Bacterial fermentation system

The basic process technology in vaccine production consists of fermentation for the production of antigen, purification of antigen, and formulation of the final vaccine. In bacterial fermentation, technology is weU estabHshed. For viral vaccines, ceU culture is the standard procedure. Different variations of ceU line and process system are in use. For most of the Hve viral vaccine and other subunit vaccines, production is by direct infection of a ceU substrate with the vims. 

Purification of biopharmaceuticals often involves the removal of materials with physical characteristics very similar to the desired product, such as failure sequences from DNA synthesis or misfolded proteins from bacterial fermentations. The contaminants, however, may have biological characteristics very different from the desired product, including different antigenicities, bioactivities, and specificities. There are even systems in which the... 

Extraction of PHA from plants is likely to be a major factor affecting the production cost of PHA from crops and, therefore, the economic viability of this approach. In contrast to production of PHA from bacterial fermentation, where the production system is designed to produce only PHA, an agricultural production of PHA is likely to be most viable only through the recovery of not only PHA but also all other useful components of the harvested crop, i.e., oil, proteins, and carbohydrates. This fact, combined with the lower level of PHA accumulation in plants in comparison to micro-organism, is likely to make PHA recovery from plants a challenging task. 

Over half of all biopharmaceuticals thus far approved are produced in recombinant E. coli or S. cerevisiae. Industrial-scale bacterial and yeast fermentation systems share many common features, an overview of which is provided below. Most remaining biopharmaceuticals are produced using animal cell culture, mainly by recombinant BHK or CHO cells (or hybridoma cells in... 

Hydrogen production from the bacterial fermentation of sugars has been examined in a variety of reactor systems. Hexose concentration has a greater effect on Hj yields than the HRT. Flocculation also was an important factor in the performance of the reactor (Van Ginkel and Logan, 2005). 

Over half of all biopharmacuticals thus far approved are produced in recombinant E. coli or S. cerevisiae. Industrial-scale bacterial and yeast fermentation systems share many common features, an overview of which is provided below. Most remaining biopharmaceuticals are produced using animal cell culture, mainly by recombinant BFIK or CFiO cells (or hybridoma cells in the case of some monoclonal antibodies Appendix 1). While industrial-scale animal cell culture shares many common principles with microbial fermentation systems, it also differs in several respects, as subsequently described. Microbial fermentation/animal cell culture is a vast speciality area in its own right. As such, only a summary overview can be provided below and the interested reader is referred to the Further Reading section. 

One of the most important sensors needed is one that reliably monitors cell density. An IR fiber-optic cell density probe has been used for this because it can directly monitor cell growth (without dilution) in high-cell-density bacterial fermentations. The ability to do an online sample filtration through the use of hollow fibers or rotating filters has made possible continuous, online measurement of glucose, lactate, and other metabolites. However, glucose, nitrogen substrate, and phosphate sensors that can withstand repeated system sterilization are still needed. 

Equations (1.3a) and (1.3b) illustrate the overall reactions of CO2 generation in aerobic and anaerobic respiration, respectively. Although not shown here, some types of bacterial fermentations can also be a source of CO2 for carbonate generation. Equation (1.5) explains the origin of C03 . This reaction is forced in the direction of C03 by loss of CO2 to the atmosphere in an open system, and by precipitation of calcium carbonate (CaC03), illustrated in Eq. (1.6), or by the formation of other carbonates not shown here. 

Chemistry. The cobalamin family consists of a corrin ring (Fig. 8.54). It is similar to that of the porphyrin ring system, except that there is no methylene or methine bridge between p3Trole rings A and D, and it contains cobalt rather than iron. The commercial form sold in the United States is cyanocobalamin. The hydroxy dosage form also has been used. The coenzyme forms include methyl and ad-enosyl cobalamin. The commercial vitamin is produced from bacterial fermentation. 

The volumetric productivity achievable in simple bioreactor systems when using bacterial expression systems is superior to that of mammalian expression systems. Growth rates are higher, and the ease of scale-up of the fermentation process enables manufacturing at scales up to five-fold larger compared to mammalian systems. 

The ability to clone and express commercially useful quantities of recombinant human proteins in bacterial, insect cell, yeast fermentation systems, or transgenic animals has enabled the development and introduction into the marketplace of otherwise unavailable lifesaving protein drugs. Numerous recombinant human protein and biotechnology products are in clinical trials or pending regulatory agency approval. 

Wakisaka, S., Y. Ohshima, M. Ogawa, T. Tochikura, andT. Tachiki. 1988. Characteristics and efficiency of glutamine production by coupling of a bacterial glutamine synthetase reaction with the alcoholic fermentation system of baker s yeast. Appl. Environ. Microbiol. 64 2953-2957. 

PolyChydroxyalkanoates), which are produced through bacterial fermentation, are one of the oldest examples of polymers produced via the biosynthetic pathway [75,76]. PolyChydroxyalkanoates) are essentially the energy reserves of anaerobic bacteria and are stored as granules in the cytoplasms of these organisms. In this system, hydrocarbons are converted into higher carbon-chain polyesters. Since monomers that can be processed by the bacteria are limited. 

The recovery of PHA plays a vital role in the overall production cost. Since PHA is an intracellular product, cell pretreatment and extraction methods are required to isolate and purify PHA from within bacterial cells, which has introduced additional cost to the PHA production process. The solvent extraction method is the most common and conventional way of PHA extraction. According to Chen and co-workers [1], this method could make up to 50% or more of the overall PHA manufacturing cost. Therefore, the downstream processing of PHA recovery is one of the key steps to ensure profitability of the fermentation system. 

Another complex polysaccharide which has been modified to enhance its properties is xanthan gum. Xanthan is a naturally produced bacterial exopolysaccharide of the etaxsXanthomonas. While many species of the genus will produce copious amounts of the polysaccharide, the model system for research and production is Xanthomonas campestris. Production is by bacterial fermentation using a media composed of 2.5 to 3% D-glucose, 0.4% dried distillers solubles, and simple salts (82). Within 96 hours 50% of the glucose is converted to xanthan. The cells are removed by centrifugation leaving the polysaccharide in solution. It is then precipitated by the addition of 50% (w/w) alcohol, often methanol or 2-propanol. The precipitate is dried and milled for commercial sale. 

---