthesis. Phytochemistry, in press.

    Google Scholar 

  22. KOSHIYAMA, H., H. OHKUMA, H. KAWAGUCHI, H.-Y. HSU, Y.-P. CHEN. 1979. Isolation of 1-(p-hydroxybenzyl)-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline (demethylcoclaurine), an active alkaloid from Nelumbo nucifera. Chem. Pharm. Bull, 18: 2564–2568.

    Google Scholar 

  23. KOSUGE, T., M. YOKOTA. 1976. Studies on cardiac principle of aconite root. Chem. Pharm. Bull. 24: 176–178.

    Google Scholar 

  24. KOSUGE, T., M. YOKOTA, H. NUKAYA, Y. GOTOH, M. NAGASAWA. 1978. Studies on antitussive principles of Asiasari Radix. Chem. Pharm. Bull. 26: 2284–2285.

    Google Scholar 

  25. WAGNER, H., M. REITER, W. FERSTL. 1980. New drugs with cardiotonic activity. I. Chemistry and pharmacology of the cardiotonic active principle of Annona squamosa L. Planta Med. 40: 77–85.

    Article  Google Scholar 

  26. LeBOEUF, M., A. CAVÉ, A. TOUCHÉ, J. PROVOST, P. FORGACS. 1981. Isolement de L’Higénamine a Partir de L’Annona squamosa; Interet des Résines Adsorbantes Macromoléculaires en Chimie Végétale Extractive. J. Nat. Prod. (Lloydia) 44: 53–60.

    Article  Google Scholar 

  27. RUEFFER, M., M.H. ZENK. 1987. Distant precursors of benzylisoquinoline alkaloids and their enzymatic formation. Z. Naturforsch. 42c: 319–332.

    Google Scholar 

  28. CONNELLY, J.A., E.E. CONN. 1986. Tyrosine biosynthesis in Sorghum bicolor: Isolation and regulatory properties of arogenate dehydrogenase. Z. Naturforsch. 41c: 69–78.

    Google Scholar 

  29. BATTERSBY, A.R., R. BINKS. 1960. Biosynthesis of morphine: Formation of morphine from norlauda-nosoline. Proc. Chem. Soc., 360–361.

    Google Scholar 

  30. BATERSBY, A.R., R. BINKS, R.J. FRANCIS, D.J. MACCALDIN, H. RAMUZ. 1964. Alkaloid biosynthesis. Part IV. 1-Benzylisoquinolines as precursors of thebaine, codeine and morphine. J. Chem. Soc., 3600–3610.

    Google Scholar 

  31. BROCHMANN-HANSSEN, E., C.H. CHEN, R. CHEN, H.C. CHIAN, A.Y. LEUNG, K. McMURTREY. 1975. The biosynthesis of 1-benzylisoquinolines in Papaver somniferum. Preferred and secondary pathways, stereochemical aspects. J. Chem. Soc. Perkin Trans I, 1531–1537.

    Article  Google Scholar 

  32. LOEFFLER, S. 1988. Norcoclaurin: das zentrale Zwischenprodukt in der Biosynthese der Benzylisochinolinalkaloide. Dissertation der Fakultät für Chemie und Pharmazie der Universität München.

    Google Scholar 

  33. JOHNS, S.R., J.A. LAMBERTON, A.A. SIOUMIS. 1967a. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids from Alseodaphne archboldiana (Allen) Kostermans. Aust. J. Chem. 20: 1729–1735.

    Article  Google Scholar 

  34. FRENZEL, T., N. NAGAKURA, N.H. ZENK. 1989. S-Adenosyl-L-methionine: 6-0-methyllaudanosoline 4’-0-methyltransferase a regio and stereospecific enzyme of the (S)-reticuline pathway. Phytochemistry, in press.

    Google Scholar 

  35. WINTERSTEIN, E., G. TRIER. 1910. Die Alkaloide. Gebrüder Bornträger, Berlin, p. 307.

    Google Scholar 

  36. ROBINSON, R. 1917. A theory of the mechanism of the phytochemical synthesis of certain alkaloids. J. Chem. Soc. 111: 876–899.

    Google Scholar 

  37. ROBINSON, R. 1955. The Structural Relations of Natural Products. Clarendon Press, Oxford, 150 pp.

    Google Scholar 

  38. FUJITA, Y., M. TABATA. 1987. Secondary metabolites from plant cells — pharmaceutical applications and progress in commercial production. In Plant Tissue and Cell Culture. (C.E. Green et al., eds.), Alan R. Liss, New York, pp. 169–186.

    Google Scholar 

  39. AMANN, M., N. NAGAKURA, M.H. ZENK. 1984. (S)-Tetrahydroprotoberberin oxidase the final enzyme in protoberberine biosynthesis. Tetrahedron Lett. 25: 953–954.

    Article  Google Scholar 

  40. AMANN, M., N. NAGAKURA, N.H. ZENK. 1988. Purification and properties of (S)-tetrahydro-protoberberine oxidase from suspension-cultured cells of Berberis wilsoniae. Eur. J. Biochem. 175: 17–25.

