Growth of Catharanthus roseus suspensions for maximum biomass and alkaloid accumulation

Scragg, Alan H.; Ashton, S.; York, Alan C.; Bond, P.; Stepan-Sarkissian, G.; Grey, D.

doi:10.1016/0141-0229(90)90101-u

Cited by 28 publications

(10 citation statements)

References 7 publications

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“…5A). The accumulation of serpentine in cell suspension cultures is also non-growth associated (Merillon et al, 1984;Morris, 1986;Scragg et al, 1990). The accumulation of ajmalicine was largely growth associated (Fig.…”

Section: Discussionmentioning

confidence: 93%

Transient studies of nutrient uptake, growth, and indole alkaloid accumulation in heterotrophic cultures of hairy roots ofCatharanthus roseus

Bhadra

Shanks

1997

Biotechnol. Bioeng.

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The kinetics of growth, the uptake of macronutrients, and the accumulation of indole alkaloids were investigated in long-term, heterotrophically cultured transgenic (''hairy'') roots of Catharanthus roseus. Tabersonine, ajmalicine, and serpentine were monitored over a 70-day period. The doubling time [dry-weight (DW) basis] of C. roseus hairy roots in B5/2 nutrients supplemented with 3% sucrose was 3.6 days. NH 4 + , NO 3 , − and P i were depleted sequentially from culture medium by hairy roots, while sugars remained undepleted. The growth-limiting nutrient was inorganic nitrogen, NH 4 + and NO 3 − , with exponential-phase overall biomass yields of 34.1 and 5.0 g DW/g nutrient, respectively. Extracellular pH decreased to 4.8 in early exponential phase of culture growth from the initially adjusted value of 5.7, increased subsequently to a maximum of 7.7 in late exponential phase of growth coincident with the maximum of fresh weight (FW)/DW ratio, before decreasing to 5.5-5.0. The organic acids, pyruvate, formate, lactate, and succinate were excreted by hairy roots starting in late phase of exponential growth, possibly resulting in the late-culture pH decrease. Tabersonine accumulation was distinctly growth associated with maximum specific and total yields of 1.15 mg/g DW and 5.6 mg/L, respectively, in late-exponential phase of growth. Serpentine accumulation was non-growth associated with increasing specific and total levels in stationary growth phase: 1.3 mg/g DW and 10.5 mg/L, respectively. The accumulation of ajmalicine also appeared growth associated.

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Section: Discussionmentioning

confidence: 93%

Transient studies of nutrient uptake, growth, and indole alkaloid accumulation in heterotrophic cultures of hairy roots ofCatharanthus roseus

Bhadra

Shanks

1997

Biotechnol. Bioeng.

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“…These reactors are appropriate for moderate plant cell concentrations, e.g., with cell concentrations of 10-15 g/L by dry weight (DW), but they are generally considered unsuitable for high density (more than 20 g DW/L) plant cell cultivations due to the serious problems in mixing and oxygen transfer (10). However, several recent studies suggest that whether high cell density available in a pneumatically agitated bioreactor is dependent on reactor design and operation mode at least (11). In another aspect, as demonstrated in the case of serpentine formation by Catharanthus roseus cells, the scale-up of the metabolite production process from a shake flask to an air-lift reactor was a big problem, even though the cells had similar growth rate and final biomass density for the two systems (7).…”

Section: Introductionmentioning

confidence: 99%

Improvement of Panax notoginseng Cell Culture for Production of Ginseng Saponin and Polysaccharide by High Density Cultivation in Pneumatically Agitated Bioreactors

Yao

Zhong

2001

Biotechnol. Prog.

