Plant cell culture chemical

Rao SR, Ravishankar GA, Plant cell cultures Chemical factories of secondary metabolites, BiotechnolAdv 20 101—153, 2002. 

Ramachandra Rao, S. and Ravishankar, G.A., Plant cell cultures chemical factories of secondary metabolites, Biotechnol. Adv., 20, 101, 2002. 

PLATE 3 Cell culture of plants now takes place in individual containers cared for by hand. Automation of plant cell culture using chemical engineering techniques could improve the yields and economics of plant cell culture and expand the range of its applications in the production of new species and hybrids. Courtesy, Monsanto Company. 

Figure 12.4 The molecular structure of a taxane [114]. Taxotere is the semi-synthetic congener of Taxol. (Reproduced by permission from Macmillan Publishers Ltd Susan C. Roberts. Production and engineering of terpenoids in plant cell culture. Nature Chemical Biology 3 (7) 387-395. London Nature Publishing Group. 2007 Macmillan)...

Roberts, S. C. (2007) Production and engineering of terpenoids in plant cell culture. Nature Chemical Biology, 3,... 

Possible contamination by chemical or biological substances is one of the most important concerns when producing pharmaceutical proteins. Plant cell cultures ensure the production of the desired protein in a controlled, sterile and sealed environment and can be adapted to cGMP conditions. Therefore, the risk of contamination is minimized and the production conditions can be modified more easily in a contained reactor than in the field. Another advantage is the ability to freeze plant suspension cells in liquid nitrogen [66, 67] so that master and working cell banks can be established, a prerequisite for cGMP procedures [68]. 

Although plant cell culture is not as cost effective as plant cultivation in the open field, it will become an economical process if higher protein yields can be achieved [58]. The cultivation medium of plants is chemically defined, consisting of a carbon source, minerals, vitamins and phytohormones [69]. Furthermore, it is protein-free and relatively inexpensive. In contrast, animal cells often require complex supplements such as fetal calf serum and/or expensive growth factors, although serum-free cultivation is possible in case of Chinese hamster ovary (CHO) cells [70]. 

In recent years, extensive attention has been focused on finding cultured plant cells that can be used as catalysts for organic functional group transformations. A number of transformations employing freely suspended or immobilized plant cell cultures have been reported.24 For example, Akakabe et al.25 report that immobilized cells of Daucus carota from carrot can be used to reduce prochiral carbonyl substrates such as keto esters, aromatic ketones, and heterocyclic ketones to the corresponding secondary alcohols in ( -configuration with enantiomeric excess of 52-99% and chemical yields of 30 63%). 

Other kinds of plant cell cultures such as immobilized tobacco cells have also been studied for the analogous transformation. The results show that plant cell cultures provide an accessible way of converting several prochiral ketones into the corresponding chiral secondary alcohols with reasonable chemical yield and high enantioselectivity. 

Plant Cells and Tissues Structure-Function Relationships. Methods for the Cytochemical/Histochemical Localization of Plant Cell/Tissue Chemicals. Methods in Light Microscope Radioautography. Some Fluorescence Microscopical Methods for Use with Algal, Fungal, and Plant Cells. Fluorescence Microscopy of Aniline Blue Stained Pistils. A Short Introduction to Immunocytochemistry and a Protocol for Immunovi-sualization of Proteins with Alkaline Phosphatase. The Fixation of Chemical Forms on Nitrocellulose Membranes. Dark-Field Microscopy and Its Application to Pollen Tube Culture. Computer-Assisted Microphotometry. Isolation and Characterization of... 

A large number of various fine chemicals is derived from plants, e.g., drugs, pigments, and other biologically active substances. In the past, their production by means of plant cell cultures has attracted the interest of many researchers. Although most plant cell cultures have been unable to... 

Such information about shear effects in plant cell suspension cultures as given above is useful for bioreactor design and operation as well as the optimization of bioreactor environments for plant cell cultures. It may also be beneficial to bioreactor scale-up and high-density cultivation of plant cells for production of useful plant-specific chemicals (pharmaceuticals). In addition, because different cell suspensions can show different degrees of cell sensitivity to shear stress, and shear affects culture viability, cell lysis, and even metabolite secretion, as demonstrated in various cases like cell cultures of tobacco, Catharanthus roseus and Perilla frutescens [17, 54, 61], detailed studies are required for individual cases. 

Carbon dioxide is, of course, fundamentally important to plants because of photosynthesis. Most plant cell cultures are heterotrophic, non-photosynthetic and use a chemical energy source. It is reasonable to suspect, however, that some of the control mechanisms for the photosynthetic dark reactions would be regulated by C02 concentration. This could affect both cell growth and, indirectly, production of useful compounds. More concretely, C02 is known to promote synthesis of ethylene [38] on the other hand, C02 concentrations of 5-10% inhibit many ethylene effects [53]. 

To remove the feedback regulation mechanism and to avoid product degradation various adsorbents have been used for the in situ separation of plant cell cultures as shown in Table 1. In situ removal with polymeric adsorbents stimulated anthraquinone production more than the adsorbent-free control in Cinchona ledgeriana cells [35]. It was found that nonionic polymeric resins such as Amberlite XAD-2 and XAD-4 without specific functional groups are suitable for the adsorption of plant metabolite [36]. The use of the natural polymeric resin XAD-4 for the recovery of indole alkaloids showed that this resin could concentrate the alkaloids ajmalicine by two orders of magnitude over solvent extraction [37] but the adsorption by this resin proved to be relatively nonspecific. A more specific selectivity would be beneficial because plant cells produce a large number of biosynthetically related products and the purification of a several chemically similar solutes mixture is difficult [16]. 

The new technique introduced new potential sources for studying the production of medicinally important compounds, their metabolic pathways and chemical regulation92. Activity in plant cell culture research has been considerably increased in the last decade 93). This technique is used in studies on problems in plant propagation and crop improvement. Host-parasite relationship studies are facilitated... 

In this connection, I would like to cite three examples of chemical engineering challenges in biotechnology where, while an understanding of cell behavior is needed, it is the basic chemical engineering research that will likely make the difference. One example is from plant cell culture, the second from antibiotic production, and the third from biotechnology monitoring and control. 

One reason for interest in plant cell culture is that over 20,000 different chemicals are produced from plants, with about 1600 new plant chemicals added each year. Also, 25% of all prescribed drugs come from plants. These chemicals can be produced in a bioreactor through suspension culture. Advantages of plant cell suspension culture, as compared to agriculture, are that plant cell suspension culture can be carried out independently of weather conditions and political problems, it does not compete with other agricultural products for land use, and it is done in a controlled environment which minimizes contamination and provides easier product validation and assurance. 

Plant derived pharmaceuticals are estimated to have an annual value of 9 billion in the U.S. alone (4). Flavors and fragrances have a current worldwide market of about 1.5 billion. Market data for insecticides and other fine chemicals such as pigments are not readily available. The first example, and the only current commercial process based on plant cell culture, is for the production of shikonin in Japan. This compound is both used in medicine and as a pigment (5-7. ... 

Bioreactors employing plant cell cultures have use in chemicals production systems and in micropropagation (biomass) systems, as well. Factors related to the performance of these reactors from an engineering point of view have been addressed in this paper. Some preliminary data from our laboratory suggest how mass... 

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