Rotary filter

Heat exchanger Holding tank

. to further purification

Shake flask vegetative growth

Figure 1.2. Penicillin cultivation process.

or Gram-negative bacteria but not both. Penicillin is an example of narrow spectrum antibiotic. Broad-spectrum antibiotics are active against a wide range of microorganisms such as both Gram-negative and Gram-positive bacteria. Tetracycline is an example of a broad-spectrum antibiotic.

The penicillin family includes penicillin G, penicillin V, penicillin O, and many synthetic and semisynthetic derivatives such as ampicillin, amoxicillin, nafcillin and ticarcilin. /^-lactams are the largest group of antibiotics covering approximately 65% of the World market. More than 60% of these antibiotics are penicillin derivatives (either penicillin V or penicillin G). The total worldwide production of bulk penicillin is about 25,000 tons of which about 70% is sold either directly, i.e. penicillin V for oral administration and penicillin G for use in animal feed mixtures or a sterile salt, or it is converted to amoxicillin and ampicillin via 6-APA [424].

Although penicillin is produced by many Pénicillium and Aspergillus strains, industrial penicillin is completely produced by Pénicillium chryso-genum. Highly developed mutants are also used in industry. The medium for penicillin production typically contains an organic nitrogen source (e.g. corn steep liquor), fermentable carbohydrate (e.g. sucrose, lactose, fructose, or glucose), calcium carbonate as a buffer and other inorganic salts as necessary. Oxygen should also be added not to exceed 40% of saturation which corresponds to a volumetric oxygen uptake rate of 0.4-0.8 mmol/l/min. Although it is strain-specific, pH and temperature of cultivation broth are typically between 5-7 and 23-28° C. respectively. The culture volume is 40,000-200,000 I and is vigorously agitated using turbine agitators. Under these circumstances, a maximum theoretical yield of penicillin on glucose is estimated to be 0.12 g penicillin/g glucose [26]. A typical industrial scale process for penicillin production is shown in Figure 1.2 starting with culture growth. Pénicillium chrysogenum strains are used to inoculate 100 ml of the medium in a 500 ml flask at 25°C. After incubating for four days, the contents of the flask are transferred to a new 2 I medium which is further incubated for two more days. Depending on the size of the final

From bioreactor

First extractor

/filter 11 r

Solvent = purification column

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