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1.
Plant cell suspension cultures and hairy roots are potential sources of secondary metabolites and recombinant proteins. In
contrast to traditionally grown “whole wild plants” or “whole transgenic plants”, their production in bioreactors guarantees
defined controlled process conditions and therefore minimizes or even prevents variations in product yield and quality, which
simplifies process validation and product registration. Moreover, bioreactors and their configuration significantly affect
cultivation results by accomplishing and controlling the optimum environment for effective cell growth and production of bioactive
substances. This review highlights the main design criteria of the most widely used bioreactor types, both for plant cell
suspension cultures and for hairy roots, and outlines suitable low-cost disposable bioreactors which have found increasing
acceptance over the last 10 years.
Plants for human health in the post-genome era, PSE congress 26.8.2007–29.8.2007, Helsinki. 相似文献
2.
N. T. Thanh H. N. Murthy D. M. Pandey K. W. Yu E. J. Hahn K. Y. Paek 《Biologia Plantarum》2006,50(4):752-754
The effects of carbon dioxide supply within the range of 1–5 % (along with purified air), on cell culture of Panax ginseng were investigated in a balloon type bubble bioreactor containing 4 dm3 of Murashige and Skoog (MS) medium supplemented with 7.0 mg dm−3 indolebutyric acid, 0.5 mg dm−3 kinetin and 30 g dm−3 sucrose. A 1 % CO2 supply was found beneficial for the production of cell mass; however, increasing CO2 concentration to 2.5 and 5 % decreased the biomass accumulation. CO2 enrichment was not beneficial for saponin production and 1, 2.5, and 5 % CO2 supply resulted in decrease in saponin accumulation up to 11.6, 19.5, and 50.6 %, respectively. 相似文献
3.
Saurabh Chattopadhyay Sunita Farkya Ashok K. Srivastava Virendra S. Bisaria 《Biotechnology and Bioprocess Engineering》2002,7(3):138-149
Plant cell culture provides a viable alternative over whole plant cultivation for the production of secondary metabolites.
In order to successfully cultivate the plant cells at large scale, several engineering parameters such as, cell aggregation,
mixing, aeration, and shear sensitivity are taken into account for selection of a suitable bioreactor. The media ingredients,
their concentrations and the environmental factors are optimized for maximal synthesis of a desired metabolite. Increased
productivity in a bioreactor can be achieved by selection of a proper cultivation strategy (batch, fed-batch, two-stageetc.), feeding of metabolic precursors and extraction of intracellular metabolites. Proper understanding and rigorous analysis
of these parameters would pave the way towards the successful commercialization of plant cell bioprocesses. 相似文献
4.
Plant secondary metabolism is very important for traits such as flower color, flavor of food, and resistance against pests
and diseases. Moreover, it is the source of many fine chemicals such as drugs, dyes, flavors, and fragrances. It is thus of
interest to be able to engineer the secondary metabolite production of the plant cell factory, e.g. to produce more of a fine
chemical, to produce less of a toxic compound, or even to make new compounds, Engineering of plant secondary metabolism is
feasible nowadays, but it requires knowledge of the biosynthetic pathways involved. To increase secondary metabolite production
different strategies can be followed, such as overcoming rate limiting steps, reducing flux through competitive pathways,
reducing catabolism and overexpression of regulatory genes. For this purpose genes of plant origin can be overexpressed, but
also microbial genes have been used successfully. Overexpression of plant genes in microorganisms is another approach, which
might be of interest for bioconversion of readily available precursors into valuable fine chemicals. Several examples will
be given to illustrate these various approaches. The constraints of metabolic engineering of the plant cell factory will also
be discussed. Our limited knowledge of secondary metabolite pathways and the genes involved is one of the main bottlenecks.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
5.
刺激剂(elicitor)在植物细胞培养中被用来作为提高次生代谢物产量的手段。文中概括介绍了微生物、寡聚糖、蛋白质、第二信使及其他物质作为刺激剂在植物细胞培养中的应用及其研究成果。 相似文献
6.
Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals 总被引:10,自引:0,他引:10
R. Verpoorte R. van der Heijden H.J.G. ten Hoopen J. Memelink 《Biotechnology letters》1999,21(6):467-479
The technology of large-scale plant cell culture is feasible for the industrial production of plant-derived fine chemicals. Due to low or no productivity of the desired compounds the economy is only in a few cases favorable. Various approaches are studied to increase yields, these encompass screening and selection of high producing cell lines, media optimization, elicitation, culturing of differentiated cells (organ cultures), immobilization. In recent years metabolic engineering has opened a new promising perspectives for improved production in a plant or plant cell culture. 相似文献
7.
H. J. G. ten Hoopen W. M. van Gulik J. J. Heijnen 《In vitro cellular & developmental biology. Plant》1992,28(3):115-120
Summary Continuous culture is an attractive research tool in physiologic and growth and production kinetics research. However, fulfillment
of the basic assumptions of continuous culture in the experimental set-up may cause problems. The homogeneity of plant cell
cultures and effluent, particularly, may cause problems. This paper presents an experimental set-up which solves these problems
and describes the use of this equipment in a study of the growth kinetics of plant cells. Industrial application of the continuous
culture of plant cells in the production of secondary metabolites seems to be profitable when compared with batch or fed-batch
cultures. However, various problems such as uncoupled product formation and strain instability make fed-batch culture a better
choice.
Presented in the Session-in-Depth Batch Production and Fermentation at the 1991 World Congress on Cell and Tissue Culture,
Anaheim, California, June 16–20, 1991. 相似文献
8.
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10.
Two key issues in the application of plant-cell-culture technology to the production of valuable secondary metabolites are reviewed: the selection of cell lines with suitable genetic, biochemical and physiological characteristics; and the optimization of bioreactor environments. Although great progress has been made in recent years in the design, selection and optimization of bioreactor hardware, optimization of environmental factors such as medium components, light irradiation and O2 supply needs detailed investigations for each case. With a better understanding of plant cell metabolism and physiology, further developments in cultivation processes, such as process integration and on-line monitoring and control, can be expected in the near future.J.-J. Zhong and J.-T. Yu are with the Research Institute of Biochemical Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China T. Yoshida is with the International Center of Cooperative Research in Biotechnology (ICBiotech), Faculty of Engineering, Osaka University, Suita, Osaka 565, Japan. 相似文献
11.
Podophyllotoxin is an aryltetralin lignan synthesized in several plant species, which is used in chemotherapies for cancers and tumor treatment. More potent semisynthetic derivatives of podophyllotoxin such as etoposide and teniposide are being developed and evaluated for their efficacy. To meet the ever increasing pharmaceutical needs, species having podophyllotoxin are uprooted extensively leading to the endangered status of selective species mainly Sinopodophyllum hexandrum. This has necessitated bioprospection of podophyllotoxin from different plant species to escalate the strain on this endangered species. The conventional and non-conventional mode of propagation and bioprospection with the integration of biotechnological interventions could contribute to sustainable supply of podophyllotoxin from the available plant resources. This review article is focused on the understanding of different means of propagation, development of genomic information, and its implications for elucidating podophyllotoxin biosynthesis and metabolic engineering of pathways. In addition, various strategies for sustainable production of this valuable metabolite are also discussed, besides a critical evaluation of future challenges and opportunities for the commercialization of podophyllotoxin. 相似文献
12.
Terrier B Courtois D Hénault N Cuvier A Bastin M Aknin A Dubreuil J Pétiard V 《Biotechnology and bioengineering》2007,96(5):914-923
The present article describes two novel flexible plastic-based disposable bioreactors. The first one, the WU bioreactor, is based on the principle of a wave and undertow mechanism that provides agitation while offering convenient mixing and aeration to the plant cell culture contained within the bioreactor. The second one is a high aspect ratio bubble column bioreactor, where agitation and aeration are achieved through the intermittent generation of large diameter bubbles, "Taylor-like" or "slug bubbles" (SB bioreactor). It allows an easy volume increase from a few liters to larger volumes up to several hundred liters with the use of multiple units. The cultivation of tobacco and soya cells producing isoflavones is described up to 70 and 100 L working volume for the SB bioreactor and WU bioreactor, respectively. The bioreactors being disposable and pre-sterilized before use, cleaning, sterilization, and maintenance operations are strongly reduced or eliminated. Both bioreactors represent efficient and low cost cell culture systems, applicable to various cell cultures at small and medium scale, complementary to traditional stainless-steel bioreactors. 相似文献
13.
