Kinetics of Growth and Product Formation

Mammalian growth usually shows respiratory quotients close to 1, that is, carbon dioxide formation (CER) equals oxygen uptake rate (OUR). With respect to the relatively poor mass transfer conditions installed in cell culture reactors (compared to microbial conditions), dissolved CO2 (dCOj) levels can accumulate during fed-batch processes. While optimum dC02 concentrations appear to be cell-specific, growth inhibiting partial pressures of approximately 100 mbar had been identified for, for example, hybridoma cells [81]. 

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A general scheme for the development of an industrial process for alkaloid production is depicted in Pig. 1. On the basis of both fundamental research and feasibility studies the decision can be made whether an industrial production process is achievable. For the design of the process (production volume, process type, bioreactor size and type) detailed knowledge of both the kinetics of growth and product formation and physical properties (rheology, shear sensitivity) is essential. 

To design a production process to obtain alkaloids from plant cell cultures with a promising productivity on a laboratory scale, detailed knowledge of the kinetics of growth and product formation of the cell culture is essential. In order to obtain a quantitative description of the behavior of the cell culture as a function of the external conditions, this knowledge is embedded in a mathematical model. On the basis of the model a process design can be made after which the economic feasibility of the process can be assessed. 

After implementation of the process the model is subsequently used in process control and optimization. The number of publications dealing with quantitative research on the kinetics of growth and product formation of cultured plant cells has been very limited. For the scarce kinetic research that has been reported batch cultures were used, which were mostly grown... 

From kinetics studies of unicellular organisms, a set of mathematical expressions have been established to represent the most frequent phenomena in bioprocesses. These phenomena involve a limitation or inhibition of growth and product formation, caused by the presence of substrates, products, or byproducts in culture media. Many of these expressions do not derive from known kinetic mechanisms. In fact, they are simply mathematical expressions with fitted parameters that are able to reproduce experimentally observed kinetic profiles. These equations have been derived and used in many unstructured microbial or cell models. 

Morris (616) showed the influence of culture temperature on the kinetics of growth and product formatioir in batch-cultured C. roseus cells. The cells were cultivated at temperatures of 15,25, and 35°C. At a temperature of 15°C growth and alkaloid formation were suppressed although they remained coupled, as was the case at the maintenance temperature of 25°C. At a temperature of 35°C no serpentine or ajmalicine accumulation occurred. A later paper (56) described a more detailed study performed on... 

These phenomena principally govern the performance of a bioreactor. The first and second of these phenomena are independent of scale. Neither a typical thermodynamic property (e.g., the solubility of oxygen in a broth) nor microkinetic properties (e.g., the growth and product formation by the microorganism) are dependent on the scale of the bioreactors. However, the actual oxygen concentrations and the kinetic behavior of microorganisms in a bioreactor are dependent on... 

Further study of the mass and heat transfer, the kinetics of substrate consumption, cell growth and product formation, estabhshment of a workable mathematical model for process scale up and optimization for sohd-state fermentation. 

Microbial activities like growth and product formations can be regarded as a sequence of enzymatic reactions. On this basis Ferret (1960) constructed a kinetic model for a growing bacterial cell population. The main pathways for major nutrients are considered together with pathways for minor nutrients and trace elements linked to each other. This metabolic network can be simplified with the aid of the concept of the rate-determining step (rds), resulting in a master reaction or bottleneck that limits the total flux and the rate of the process. 

Frolov, Shabanova, and co-workers (37-39) studied the transition of a sol into a gel and the aggregate stability of colloidal silica. Their aim was to develop a technology for the production of highly-concentrated silica sols and to use them as binders, catalyst supports, polymer fillers, adsorbents, and so forth. Kinetic studies were made of polycondensation and gel formation in aqueous solutions of silicic acids. At the stage of particle growth, poly condensation proceeds in the diffusion-kinetic region. With changes in pH, temperature, concentration, and the nature of electrolytes,... 

Wang J, Yue Z-B, Sheng G-P, Yu H-Q (2010) Kinetic analysis on the production of polyhydroxy-alkanoates from volatile fatty acids by Cupriavidus necator with a consideration of substrate inhibition, cell growth, maintenance, and product formation. Biochem Eng J 49 422-428 Wang Y, Yamada S, Asakawa N, Yamane T, Yoshie N, Inoue Y (2001) Comonomer compositional distribution and thermal and morphological characteristics of bacterial poly(3-hydroxybu-tyrate-co-3-hydroxyvalerate)s with high 3-hydroxyvalerate content. Biomacromolecules 2 1315-1323... 

Moser, A. (1980b). In Theoretical Basis of Kinetics of Growth, Metabolism and Product Formation of Microorganisms, Part 2. UNEP/UNESCO/ICRO Training Course, Zentralinstitut fiir Mikrobiologie und Experimentelle Therapie, Academy of Science, Jena, (Knorre W., ed.) East Germany (publisher) p. 27. 

Gutke, R. (1980). In UNEP/UNESCO/ICRO training course. Theoretical Basis of Kinetics of Growth, Metabolism and Product Formation of Microorganisms. Jena Science Academy of East Germany, Central Institute for Microbiology and Experimental Therapy (ZIMET), Vol. 1, pps. 30, and 112. 

Schmid G, Wilke CR, Blanch HW. (1992) Continuous hybridoma suspension cultures with and without cell retention kinetics of growth, metabolism and product formation. J. BiotechnoL, 22 31-40. 

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