Industrial-scale fermentation

Table 8.5 Raw materials costs for industrial scale fermentation of L-phenylalanine.

Figure 5.8 Typical industrial-scale fermentation equipment as employed in the biopharmaceutical sector (a). Control of the fermentation process is highly automated, with all fermentation parameters being adjusted by computer (b). Photographs (a) and (b) courtesy of SmithKline Beecham Biological Services, s.a., Belgium. Photograph (c) illustrates the inoculation of a laboratory-scale fermenter with recombinant microorganisms used in the production of a commercial interferon preparation. Photograph (c) courtesy of Pall Life Sciences, Dublin, Ireland...

The industrial scale fermentative synthesis of PHA uses these pathways to convert the typical nutrients sugar or starch to PHB, but glycerol or palm-oil can also be applied. In addition, copolymers can be produced in this way but special microorganisms, growing condition, and additives are needed. Thus a statistic comonomer distribution starting from 0% (pure PHB) up to 90% co-monomer content can be achieved [35-38]. 

Figure 3.14. (a) Typical industrial-scale fermentation equipment as employed in the biopharmaceutical... 

The technology for their use, industrial-scale fermentation equipment, is already available (see Section 12.8.1). 

Figure 9.6 Examples of fermenters, (a) Large-scale fermenter for the production of ethanol (Copsright Lurgi AG, Germany), (b) Hi -tech industrial scale fermenter only the top part with the connections for loading and downstream processing is shown, the lower part extends to the floor below (right). Source Lonza Biologies Portsmouth USA)...

Cherry, G.B. McCann, E.P. Parker, A. The removal of bacteria from air by filtration application to industrial-scale fermentations. J. Appl. Chem. 1951, I, S103. 

As has been shown already on an Industrial scale, fermentation can be substituted by heterogeneous catalysts with resting microbial cells Immobilized In polymeric carriers. Repeated use of the once formed biomass, continuous process operation, and elimination of costly separation steps of product solution from biomass are obvious advantages of this new technology. Some principal aspects of a) Immobilization methodology, b) catalyst effectiveness, and c) operational stability shall be outlined In this contribution. 

For the production of natural products on an industrial scale, fermentation processes are often preferable in comparison to chemical processes. In biosynthesis processes, natural products may be generated efficiently and cleanly via enzymatic catalysis 185). Thus, the development of synthesis approaches similar to their biosynthesis is one of the main objectives of the synthesis community. To pursue this goal, Yokoyama and co-workers developed a bio-similar three-step synthesis of optically active clavicipitic acid (175) 186), which was isolated from natural sources as an isomeric mixture (Scheme 4.10) 187). 

Abdel-Fattah, W. R., Fadil, M., Nigam, R, Banat, 1. M. (2000). Isolation of theraiotoler-ant ethanologenic yeasts and use of selected strains in industrial scale fermentation in an Egyptian distiUery. Biotechnology and Bioengineering, 68, 531-535. 

Specific chemicals from industrial-scale fermentation processes Use of greater molecular diversity... 

Table 10.1 Comparison between a laboratory and industrial scale fermenter heat transfer...

Table 10.2 Comparison of laboratory and industrial scale fermenters power of agitation...

Since Enviromnental conditions can alter the evolutionary landscape so radically, the repeatability of EvoEng projects rely considerably on an experimenter s ability to control and report culture conditions (selection pressure). Furthermore, in industrial-scale fermentations repeatabihty can be the most essential quality of a robust production strain. This starts by cultivating investigations as close to industrial conditions as possible. This includes, but is not limited to aeration, carbon sources, nutrient sources, pH, osmolarity, temperature, light-exposure, or cell deusity. 

Most people are not aware of how deeply biotechnology products manufactured by large-scale fermentation, both recombinant and nonrecombinant, have affected our daily lives. The general public may be aware of the classical antibiotics or of large recombinant therapeutic proteins such as antibodies produced by industrial-scale fermentation. However, the role of fermentation for small-molecule pharmaceuticals, steroids, or cytotoxics is generally not known, let alone the role of fermentation for products used in flavors and fragrances, household appliances, chemical manufacturing, and many other markets. 

Laboratory-scale fermentations have been described elsewhere [2]. In this chapter, we lead the reader through the most important aspects of industrial-scale fermentation. Which organisms are suitable for large-scale suspension culture What do standard operating procedures (SOPs) and installations for large fermentation look like Which are the most important markets What affects the economics of large-scale fermentation, and which are the important regulatory aspects to be considered ... 

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