High‐throughput miniaturized bioreactors for cell culture process development: Reproducibility,scalability, and control 下载免费PDF全文
Shahid Rameez Sigma S. Mostafa Christopher Miller Abhinav A. Shukla 《Biotechnology progress》2014,30(3):718-727
Decreasing the timeframe for cell culture process development has been a key goal toward accelerating biopharmaceutical development. Advanced Microscale Bioreactors (ambr?) is an automated micro‐bioreactor system with miniature single‐use bioreactors with a 10–15 mL working volume controlled by an automated workstation. This system was compared to conventional bioreactor systems in terms of its performance for the production of a monoclonal antibody in a recombinant Chinese Hamster Ovary cell line. The miniaturized bioreactor system was found to produce cell culture profiles that matched across scales to 3 L, 15 L, and 200 L stirred tank bioreactors. The processes used in this article involve complex feed formulations, perturbations, and strict process control within the design space, which are in‐line with processes used for commercial scale manufacturing of biopharmaceuticals. Changes to important process parameters in ambr? resulted in predictable cell growth, viability and titer changes, which were in good agreement to data from the conventional larger scale bioreactors. ambr? was found to successfully reproduce variations in temperature, dissolved oxygen (DO), and pH conditions similar to the larger bioreactor systems. Additionally, the miniature bioreactors were found to react well to perturbations in pH and DO through adjustments to the Proportional and Integral control loop. The data presented here demonstrates the utility of the ambr? system as a high throughput system for cell culture process development. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:718–727, 2014 相似文献
14.
Wei Yue Qian-liang Ming Bing Lin Khalid Rahman 《Critical reviews in biotechnology》2016,36(2):215-232
The development of plant tissue (including organ and cell) cultures for the production of secondary metabolites has been underway for more than three decades. Plant cell cultures with the production of high-value secondary metabolites are promising potential alternative sources for the production of pharmaceutical agents of industrial importance. Medicinal plant cell suspension cultures (MPCSC), which are characterized with the feature of fermentation with plant cell totipotency, could be a promising alternative “chemical factory”. However, low productivity becomes an inevitable obstacle limiting further commercialization of MPCSC and the application to large-scale production is still limited to a few processes. This review generalizes and analyzes the recent progress of this bioproduction platform for the provision of medicinal chemicals and outlines a range of trials taken or underway to increase product yields from MPCSC. The scale-up of MPCSC, which could lead to an unlimited supply of pharmaceuticals, including strategies to overcome and solution of the associated challenges, is discussed. 相似文献
15.
Ronald A. Taticek Murray Moo-Young Raymond L. Legge 《Plant Cell, Tissue and Organ Culture》1991,24(2):139-158
The enormous versatility of plants has continued to provide the impetus for the development of plant tissue culture as a commercial production strategy for secondary metabolites. Unfortunately problems with slow growth rates and low products yields, which are generally non-growth associated and intracellular, have made plant cell culture-based processes, with a few exceptions, economically unrealistic. Recent developments in reactor design and control, elicitor technology, molecular biology, and consumer demand for natural products, are fuelling a renaissance in plant cell culture as a production strategy. In this review we address the engineering consequences of the unique characteristics of plant cells on the scale-up of plant cell culture.Abbreviations a
gas-liquid interfacial area per volume
- C
dissolved oxygen concentration
- C*
liquid phase oxygen concentration in equilibrium with the partial pressure of oxygen in the bulk gas phase
- KL
overall mass transfer coefficient
- kL
liquid film mass transfer coefficient
- mO2
cell maintenance coefficient for oxygen
- OTR
oxygen transfer rate
- OUR
oxygen uptake rate
- pO2
partial pressure of oxygen
- STR
stirred-tank reactor
- v.v.m.
volume of gas fed per unit operating volume of reactor per minute
- X
biomass concentration
- Yx/O2
biomass yield coefficient for oxygen
-
specific growth rate 相似文献
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17.
It has been suggested that plant cell culture is the most suitable system for producing small-to-medium quantities of specialized, expensive, and high-purity proteins. Here, we report that a heterodimeric protein, human interleukin-12 (hIL-12), was expressed and secreted into culture medium in a biologically active form. A transgenic plant expressing hIL-12 was constructed by sexual crossing of plants that expressed each subunit of the protein. From a piece of transgenic plant, callus was induced and cell suspension culture was established. The biological activity and amount of hIL-12 secreted into culture medium were analyzed using bioassays and ELISA. Analysis of cellular localization demonstrated that the protein was secreted into the culture medium together with its intrinsic signal peptide. 相似文献
18.