    Article  Google Scholar 

  41. YAMADA, Y., OKADA, N. 1985. Biotransformation of tetrahydroberberine to berberine by enzymes prepared from cultured Coptis japonica cells. Phytochemistry 24: 63–65.

    Article  Google Scholar 

  42. OKADA, N., A. SHINMYO, H. OKADA, Y. YAMADA. 1988. Purification and characterization of (S)-tetrahydroberberine oxidase from cultured Coptis japonica cells. Phytochemistry 27: 979–982.

    Article  Google Scholar 

  43. GALNEDER, E., M. RUEFFER, G. WANNER, M. TABATA, M.H. ZENK. 1988. Alternative final steps in berberine biosynthesis in Coptis japonica cell cultures. Plant Cell Rep. 7: 1–4.

    Article  Google Scholar 

  44. RUEFFER, M., M.H. ZENK. 1985. Berberine synthase, the methylenedioxy group forming enzyme in berberine synthesis. Tetrahedron Lett. 26: 201–202.

    Article  Google Scholar 

  45. AMANN, M., G. WANNER, M.H. ZENK. 1986. Intracellular compartmentation of two enzymes of berberine biosynthesis in plant cell cultures. Planta 167: 310–320.

    Article  Google Scholar 

  46. BÖHM, H., E. RINK. 1975. Zue Rolle eines Reticulinumwandelnden Enzyms (Berberin-Brücken-Enzym) im pflanzlichen Benzylisochinolin-Stoffwechsel. Biochem. Physiol. Pflanz. 168: 69–77.

    Google Scholar 

  47. RINK, E., H. BÖHM. 1975. Conversion of reticuline into scoulerine by a cell-free preparation from Macleaya microcarpa cell suspension cultures. FEBS Lett. 49: 396–399.

    Article  Google Scholar 

  48. STEFFENS, P., N. NAGAKURA, M.H. ZENK. 1985. Purification and characterization of the berberine bridge enzyme from Berberis beaniana cell cultures. Phytochemistry 24: 2577–2583.

    Article  Google Scholar 

  49. TAKAO, N., M. KAMIGAUCHI, M. OKADA. 1983. Biosynthesis of benzo[c]phenanthridine alkaloids sanguinarine, chelirubine and macarpine. Helv. Chim. Acta 66: 473–484.

    Article  Google Scholar 

  50. RUEFFER, M., M.H. ZENK. 1986. S-Adenosyl-L-methionine: (S)-7,8,13,14-tetrahydroberberine cis-N-methyltransferase, a branch point enzyme in the biosynthesis of benzophenanthridine and protopine alkaloids. Tetrahedron Lett. 27: 5603–5604.

    Article  Google Scholar 

  51. RÖNSCH, H. 1986. Rhoeadine alkaloids. In The Alkaloids. (A. Brossi, ed.), Academic Press, New York, London, Vol. 28, pp. 1–93.

    Google Scholar 

  52. MADYASTHA, K.M., T.D. MEEHAN, C.J. COSCIA. 1976. Characterization of a cytochrome P-450 dependent monoterpene hydroxylase from the higher plant Vinca rosea. Biochemistry 15: 1097–1102.

    Article  Google Scholar 

  53. RIVIERE, J.-L., F. CABANNE. 1987. Animal and plant cytochrome P-450 systems. Biochimie 69: 743–752.

    Article  Google Scholar 

  54. RUEFFER, M., M.H. ZENK. 1987. Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans. Tetrahedron Lett. 28: 5307–5310.

    Article  Google Scholar 

  55. JENDRZEJEWSKI, S. 1989. Detection of reticuline degradation in Berberis suspension cultures by 13C in vivo NMR. Phytochemistry, in press.

    Google Scholar 

  56. NOVER, L. 1984. Heat-shock Response of Eucaryotic Cells. Springer-Verlag, Berlin, 82 pp.

    Google Scholar 

  57. MENACHERY, M.D., G.L. LAVANIER, M.L. WETHERLY, H. GUINAUDEAU, M. SHAMMA. 1986. Simple isoquinoline alkaloids. J. Nat. Prod. (Lloydia) 49: 745–778.

    Article  Google Scholar 

  58. IWASA, K., M. KAMIGAUCHI, N. TAKAO. 1987. Biotransformation of phthalideisoquinoline alkaloids by Corydalis tissue culture. Arch. Pharm. (Weinheim) 320: 693–697.

    Article  Google Scholar 

  59. LUNDSTRÖM, J. 1985. The occurrence of simple isoquinolines in plants. Op. cit. Reference 9, pp. 47–61.

    Google Scholar 

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Zenk, M.H. (1989). Biosynthesis of Alkaloids Using Plant Cell Cultures. In: Poulton, J.E., Romeo, J.T., Conn, E.E. (eds) Plant Nitrogen Metabolism. Recent Advances in Phytochemistry, vol 23. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0835-5_12

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  • DOI: https://doi.org/10.1007/978-1-4613-0835-5_12

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