Deep-tank fermentation

Fermentation. The microbial production of citric acid on a commercial scale was begun in 1923 utilizing certain strains yispergillus nigerio produce citric acid on the surface of a sucrose and salt solution. This tray fermentation technique is still used today, although it is being replaced by a submerged process known as deep tank fermentation (14—22). 

Fermenters with a capacity of over about 10 litres are too heavy to sterilise in autoclaves. Whilst they may still be laboratory-sized, they have to be constructed so that they may be sterilised in situ. They become, as a consequence, pressure vessels and the extensive use of glass becomes impractical and the preferred material of construction is a stainless steel. Seals are typically of silicone or other synthetic rubber or fluorinated plastics, with borosilicate glass being retained for sighting windows. This format is retained for vessels which are far larger than the laboratory scale, and Fig. 5.80 outlines the construction of a typical industrial deep tank fermenter. 

The most abundant bicyclic terpene in nature, x-pinene (14), has been the substrate for several microbiological transformation studies334,335. Aspergillus niger NCIM612, a strain selected from a number of fungal strains isolated from infected bark, exhibits maximum transformation capacity in shake cultures, with deep-tank fermentations being less successful. Transformation products of importance from (-)-x-pinene are 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol [( + )-rir-verbenol, 15, the major product], trimethylbicyclo[3.1.1]hept-3-en-2-one [(+ )-verbenone, 16] and 5-hydroxy-a,x,4-trimcthyl-3-cyclohexene-l-methanol [(+)-trao.s-sobrerol, 17]33S-337. 

Jackson M.L., Shen C.-C., Aeration and Mixing in Deep Tank Fermentation Systems, AIChE J. 24 (1978) 1,... 

Although both Aspergillus itaconicus and Aspergillus terreus are known producers of itaconic acid, the latter is superior to the former and is believed to be used industrially. Either surface (shallow-pan) or submerged (deep-tank) fermentation can be used. The medium contains molasses, cornsteep liquor. 

Neutral salts and aqueous solutions of various acids generally follow the acid action. Aluminum has no apparent action or microbiological processes (i.e., the production of antibiotics by deep-vessel fermentation). Fermentation tanks, as well as various absorbing and extracting units, can be made from aluminum. 

The most common procedure for large-scale aerobic fermentations is to use deep tanks of a stirred liquid medium. Efficient air exchange is obtained by continuous pumping of sterile air into crossed or coiled perforated pipe placed at the bottom of the tank at rates of up to one volume of air per unit of medium volume per minute [62]. This method promotes aerobic growth throughout the medium, which accomplishes large volume production in a limited space. But it also has problems, which relate to the maintenance of sterility and occasionally from foam formation. Overall, however, submerged... 

The engineer s contribution to the development of the penicillin fermentation was a very important one. The outgrowth of the undertaking was the pure-culture technique, carried out in aerated and agitated deep-tank fer-mentors. This technique, similar to its antecedent used for yeast propagation, introduced to the biochemical process industry refined fermentation equipment capable of being maintained under aseptic conditions even when vigorously aerated. The technique has now been applied widely with minor modifications to the production of other antibiotics, amino acids, steroids, enzymes, and therapeutic proteins. 

Eventually, 100,000 units of penicillin were produced by a consortium of American drug companies (Merck, Squibb, and Pfizer) by the middle of 1944. A tremendous improvement in yield was made possible by the use of a new strain of mold, as well as the use of deep fermentation tanks similar to those used in the brewery industry. Interestingly, the new strain of mold discovered was serendipitously found on a decaying cantaloupe in a Peoria food market. 

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