Essential Bioprocesses

When compared to purely chemical synthesis, bioprocesses are operated under relatively mild conditions and in aqueous solvents they are essentially low temperature processes with operating temperatures usually below 40°C. The pH of most bioprocesses is between 6 and 8 and the pressure is usually one atmosphere. Under these conditions, substrates (eg oxygen) can be poorly soluble in water, which may limit productivity. Since reactions can generate considerable amounts of heat, waste heat generated during bioprocesses often has to be adequately dissipated to ensure high temperatures do not damage enzymes or cells. 

When compared to traditional chemical synthesis, processes based on biocatalysts are generally less reliable. This is due, in part, to the fact that biological systems are inherently complex. In bioprocesses involving whole cells, it is essential to use the same strain from the same culture collection to minimise problems of reproducibility. If cell free enzymes are used the reliability can depend on the purity of the enzyme preparation, for example iso-enzyme composition or the presence of other proteins. It is, therefore, important to consider the commercial source of the enzyme and the precise specifications of the biocatalyst employed. 

Bioprocess plants are an essential part of food, fine chemical and pharmaceutical industries. Use of microorganisms to transform biological materials for production of fermented foods, cheese and chemicals has its antiquity. Bioprocesses have been developed for an enoimous range of commercial products, as listed in Table 1.1. Most of the products originate from relatively cheap raw materials. Production of industrial alcohols and organic solvents is mostly originated from cheap feed stocks. The more expensive and special bioprocesses are in the production of antibiotics, monoclonal antibodies and vaccines. Industrial enzymes and living cells such as baker s yeast and brewer s yeast are also commercial products obtained from bioprocess plants. 

High cell densities are not only a prerequisite for high productivity additionally an effective on-line control and modeling of the bioprocesses is necessary. For industrial applications, optical measurement methods are more attractive because they are non-invasive and more robust. The potential of the BioView sensor for on-line bioprocess monitoring and control was tested. For high-cell-density cultivation of Escherichia coli, maintaining aerobic conditions and removal of inhibitory by-products are essential. Acetic acid is known to be one of the critical metabolites. Information about changes in the cell metabolism and the time of important process operations is accessible on-line for optimization... 

Recently, an industrial process development for nootkatone production from valencene by microbial transformation (bacteria, fungi) was mentioned [199, 200]. Although no details were given, the author claimed the development of an in situ product-removal technique by which an extremely selective recovery of nootkatone from the reaction mixture and the excess precursor during the proceeding production was achieved and which was said to be essential for an economically viable bioprocess. 

Disparate elements, which affect economic decisions for bioprocesses, can be combined into a logical approach. An attempt must be made to combine fundamentals of bioreactor design, downstream processing, and properties of biomolecules in the context of process evaluation. The ability to set technical priorities based on economic assessment is essential, and requires communication betv/een researchers, process engineers, technical managers, and marketing managers. 

In plant cell cultures, shake flask culture is an indispensable stage of cultivation. Investigations in a shake flask are very essential and critical to bioprocess scale-up and optimization. We have developed a simple and convenient technique based on the principle of the Warburg manometric method to measure 02 uptake rate (OUR) and C02 evolution rate (CER) of suspended cells in a shake flask culture. This technique has been successfully applied to suspension cultures of Panax notoginseng cells, and some important bioprocess parameters, such as OUR, CER, respiratory quotient (RQ), SOUR and specific CER (SCER), were quantitatively obtained [99]. As long as the environment temperature is strictly controlled to within an error of 0.1 °C, the measuring system is accurate and reproducible, is easy to operate, is economical, and is also able to treat many samples simultaneously. 

Cellular activities such as those of enzymes, DNA, RNA and other components are the primary variables which determine the performance of microbial or cellular cultures. The development of specific analytical tools for measurement of these activities in vivo is therefore of essential importance in order to achieve direct analytical access to these primary variables. The focus needs to be the minimization of relevant disturbances of cultures by measurements, i. e. rapid, non-invasive concepts should be promoted in bioprocess engineering science [110,402]. What we can measure routinely today are the operating and secondary variables such as the concentrations of metabolites which fully depend on primary and operating variables. 

Fig. 20. Schematic design of linking a chromatograph on-line to bioprocesses. In principle, the design is almost identical to an FIA system. This is why FIA is often characterized as chromatography without a column. However, degassing of the sample is essential, in particular, when no internal standard is added (as in this sketch). In addition, the technical designs of injection valves differ and the injector to a gas chromatograph is heated to 200 or 250°C which means it needs, therefore, a special construction...

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