Fermentation vessels large

A bioreactor is a vessel in which an organism is cultivated and grown in a controlled manner to form the by-product. In some cases specialised organisms are cultivated to produce very specific products such as antibiotics. The laboratory scale of a bioreactor is in the range 2-100 litres, but in commercial processes or in large-scale operation this may be up to 100 m3.4,5 Initially the term fermenter was used to describe these vessels, but in strict teims fermentation is an anaerobic process whereas the major proportion of fermenter uses aerobic conditions. The term bioreactor has been introduced to describe fermentation vessels for growing the microorganisms under aerobic or anaerobic conditions. 

The control of these and any other parameters is most usually done in fermenter vessels specifically designed for the purpose and accommodating various working volumes, depending on the yield and production requirements. Laboratory-scale vessels could have a capacity of just 10 litres or less whereas clinical trials and production vessels may be as large as several thousand litres. 

The initial approach to recombinant insulin production taken entailed inserting the nucleotide sequence coding for the insulin A- and B-chains into two different E. coli cells (both strain K12). These cells were then cultured separately in large-scale fermentation vessels, with subsequent chromatographic purification of the insulin chains produced. The A- and B-chains are then incubated together under appropriate oxidizing conditions in order to promote interchain disulfide bond formation, forming human insulin crb ... 

This nutrient solution is inoculated with 10% of a 3-day old initial culture and incubated in portions of 100 mL. in 500-mL. Erlenmeyer flasks at 23 ° C. on a reciprocating shaking machine. A large scale culture may be grown in a similar manner in a stainless steel fermentation vessel containing 170 L. of nutrient medium. Aeration is effected... 

Fermentation vessels tend to be large because reaction rates are low. Typical batch reaction times are measured in days. Freely suspended mammalian cells are cultivated in conventionally agitated reactors up to 20,000 L in volume. Ethanol production with freely suspended yeast uses vessels 100 times larger, and wastewater treatment by the activated sludge process or in lagoons can be larger by another factor of 100. 

An unusual extraction procedure is shown in Scheme 6 for the purification of soraphen Aj from a myxobacterium. An adsorbent resin was added to a large-scale fermentation vessel prior to inoculation so that the metabolite was continuously adsorbed as it was produced. Not only did this simplify the isolation, but it also resulted in increased production of the compound by the organism, possibly because adsorbent effectively removed metabolite from the system, thus reducing any feedback inhibition. The eluate from the resin was sufficiently clean that it required only solvent extraction prior to a crystallization step that yielded reasonably pure soraphen A[ (8). 

Fig. 19.5 Large outdoor fermentation vessel (USP 3, 374, 726). 1. Tank 2. Cooling jacket 3. Foamed-synthetic resin 4. Manhole 5. Beer drainage cock 6. Beer feed pipe 7. Beer discharge pipe (pivoted) 8. Exhaust pipe 9. Siphon breaker 10. Pressure relief valve 11. Vacuum breaker 12. Thermometer and liquid depth senser 13. Water and detergent supply pipe 14. Water and detergent spray.

Returning to the question of costs of vessels, in general the greater the volume to surface area, the less expensive the unit volume cost should be. Fig. 19.8 illustrates this with respect to several types of large fermenting vessel. It was originally believed that spheroconical vessels would be prohibitively expensive to construct because of special fabrication difficulties. However such vessels have been successfully manufactured and used in Spain [39]. 

Growing market competition and an effort to achieve greater profitability led the brewing companies to implement large fermentation vessels (CCVs), in which intensified fermentation and maturation processes take place (Fignre 20.2). The CCVs... 

A wide variety of products can be produced by fermentation. In some cases the microorganism itself is the product, for example, in the manufacturing of active dry yeast (ADY). Well-known pharmaceutical fermentation products are insulin and penicillin G. Fermentation processes are also used to produce various commodity bioproducts like organic and amino acids, polysaccharides, lipids, chemical compounds like isoprene (Whited et al., 2010), 1,3-propanediol (Nakamura and Whited, 2003), RNA, DNA, enzymes, and other proteins. The large variety of commodity bioproducts produced by fermentation requires an equally large variety of different methods to separate and purify them. Compared to fermentation processes, where usually one unit, the fermenter vessel, is used, several different steps and unit operations are necessary to achieve purification and formulation of bioproducts. 

Large-scale commercial production of PHAs uses fermentation technologies. A generic process for PHA produced by bacterial fermentation consists of three basic steps fermentation, isolation and pirrification, and blending and palletizing [13]. Subsequent to inoculation and small-scale fermentation, a large fermentation vessel is filled with mineral medium and... 

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