Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering

Katja Jouhikainen, Laura Lindgren, Tuula Jokelainen, Raimo Hiltunen, Teemu Teeri, Kirsi-Marja Oksman-Caldentey

Research output: Contribution to journalArticleScientificpeer-review

130 Citations (Scopus)

Abstract

In order to test the possibility of enhancing the production of pharmaceutically valuable scopolamine in transgenic cultures, the 35S-h6h transgene that codes for the enzyme hyoscyamine-6β-hydroxylase (EC 1.14.11.11) was introduced into Hyoscyamus muticus L. strain Cairo (Egyptian henbane). This plant was chosen for its capability to produce very high amounts of tropane alkaloids (up to 6% of the dry weight in the leaves of mature plant). To our knowledge, this is the first time such a large population of transgenic cultures has been studied at the morphological, chemical and genetic levels. A great variation was observed in the tropane alkaloid production among the 43 positive transformants. The best clone (KB7) produced 17 mg/l scopolamine, which is over 100 times more than the control clones. However, conversion of hyoscyamine to scopolamine was still incomplete. The expression of h6h was found to be proportional to the scopolamine production, and was the main reason behind the variation in the scopolamine/hyoscyamine ratio in the hairy-root clones. These results indicate that H. muticus strain Cairo has a potential for even more enhanced scopolamine production with more efficient gene-expression systems.
Original languageEnglish
Pages (from-to)545-551
Number of pages7
JournalPlanta
Volume208
Issue number4
DOIs
Publication statusPublished - 1999
MoE publication typeA1 Journal article-refereed

Fingerprint

Hyoscyamus
Hyoscyamus muticus
scopolamine
Genetic Engineering
Scopolamine Hydrobromide
genetic engineering
Hyoscyamine
atropine
Tropanes
tropane alkaloids
Clone Cells
hyoscyamine (6S)-dioxygenase
clones
Alkaloids
genetically modified organisms
Plant Leaves
Mixed Function Oxygenases
mature plants
Transgenes
transgenes

Keywords

  • Genetic engineering
  • Hairy root
  • Hyoscyamus muticus
  • Scopolamine
  • Tropane alkaloids

Cite this

Jouhikainen, Katja ; Lindgren, Laura ; Jokelainen, Tuula ; Hiltunen, Raimo ; Teeri, Teemu ; Oksman-Caldentey, Kirsi-Marja. / Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. In: Planta. 1999 ; Vol. 208, No. 4. pp. 545-551.
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Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. / Jouhikainen, Katja; Lindgren, Laura; Jokelainen, Tuula; Hiltunen, Raimo; Teeri, Teemu; Oksman-Caldentey, Kirsi-Marja.

In: Planta, Vol. 208, No. 4, 1999, p. 545-551.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering

AU - Jouhikainen, Katja

AU - Lindgren, Laura

AU - Jokelainen, Tuula

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AU - Teeri, Teemu

AU - Oksman-Caldentey, Kirsi-Marja

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N2 - In order to test the possibility of enhancing the production of pharmaceutically valuable scopolamine in transgenic cultures, the 35S-h6h transgene that codes for the enzyme hyoscyamine-6β-hydroxylase (EC 1.14.11.11) was introduced into Hyoscyamus muticus L. strain Cairo (Egyptian henbane). This plant was chosen for its capability to produce very high amounts of tropane alkaloids (up to 6% of the dry weight in the leaves of mature plant). To our knowledge, this is the first time such a large population of transgenic cultures has been studied at the morphological, chemical and genetic levels. A great variation was observed in the tropane alkaloid production among the 43 positive transformants. The best clone (KB7) produced 17 mg/l scopolamine, which is over 100 times more than the control clones. However, conversion of hyoscyamine to scopolamine was still incomplete. The expression of h6h was found to be proportional to the scopolamine production, and was the main reason behind the variation in the scopolamine/hyoscyamine ratio in the hairy-root clones. These results indicate that H. muticus strain Cairo has a potential for even more enhanced scopolamine production with more efficient gene-expression systems.

AB - In order to test the possibility of enhancing the production of pharmaceutically valuable scopolamine in transgenic cultures, the 35S-h6h transgene that codes for the enzyme hyoscyamine-6β-hydroxylase (EC 1.14.11.11) was introduced into Hyoscyamus muticus L. strain Cairo (Egyptian henbane). This plant was chosen for its capability to produce very high amounts of tropane alkaloids (up to 6% of the dry weight in the leaves of mature plant). To our knowledge, this is the first time such a large population of transgenic cultures has been studied at the morphological, chemical and genetic levels. A great variation was observed in the tropane alkaloid production among the 43 positive transformants. The best clone (KB7) produced 17 mg/l scopolamine, which is over 100 times more than the control clones. However, conversion of hyoscyamine to scopolamine was still incomplete. The expression of h6h was found to be proportional to the scopolamine production, and was the main reason behind the variation in the scopolamine/hyoscyamine ratio in the hairy-root clones. These results indicate that H. muticus strain Cairo has a potential for even more enhanced scopolamine production with more efficient gene-expression systems.

KW - Genetic engineering

KW - Hairy root

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