10. Further processing of penicillin salt

Fig. 10.2. Recovery and partial purification of penicillin G.

'whole broth' processing involves initial removal of large particles, which is then followed by passage of the broth (including cells) through, for example, well mixed ion-exchange columns or counter-current liquid-liquid extraction units to extract the product directly. This topic will be discussed in more detail in a later section of this chapter.

It may be possible to modify the handling character istics of the broth so that it can be handled faster with simpler equipment making use of a number of techniques:

1. Selection of a micro-organism which does not produce pigments or undesirable metabolites.

2. Modification of the fermentation conditions to reduce the production of undesirable metabolites.

3. Precise timing of harvesting.

4. pH control after harvesting.

5. Temperature treatment after harvesting.

6. Addition of flocculating agents.

7. Use of enzymes to attack cell walls.

It must be remembered that the fermentation and product recovery are integral parts of an overall process. Because of the interactions between the two, neitlvi stage should be developed independently, as this might result in problems and unnecessary expense. Dar-byshire (1981) has considered this problem with reference to enzyme recovery. The parameters to consider included time of harvest, pigment production, ionic strength and culture medium constituents. Large volumes of supernatants containing extracellular enzymes need immediate processing while harvesting times and enzyme yields might not be predictable. This can make recovery programmes difficult to plan. Pigment production might make some recovery procedures difficult, when the pigment binds to the same resin as the enzyme. Changes in fermentation conditions may reduce pigment formation. Certain antifoams remain in the supernatant and affect ultrafiltration or ion-exchange resins used in recovery stages. Trials may be needed to find the most suitable antifoam (see also Chapter 4). The ionic strength of the production medium may be too high, resulting in the harvested supernatant needing dilution with demineralized water before it can be processed. Such a negative procedure should be avoided if possible by unified research and development programmes. Media formulation is dominated by production requirements, but the protein content of complex media should be critically examined in view of subsequent enzyme recovery. This view is also shared by Topiwala and Khosrovi (1978), when considering water recycle in biomass production. They stated that the interaction between the different unit operations in a recycle process made it imperative that commercial plant design and operation should be viewed in an integrated fashion.

Flow sheets for recovery of penicillin, cephamycin C,

1. Fermenter broth containing cephamycin C

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