Phytochemistry Reviews

, Volume 6, Issue 2–3, pp 435–457 | Cite as

Manipulating indole alkaloid production by Catharanthus roseus cell cultures in bioreactors: from biochemical processing to metabolic engineering

Article

Abstract

Catharanthus roseus plants produce many pharmaceutically important indole alkaloids, of which the bisindole alkaloids vinblastine and vincristine are antineoplastic medicines and the monoindole alkaloids ajmalicine and serpentine are antihypertension drugs. C. roseus cell cultures have been studied for producing these medicines or precursors catharanthine and vindoline for almost four decades but so far without a commercially successful process due to biological and technological limitations. The research thus focused on the one hand on engineering the bioreactor process on the other engineering the cell factory itself. This review mainly summarizes the progress made on biochemical engineering aspects of C. roseus cell cultures in bioreactors in the past decades and metabolic engineering of indole alkaloid production in recent years. The paper also attempts to highlight new strategies and technologies to improve alkaloid production and bioreactor performance. Perspectives of metabolic engineering to create new cell lines for large-scale production of indole alkaloids in bioreactors and effective combination of these up- and down-stream processing are presented.

Keywords

Bioreactor process Catharanthus roseus Cell factory Gas regime Indole alkaloid Large-scale cell culture Metabolic engineering Monitoring and autocontroling 

Abbreviations

ABA

Abscisic acid

ABC transporter

ATP-binding cassette transporter

ASa

Anthranilate synthase α-subunit

DCO2

Dissolved carbon dioxide in liquid medium

DO2

Dissolved oxygen in liquid medium

KLa

Oxygen mass transfer coefficient

MeJA

Methyl jasmonate

SG

Strictosidine glucosidase

STR

Strictosidine synthase

TDC

Tryptophan decarboxylase

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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Department of Pediatrics, Children’s Nutrition Research CenterBaylor College of MedicineHoustonUSA
  2. 2.Section of Metabolomics, Division of Pharmacognosy, Institute of BiologyLeiden UniversityLeidenThe Netherlands

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