Tub extraction and purification of fermentation products may be difficult and costly. Ideally, one is trying to obtain a high-quality product as quickly as possible at an efficient recovery rate using minimum plant investment operated at minimal costs. Unfortunately, recovery costs of microbial products may vary from as low as 15% to as high as 70% of the total manufacturing costs (Aiba et al, 1973; Swartz, 1979; Pace and Smith, 1981; Atkinson and Sainter, 1982; Datar, 1986). Obviously, the chosen process, and therefore its relative cost, will depend on the specific product. Atkinson and Mavituna (1991) indicate percentage of total costs being 15% for industrial ethanol, 20-30% for bulk penicillin G and up to 70% for enzymes. The high (and sometimes dominant) cost of downstream processing will affect the overall objective in some fermentations.

If a fermentation broth is analysed at the time of harvesting it will be discovered that the specific product may be present at a low concentration in an aqueous solution that contains intact micro-organisms, cell fragments, soluble and insoluble medium components and other metabolic products. The product may also be intracellular, heat labile and easily broken down by contaminating micro-organisms. All these factors tend to increase the difficulties of product recovery. To ensure good recovery or purification, speed of operation may be the overriding factor because of the labile nature of a product. The processing equipment must therefore be of the correct type and also the correct size to ensure that the harvested broth can be processed within a satisfactory time limit.

The choice of recovery process is based on the following criteria:

1. The intracellular or extracellular location of the product.

2. The concentration of the product in the fermentation broth.

3. The physical and chemical properties of the desired product (as an aid to selecting separation procedures).

4. The intended use of the product.

5. The minimal acceptable standard of purity.

6. The magnitude of bio-hazard of the product or broth.

7. The impurities in the fermenter broth.

8. The marketable price for the product.

The main objective of the first stage for the recovery of an extracellular product is the removal of large solid particles and microbial cells usually by centrifugation or filtration (Fig. 10.1). In the next stage, the broth is fractionated or extracted into major fractions using ultrafiltration, reverse osmosis, adsorption/ion-exchange/gel filtration or affinity chromatography, liquid-liquid extraction, two phase aqueous extraction or precipitation. Afterwards, the product-containing fraction is purified by fractional precipitation, further more precise chromatographic techniques and crystallization to obtain a product which is highly concentrated and essentially free from impurities. Other products are isolated using modifications of this flow-stream.

Attempts to simplify this outline extraction procedure for antibiotic recovery using 'whole broth' processing have met with limited success. The technique of

Fermentation Broth

Removal of solids

Removal of solids

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