Phytochemistry Reviews

, Volume 6, Issue 2–3, pp 419–433 | Cite as

Gas composition strategies for the successful scale-up of Catharanthus roseus cell cultures for the production of ajmalicine

  • Carolyn W. T. Lee-Parsons
Review Paper


Ajmalicine, serpentine, catharanthine, and vindoline are monoterpenoid indole alkaloids (MIAs) of commercial interest which are produced by the Catharanthus roseus plant. Cultures of C. roseus have been investigated as a potential source of these pharmaceutically important compounds since the early 1960s. In addition, their production from C. roseus cultures has served as a model system for investigating secondary metabolism and for evaluating production-enhancing strategies. Initially, this review will survey (1) the MIAs of interest for large-scale production from plant cell cultures and (2) the volumetric productivities of a specific MIA, ajmalicine, achieved and projected using plant cell cultures. To meet the need for these valuable compounds, the production of these MIAs from plant cell cultures must be successfully reproduced in large-scale aerated and agitated reactors. While the large-scale cultivation of plant cell cultures is currently feasible, initial attempts at scale-up may yield results that differ from that optimized in flasks. To bridge the jump between production in flasks and production in large-scale bioreactors, changes introduced with scale-up such as gas composition must be identified and rationally manipulated to reproduce or even improve growth and secondary metabolite production. Hence, this review will (1) identify the effects of gas composition (i.e., O2, CO2, ethylene, or other endogenous volatile compounds) on growth and secondary metabolism and (2) draw operating strategies for optimizing the gas composition for growth of C. roseus cultures and the production of ajmalicine.


Carbon dioxide Dissolved oxygen Ethylene Gaseous metabolites Monoterpenoid indole alkaloids 



Anthranilate synthase


Benzyl adenine


Diameter of the impeller


Dissolved oxygen concentration


Dry weight


Fresh weight


Gravitational acceleration


Geraniol 10-hydroxylase


Indole-3-acetic acid


Mass transfer coefficient


Monoterpenoid indole alkaloid


Viscosity of the culture


Agitation rate


Power dissipated by the impeller in absence of aeration


Parts per million


Density of the culture


Revolutions per minute


Strictosidine β-glucosidase


Strictosidine synthase


Tryptophan decarboxylase


Volatile organic compounds




Volume of gas per volume of culture per minute




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© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Chemical Engineering Department, 342 Snell Engineering CenterNortheastern UniversityBostonUSA

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