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A Panax notoginseng cell culture was successfully scaled up from shake flask to 1.0-L bubble column reactor and concentric-tube airlift reactor. High-density bioreactor batch cultivation was carried out using a modified MS medium. The maximum cell density in batch cultures reached 20.1, 21.0 and 24.1 g/L in the shake flask, bubble column and airlift reactors, respectively, and their corresponding biomass productivity was 950, 1140 and 1350 mg/(L x d) for each. The productivity of ginseng saponin was 70, 96 and 99 mg/(L x d) in the flask, bubble column and airlift reactors, respectively; and the polysaccharide productivity reached 104, 119 and 151 mg/(L x d) for each. Furthermore, a fed-batch cultivation strategy was developed on the basis of specific oxygen uptake rate (SOUR), i.e., sucrose feeding before a sharp decrease of SOUR, and the highest cell density of 29.7 g/L was successfully achieved in the airlift bioreactor on day 17 with a very high biomass productivity of 1520 mg/(L x d). The concentrations of ginseng saponin and polysaccharide reached about 2.1 and 3.0 g/L, respectively, and their productivity was 106 (saponin) and 158 mg/(L x d) (polysaccharide). This work successfully demonstrated the high-density bioreactor cultivation of P. notoginseng cells in pneumatically agitated bioreactors and the reproduction of the shake flask culture results in bioreactors. The cell density, biomass productivity, production titer and productivity of both ginseng saponin and polysaccharide obtained here were the highest that have been reported on a reactor scale for all the ginseng species.

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“…Despite the many reports claiming to have demonstrated increased alkaloid production, one has to realize that the product levels have not been improved since the first findings 15-20 years ago. Thus, the product levels of bioreactor studies remain at 10-50 mg L-' ajmalicine or serpentine (corresponding to 0.1 to 0.5% of dry mass) SCRAGG et al, 1989;SCRAGG et al, 1990;SCHLATMANN et al, 1994). One reason for this undoubtedly poor progress could be the fact that most often only a single factor was analyzed at any one time.…”

Section: Fig 4 Monoterpene Indole Alkaloids Of Catharanthus Roseusmentioning

confidence: 99%

Secondary Products from Plant Cell Cultures

Berlin¹

2001

Biotechnology Set

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production of serotonin by suspension and root cultures of Peganum harmala transformed with a tryptophan decarboxylase cDNA from Catharanthus roseus, Transgen. Res. 2, 336-344. BERLIN, J., FECKER, S., HERMINGHAUS, C., RU-GENHAGEN (1994), Genetic modification of plant secondary metabolism: alteration of product levels by overexpression of amino acid decarboxylases, in: Advances in Plant Biotechnology. Studies in Plant Science, Vol. 4 (RYu, D. D. Y., FURASAKI, S., Eds.), pp. 57-81. Amsterdam: Elsevier. BIANCO-COLOMAS, J., HUGUES, M. (1990), Establishment and characterization of a betacyanin producing cell line of Amaranthus tricolor: Inductive effects of light and cytokinins, J. Plant Physiol. 136,734-739. mulation of phenolic conjugates and betacyanins, and changes in the activities of enzymes involved in feruloylglucose metabolism in cell suspension cultures of Chenopodium rubrum, Planta 184, 261-270. BREULING, M., ALFERMANN, A. W., REINHARD, E. (1985), Cultivation of cell cultures of Berberis wilsonae in 20-L airlift bioreactors, Plant Cell Rep. 4,220-223. BRINGI, V., KADKADE, P. (1993), Enhanced production of taxol and taxanes by cell cultures of T a u s species, WO 93/17121. BUITELAAR, R. M., LANGENHOFF, A. A. M., HEIDSTRA, R., TRAMPER, J. (1991), Growth and thiophene production by hairy root cultures of Tagetes patula in various two-liquid-phase bioreactors, Enzyme Microb. Technol. 13, 487-494. BUITELAAR, R. M., TRAMPER, J. (1992), Strategies to improve the production of secondary meta-Physiol. 86, 161-165.

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Growth of Catharanthus roseus suspensions for maximum biomass and alkaloid accumulation

Cited by 28 publications

References 7 publications

Transient studies of nutrient uptake, growth, and indole alkaloid accumulation in heterotrophic cultures of hairy roots ofCatharanthus roseus

Transient studies of nutrient uptake, growth, and indole alkaloid accumulation in heterotrophic cultures of hairy roots ofCatharanthus roseus

Improvement of Panax notoginseng Cell Culture for Production of Ginseng Saponin and Polysaccharide by High Density Cultivation in Pneumatically Agitated Bioreactors

Secondary Products from Plant Cell Cultures

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