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Metabolic Engineering of Medicinal Plants tov Tropane Alkaloid Production

Tropane alkaloid의 생합성과 분자육종

  • Yun, Dae-Jin (Division of Applied Life Science (BK21 program), and Plant Molecular Biology and Biotechnology Research Center)
  • 윤대진 (경상대학교 대학원 응용생명과학부)
  • Published : 2002.09.01

Abstract

The tropane alkaloids hyoscyamine (its racemic form being atropine) and scopolamine are used medicinally as anticholinergic agents that act on the parasympathetic nerve system. Because they differ in their actions on the central nervous system, currently there is a 10-fold higher commercial demand for scopolamine, in the N-butylbromide form, than there is for hyoscyamine and atropine combined. Several solanaceous species have been used as the commercial sources of these alkaloids, but the scopolamine contents in these plants often are much lower than those of hyoscyamine. For this reason there has been long-standing interest in increasing the scopolamine contents of cultivated medicinal plants. Naturally occurring and artificial interspecific hybrids of Duboisia have high scopolamine contents and are cultivated as a commercial source of scopolamine in Australia and other countries. Anther culture combined with conventional interspecific hybridization also has been used to breed high scopolamine-containing plants in the genera Datura and Hyoscyamus, but without much success. The use of recombinant DNA technology for the manipulation of metabolic processes in cells promises to provide important contributions to basic science, agriculture, and medicine. In this review, I introduce on the enzymes and genes involved in tropane alkaloid biosynthesis and current progress in metabolic engineering approaches for tropane alkaloid, especially scopolamine, production.

Keywords

References

  1. Hashimoto T, Yamada, Y (1989) Biosynthesis of scopolamine from [7_^2H] 6f3-hydroxyhyoscyamine in Duboisia shoot cultures. Agric Bioi Chern 53:863-864 https://doi.org/10.1271/bbb1961.53.863
  2. Hashimoto T, Yamada Y (1994) Alkaloid biogenesis: Molecular aspects. Annu Rev Plant Physiol Plant Mol Biol 45:257-85 https://doi.org/10.1146/annurev.pp.45.060194.001353
  3. Hashimoto T, Yukimune Y, Yamada Y (1986) Tropane alkaloid production in Hyoscyamus root cultures. J Plant Physiol 124:6175
  4. Hashimoto T, Kohno J, Yamada Y (1989) 6{\beta}-hydroxyhyoscyamine epoxidase from cultured roots of Hyoscyamus niger. Phytochemistry 28: 1077-1082 https://doi.org/10.1016/0031-9422(89)80186-4
  5. Hashimoto T, Mitani A, Yamada Y (1990) Diamine oxidase from cultured roots of Hyoscyamus niger. Its function in tropane alkaloid biosynthesis. Plant PhysioI 93:216-221 https://doi.org/10.1104/pp.93.1.216
  6. Hashimoto T, Hayashi A, Amano Y, Kohno J, Iwanari S, Yamada Y (1991) Hyoscyamine 6f3-hydroxylase, an enzyme involved in tropane alkaloid biosynthesis, is localized at the pericyde of the root. J Biol Chem 266:4648-4653
  7. Hashimoto T, Nakajima K, Ongena G, Yamada Y (1992) Two tropinone reductases with distinct stereospecificities from cultured roots of Hyoscyamus niger. Plant Physiol. 100:836-845 https://doi.org/10.1104/pp.100.2.836
  8. Hashimoto T, Matsuda J., Yamada Y (1993) Two-step epoxidation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6f3-hydroxylase, FEBS Lett 329:35-39 https://doi.org/10.1016/0014-5793(93)80187-Y
  9. Hibi N, Fujita T, Hatano M, Hashimoto T, Yamada, Y (1992) Putrescine f'i-methytransferase in cultured roots of Hyoscyamus albus. Plant Physiol. 100:826-835 https://doi.org/10.1104/pp.100.2.826
  10. Hibi N, Higashiguchi S, Hashimito T, Yamada Y (1994) Gene expression in tobacco low-nicotine mutants. Plant cell 6:723-735 https://doi.org/10.1105/tpc.6.5.723
  11. Matsuda J, Okabe S, Hashimoto T, Yamada Y (1991) Molecular cloning of hyoscyamine 6${\beta}$-hydroxylase, a 2-oxoglutaratedependent dioxygenase, from cultured roots of Hyoscyamus niger. J Bioi Chern 266:9460-9464
  12. Nakajima K, Hashimoto T (1999) Two tropinone reductases, that catalyze opposite sterespecific reductions in tropane alkaloid biosynthesis, are localized in plant root with different cell-specific patterns. Plant cell Physiol 40: 1099-1107 https://doi.org/10.1093/oxfordjournals.pcp.a029494
  13. Nakajima, K, Hashimoto T, Yamada Y (1993) Two tropinone reductases with different stereospecificties are short-chain dehydrogenases evolved from a common ancestor. Proc Natl Mad Sci USA 90:9591-9595 https://doi.org/10.1073/pnas.90.20.9591
  14. Nakajima K, Hashimoto T, Yamada Y (1994) Opposite stereospecificity of two tropinone reductases is conferred by the substratebinding sites. J. Biol.Chem. 269:11695-11698
  15. Nakajima K, Yamada Y, Akama H, Nakatsu T, Kato H, Hashimoto T, Oda JI, Yamada Y (1998) Crystal structures of two tropinone reductases: Different reaction stereospecificities in the same protein fold. Proc Natl Acad Sci USA 95:4876-4881 https://doi.org/10.1073/pnas.95.9.4876
  16. Nakajima K, Kato H, Oda JI, Yamada Y, Hashimoto T (1999) Sitedirected mutagenesis of putative substrate-binding residues reveals a mechanism controling the different stereospecificities of two tropinone reductases.Proc Natl Acad Sci USA 274:16563-16568
  17. Shoji T, Nakajima K, Hashimoto T (2000) Ethylene suppresses jasmonate-induced gene expression in nicotine biosynthesis. Plant Cell Physiol 41:1072-1076 https://doi.org/10.1093/pcp/pcd027
  18. Suzuki KI, Yamada Y, Hashimoto T (1999) Expression of Atropa belladonna putrescine N-methytransferaes gene in root pericycle. Plant Cell Physiol 40:289-297 https://doi.org/10.1093/oxfordjournals.pcp.a029540
  19. Yamada Y, Hashimoto T (1989) Substrate specificity of hyoscyamine 6${\beta}$-hydroxylase from cultured root of Hyoscyamus niger. Proc Jpn Acad Sci Ser B 65: 156-159 https://doi.org/10.2183/pjab.65.156
  20. Yamada Y, Okabe Y, Hashimoto T (1990) Homogeneous hyoscyamine 6${\beta}$-hydroxylase from cultured root of Hyoscyamus niger. Proc Jpn Acad Sci Ser B 66:73-76 https://doi.org/10.2183/pjab.66.73
  21. Yun DJ, Hashimoto T, Yamada Y (1992) Metabolic engineering of medicinal plants: Transgenic Atropa belladonna with an improved alkaloid composition. Proc Natl Acad Sci USA 89: 11799-11803 https://doi.org/10.1073/pnas.89.24.11799
  22. Yun DJ, Hashimoto T, Yamada Y(1993) Transgenic tobacco plants with tow consecutive oxidation reactions catalyzed by hyoscyamine 6${\beta}$-hydroxylase. Biosci Biotech Biochem 57:502-503 https://doi.org/10.1271/bbb.57.502