We report for the first time that culture conditions, specifically culture medium supplementation with nucleotide-sugar precursors, can alter significantly the N-linked glycosylation of a recombinant protein in plant cell culture. Human secreted alkaline phosphatase produced in tobacco NT1 cell suspension cultures was used as a model system. Plant cell cultures were supplemented with ammonia (30 mM), galactose (1 mM) and glucosamine (10 mM) to improve the extent of N-linked glycosylation. The highest levels of cell density and active extracellular SEAP in supplemented cultures were on average 260 g/L and 0.21 U/mL, respectively, compared to 340 g/L and 0.4 U/mL in unsupplemented cultures. The glycosylation profile of SEAP produced in supplemented cultures was determined via electrospray ionization mass spectrometry with precursor ion scanning and compared to that of SEAP produced in unsupplemented cultures. In supplemented and unsupplemented cultures, two biantennary complex-type structures terminated with one or two N-acetylglucosamines and one paucimannosidic glycan structure comprised about 85% of the SEAP glycan pool. These three structures contained plant-specific xylose and fucose residues and their relative abundances were affected by each supplement. High mannose structures (6-9 mannose residues) accounted for the remaining 15% glycans in all cases. The highest proportion (approximately 66%) of a single complex-type biantennary glycan structure terminated in both antennae by N- acetylglucosamine was obtained with glucosamine supplementation versus only 6% in unsupplemented medium. This structure is amenable for in vitro modification to yield a more human-like glycan and could serve as a route to plant cell culture produced therapeutic glycoproteins. 相似文献
19.
Taxol production in bioreactors: Kinetics of biomass accumulation, nutrient uptake, and taxol production by cell suspensions of Taxus baccata 总被引:8,自引:0,他引:8
Srinivasan V Pestchanker L Moser S Hirasuna TJ Taticek RA Shuler ML 《Biotechnology and bioengineering》1995,47(6):666-676
The kinetics of biomass accumulation, nutrient uptake and taxol production of Taxus baccata cell suspensions were examined in three bioreactor configurations, viz. 250-mL Erienmeyerflasks, 1-L working volume pneumatically mixed (PMB), and stirred tank (STB) bioreactors. Qualitatively similar kinetics were observed in all three bioreactor types. Biomass accumulation and specific nutrient uptake rates exhibited biphasic characteristics. Carbohydrate uptake and biomass accumulation substantially ceased when phosphate was depleted from the medium. Phosphate was identified as a possible growth-limiting nutrient. Taxol accumulated exclusively in the second phase of growth. A maximum taxol concentration of 1.5 mg/L was obtained in the PMB which was fivefold greater than that obtained in the Erienmeyer flasks and the STB, but the relative kinetics of taxol production was the same in all three reactor types. Biomass yields were calculated from the kinetic data and a stoichiometry for biomass formation was evaluated. The similarity of kinetics in the three bioreactor configurations suggests that taxol production by T. baccata cell suspensions is amenable to scateup. (c) 1995 John Wiley & Sons, Inc. 相似文献
20.
Glycosyltransferases are members of the multigene superfamily in plants that can transfer single or multiple activated sugars
to a range of plant molecules, resulting in the glycosylation of plant compounds. Although the activities of many glycosyltransferases
and their products have been recognized for a long time, only in recent years were some glycosyltransferase genes identified
and a few functionally characterized in detail. Glycosylation is thought to be one of the most important modification reactions
towards plant secondary metabolites, and plays a key role in maintaining cell homeostasis, thus likely participating in the
regulation of plant growth, development and in defense responses to stress environments. With advances in plant genome projects
and the development of novel technologies in analyzing gene function, significant progress could be made in gaining new insights
into the properties and precise biological roles of plant secondary product glycosyltransferases, and the new knowledge will
have extensive application prospects in the catalytic synthesis of glycoconjugates and metabolic engineering of crops. In
this review, we summarize the current research, highlighting the possible biological roles, of plant secondary metabolite
glycosyltransferases and discuss their potential applications as well as aspects to be further studied in the near future. 相似文献