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

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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.

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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

K L a :

Oxygen mass transfer coefficient

MeJA:

Methyl jasmonate

SG:

Strictosidine glucosidase

STR:

Strictosidine synthase

TDC:

Tryptophan decarboxylase

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Acknowledgements

We thank guest editor to give us the chance to express and exchange our ideas with this research community. Although there are many other excellent publications on bioreactor processing Catharanthus roseus cell culture and related aspects, we regret not be able to cite them due to space limitation.

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Authors and Affiliations

  1. Department of Pediatrics, Children’s Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Room 9016, Houston, TX, 77030, USA

    Jian Zhao

  2. Section of Metabolomics, Division of Pharmacognosy, Institute of Biology, Leiden University, 2300 RA, Leiden, The Netherlands

    Robert Verpoorte

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  1. Jian Zhao
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  2. Robert Verpoorte
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Correspondence to Jian Zhao.

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Zhao, J., Verpoorte, R. Manipulating indole alkaloid production by Catharanthus roseus cell cultures in bioreactors: from biochemical processing to metabolic engineering. Phytochem Rev 6, 435–457 (2007). https://doi.org/10.1007/s11101-006-9050-0

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  • DOI: https://doi.org/10.1007/s11101-006-9050-0

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