Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell cultures

Elisabeth Moyano, Javier Palazon, Mercedes Bonfill, Lidia Osuna, Rosa M. Cusido, Kirsi-Marja Oksman-Caldentey, M. Teresa Pinol

Research output: Contribution to journalArticleScientificpeer-review

25 Citations (Scopus)

Abstract

Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into its epoxide scopolamine, a compound with a higher added value in the pharmaceutical market than hyoscyamine. We report the establishment of tobacco cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21 plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of scopolamine produced was quantified by HPLC. The transgenic cell suspension cultures showed a considerable capacity for the bioconversion of hyoscyamine into scopolamine, and released it to the culture medium. Although the scale-up from shake-flask to bioreactor culture usually results in reduced productivities, our transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode significantly increased the scopolamine accumulation.
Original languageEnglish
Pages (from-to)521-524
JournalJournal of Plant Physiology
Volume164
Issue number4
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

Fingerprint

Hyoscyamine
scopolamine
Scopolamine Hydrobromide
atropine
Biotransformation
biotransformation
Tobacco
cell culture
tobacco
Cell Culture Techniques
genetically modified organisms
hyoscyamine (6S)-dioxygenase
Hyoscyamus
Agrobacterium
Hyoscyamus muticus
Epoxy Compounds
Bioreactors
turbines
Rhizobium rhizogenes
Culture Media

Keywords

  • Biotransformation
  • Hyoscyamine-6beta-hydroxylase
  • Hyoscyamine
  • Scopolamine
  • Tobacco cell cultures

Cite this

Moyano, Elisabeth ; Palazon, Javier ; Bonfill, Mercedes ; Osuna, Lidia ; Cusido, Rosa M. ; Oksman-Caldentey, Kirsi-Marja ; Pinol, M. Teresa. / Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell cultures. In: Journal of Plant Physiology. 2007 ; Vol. 164, No. 4. pp. 521-524.
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abstract = "Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into its epoxide scopolamine, a compound with a higher added value in the pharmaceutical market than hyoscyamine. We report the establishment of tobacco cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21 plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of scopolamine produced was quantified by HPLC. The transgenic cell suspension cultures showed a considerable capacity for the bioconversion of hyoscyamine into scopolamine, and released it to the culture medium. Although the scale-up from shake-flask to bioreactor culture usually results in reduced productivities, our transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode significantly increased the scopolamine accumulation.",
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Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell cultures. / Moyano, Elisabeth; Palazon, Javier; Bonfill, Mercedes; Osuna, Lidia; Cusido, Rosa M.; Oksman-Caldentey, Kirsi-Marja; Pinol, M. Teresa.

In: Journal of Plant Physiology, Vol. 164, No. 4, 2007, p. 521-524.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell cultures

AU - Moyano, Elisabeth

AU - Palazon, Javier

AU - Bonfill, Mercedes

AU - Osuna, Lidia

AU - Cusido, Rosa M.

AU - Oksman-Caldentey, Kirsi-Marja

AU - Pinol, M. Teresa

PY - 2007

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N2 - Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into its epoxide scopolamine, a compound with a higher added value in the pharmaceutical market than hyoscyamine. We report the establishment of tobacco cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21 plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of scopolamine produced was quantified by HPLC. The transgenic cell suspension cultures showed a considerable capacity for the bioconversion of hyoscyamine into scopolamine, and released it to the culture medium. Although the scale-up from shake-flask to bioreactor culture usually results in reduced productivities, our transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode significantly increased the scopolamine accumulation.

AB - Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into its epoxide scopolamine, a compound with a higher added value in the pharmaceutical market than hyoscyamine. We report the establishment of tobacco cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21 plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of scopolamine produced was quantified by HPLC. The transgenic cell suspension cultures showed a considerable capacity for the bioconversion of hyoscyamine into scopolamine, and released it to the culture medium. Although the scale-up from shake-flask to bioreactor culture usually results in reduced productivities, our transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode significantly increased the scopolamine accumulation.

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