Fermentation processes penicillin recovery

Occurrence, Fermentation, and Biosynthesis. Although a large number of Streptomjces species have been shown to produce carbapenems, only S. cattkja (2) and S. penemfaciens (11) have been reported to give thienamycin (2). Generally the antibiotics occur as a mixture of analogues or isomers and are often co-produced with penicillin N and cephamycin C. Yields are low compared to other P-lactams produced by streptomycetes, and titres are of the order of 1—20 p-g sohdusmL despite, in many cases, a great deal of effort on the optimization of the media and fermentation conditions. The rather poor stabiUty of the compounds also contributes to a low recovery in the isolation procedures. The fermentation and isolation processes for thienamycin and the olivanic acids has been reviewed in some detail (12). 

The fermentation step to produce penicillin GA is the major cost element in the overall process to produce 6-APA. This is substantially due to the high cost of sterile engineering (Table 4.6 and 4.7). Clarification, extraction and solvent recovery steps are also significant, a reflection of the dilute and impure composition of fermentation broths. The concentration of 6-APA in the final broth has a big effect on total process costs. Thus increasing final 6-APA concentrations from 1.2-6.0% have been calculated to reduce production costs by over 50% (Table 4.8). By contrast the 6-APA production step cost is quite small, and is less that half the cost of the solvent recovery process (Table 4.6). The costs of the immobilized enzyme is not insignificant in a recent calculation it was estimated at 2.5 /kg 6-APA (Rasor and Tischer, 1998). 

Biochemical Processing. Potential ELM applications in biochemical processing (44) include the separation of aminoacids (L-phenylalanine), biochemicals (acrylic and propionic acids), and antibiotics (penicillin G) from fermentation broths. A typical ELM system for the recovery of L>phenylalanine from fermentation broths is given in Table DC (45,46). The recovery from a broth containing 12-35 g/L of L-phenylalanine can be about 80% with a single batch extraction. Hong et al. (45) obtained a recovery of about 99% with four serial batch extractions in simulating their proposed continuous process with mixer-settler extractors. 

Solvent recovery by extraction While most processes use distillation or evaporation to recover the solvent from the product solutions of liquid extraction, it is not uncommon to recover solvent by liquid extraction. A typical example is the recovery of penicillin from the acidified fermentation broth in which it occurs by extraction with amyl acetate as solvent, followed by stripping of the penicillin from the solvent by extracting it into an aqueous buffer solution. The amyl acetate is then returned to the first extraction. The calculations of such solvent-recovery operations are made in the same manner as those for the first extraction. 

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