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

Abstract

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.

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Abbreviations

AS:

Anthranilate synthase

BA:

Benzyl adenine

DI :

Diameter of the impeller

DO:

Dissolved oxygen concentration

DW:

Dry weight

FW:

Fresh weight

g :

Gravitational acceleration

G10H:

Geraniol 10-hydroxylase

IAA:

Indole-3-acetic acid

kLa:

Mass transfer coefficient

MIA:

Monoterpenoid indole alkaloid

μ:

Viscosity of the culture

N:

Agitation rate

Pmo :

Power dissipated by the impeller in absence of aeration

ppm:

Parts per million

ρ:

Density of the culture

rpm:

Revolutions per minute

SG:

Strictosidine β-glucosidase

SSS:

Strictosidine synthase

TDC:

Tryptophan decarboxylase

VOCs:

Volatile organic compounds

vol:

Volume

vvm:

Volume of gas per volume of culture per minute

wt:

Weight

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Lee-Parsons, C.W.T. Gas composition strategies for the successful scale-up of Catharanthus roseus cell cultures for the production of ajmalicine. Phytochem Rev 6, 419–433 (2007). https://doi.org/10.1007/s11101-006-9046-9

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Keywords

  • Carbon dioxide
  • Dissolved oxygen
  • Ethylene
  • Gaseous metabolites
  • Monoterpenoid indole alkaloids