Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over-expressing the alpha or the alpha and beta subunits of anthranilate synthase

Christie A.M. Peebles, Seung Beom Hong, Sue Gibson, Jacqueline V. Shanks, Ka Yiu San

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Among the pharmacologically important terpenoid indole alkaloids produced by Catharanthus roseus are the anti-cancer drugs vinblastine and vincristine. These two drugs are produced in small yields within the plant, which makes them expensive to produce commercially. Metabolic engineering has focused on increasing flux through this pathway by various means such as elicitation, precursor feeding, and introduction of genes encoding specific metabolic enzymes into the plant. Recently in our lab, a feedback-resistant anthranilate synthase α subunit was over-expressed in C. roseus hairy roots under the control of a glucocorticoid inducible promoter system. Upon induction we observed a large increase in the indole precursors, tryptophan, and tryptamine. The current work explores the effects of overexpressing the anthranilate synthase α or α and β subunits in combination with feeding with the terpenoid precursors 1-deoxy-D-xylulose, loganin, and secologanin. In feeding 1-deoxy-D-xylulose to the hairy root line expressing the anthranilate synthase α subunit, we observed an increase of 125% in hörhammericine levels in the induced samples, while loganin feeding increased catharanthine by 45% in the induced samples. Loganin feeding to the hairy root line expressing anthranilate synthase α and β subunits increases catharanthine by 26%, ajmalicine by 84%, lochnericine by 119%, and tabersonine by 225% in the induced samples. These results suggest that the terpenoid precursors to the terpenoid indole alkaloids are important factors in terpenoid indole alkaloid production.

Original languageEnglish (US)
Pages (from-to)534-540
Number of pages7
JournalBiotechnology and Bioengineering
Volume93
Issue number3
DOIs
StatePublished - Feb 20 2006

Fingerprint

Anthranilate Synthase
Catharanthus
Secologanin Tryptamine Alkaloids
Terpenes
Alkaloids
Xylulose
Metabolic Engineering
Vinblastine
Metabolic engineering
Vincristine
Gene encoding
Tryptophan
Pharmaceutical Preparations
Glucocorticoids
Enzymes
Fluxes
Feedback
Genes
loganin
Neoplasms

Keywords

  • Anthranilate synthase
  • Catharanthus roseus
  • Hairy roots
  • Precursor feeding
  • Terpenoid indole alkaloids

Cite this

Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over-expressing the alpha or the alpha and beta subunits of anthranilate synthase. / Peebles, Christie A.M.; Hong, Seung Beom; Gibson, Sue; Shanks, Jacqueline V.; San, Ka Yiu.

In: Biotechnology and Bioengineering, Vol. 93, No. 3, 20.02.2006, p. 534-540.

Research output: Contribution to journalArticle

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