Cephalosporin purification from fermentation

Approaches to Cephalosporin C Purification from Fermentation Broth... 

Wildfeuer, M. E. (1985) Approaches to Cephalosporin C purification from fermentation broth, in Purification of Fermentation Products (Le Roith, D., Shiloach,... 

Figure 12.18 Purification of cephalosporin C from a fermentation broth. (Left) Analysis. Same experimental conditions as in displacement. (Right) Displacement. Column 350 x 4.6 mm, packed with 5 im Zorbax carrier 1% v/v acetonitrile in 20 mM sodium acetate pH 5.2 displacer 40 mg/mL BEE in carrier feed 5 mL fermentation broth flow rate 1.0 mL/min fraction volume 300 jiL. Reproduced with permission from G. Subramanian, M. Phillips and S. Cramer,. Chromatogr., 439 (1988) 341 (Fig. 5).

Solvent extraction is widely used during early purification of fermentation-derived products and, indeed, of all natural product matrices for initial and intermediate purification prior to final purification by chromatography, crystallization, or precipitation. Solvent extraction provides the ease of liquid handling, the potential for high-throughput operation, and the potential for adaptation to continuous operation. Both water-miscible and immiscible solvents are used for extracting compoimds from the biomass. Frequently, multiple approaches can be employed to purify a fermentation-derived product. Wildfeuer (11) describes many possible approaches for purification of the antibiotic cephalosporin C. 

Adding up the times of all steps, an industrial scale production takes roughly 3 weeks, of which 2 weeks are devoted to the fermentation and about 1 week is required for the downstream processing. Derivatization at positions 3 and 7 to yield an API is not included. Starting from 7-ACA, these processes may take 1 day each for the derivatization plus the time for purification, crystallization, and drying. The resulting bulk active cephalosporin can then be sterilized and formulated for marketing. 

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