Temperature penicillin fermentation

Example 5.5 Optimal Temperature Profile for Penicillin Fermentation... 

Example 5.5 Solution of the Optimal Temperature Profile for Penicillin Fermentation. Apply the orthogonal collocation method to solve the two-point boundary-value problem arising from the application of the maximum principle ofPontryagin to a batch penicillin fermentation. Obtain the solution of this problem, and show the profdes of the state variables, the adjoint variables, and the optimal temperature. The equations that describe the state of the system in a batch penicillin fermentation, developed by Constantinides et al.(6], are ... 

Figs. E5.5a to E5.5d show the profiles of the system variables and the optimal control variable (temperature). For this particular formulation of the penicillin fermentation, the maximum principle indicates that the optimal temperature profile varies from 30 to 20°C in the pattern shown in Fig. E5.5c/. 

Processes, II. Optimum Temperature Profiles for Batch Penicillin Fermentations. Biotech. Bioeng., vol. 12. 1970, p. 1081. 

World War II spurred much advancement in the production of penicillin, particularly the advent of submerged fermentation processes. This new technique was soon adapted to the large-scale production of bacterial proteases. The first modern detergent protease, isolated from Bacillus licheniformis, was introduced in 1962. This enzyme, a particular type of protease called a subtilase, was stable at higher temperatures, had broad substrate specificity and worked well in alkaline conditions. The appearance of this enzyme and others similar to it (i.e., subtilisins) opened up the detergent enzymes market, and by 1969, 50% of the laundry detergent products sold in the United States and Europe contained enzymes. ... 

Penicillin V could be measured during the entire fermentation run with the same enzyme column without serious problems in spite of rapid temperature variations between 20 and 40 °C, high humidity, and vibrations. The linear... 

When separation by distillation is ineffective or very difficult, liquid extraction is one of the main alternatives to consider. Qose-boiling mixtures or substances that caimot withstand the temperature of distillation, even under a vacuiun, may often be separated from impurities by extraction, which utilizes chemical differences instead of vapor-pressure differences. For example, penidliin is recovered from the fermentation broth by extraction with a solvent such as butyl acetate, after lowering the pH to get a favorable partition coefficient. The solvent is then treated with a buffered phosphate solution to extract the penicillin from the solvent and give a purified aqueous solution, from which penicillin is eventually produced by drying. Extraction is also used to recover acetic acid from dilute aqueous solutions distillation would be possible in this case, but the extraction step considerably reduces the amount of water to be distilled. 

Partition coefficients of solutes are influenced by aqueous-solution properties (pH, ionic strength) and the solvent (hydrophobicity, polarity). Partition coefficients are relatively insensitive to temperature or solute concentrations over the ranges normally used in fermentation-broth processing. Among the aqueous properties, the pH is one of the more important variables (particularly for weak bases and acids). Several primary and secondary metabolites, such as penicillin, are weak acids or bases, and the pH can be used to control and even reverse the distribution coefficient. A list of pharmaceutical products that are weak acids or bases and are extracted with solvent is given in Table 4. 

An aqueous dilute fermentation broth contains 0.5 wt% of penicillin F. It is to be extracted with amyl acetate. At room temperature and pH = 3.2 water and amyl acetate are esentially insoluble, and the distribution coefficient for the penicillin is m = 80. 

On the othw hand, Owen and Johnson (1955) have reported on the effect of temperature changes on the production of penicillin, and it was found that 50% more penicillin was produced by fermentations started... 

Inorganic membranes, usually appUed when high temperatures or chemically active mixtures are involved, are made of ceramics [171,172], zirconia-coated graphite [173],silica-zirconia [174],zeolites [168], or porous glass [175] among others [176]. Ceramic membranes are steam sterilizable and offer a higher mechanical stability [134], thus they may be preferably used in aseptic fermentations, since some hollow fibers are only chemically sterilizable and not very suitable for reuse. Composite materials, in which glass fiber filters are used as support for the polymerization of acrylamide monomers, were developed for the hydrolysis of penicillin G in an electrically immobilized enzyme reactor. By careful adjustment of the isoelectric point of amphoteric membranes, the product of interest (6-aminopenicillanic acid) was retained in an adequate chamber, adjacent to the reaction chamber, while the main contaminant (phenyl acetic acid), was collected in a third chamber [120]. 

With the development in the fermentation broth of concentrations of the order of 500 O.U./cu. cm. total penicillin (80 per cent penicillin-G), the concentration procedures have not required adsorption on activated carbon (158). A presently recommended flowsheet (89) involves continuous, countercurrent, multistage extraction of the filtered and acidified (pH 2 to 2.15) broth with a one-fifth volume of amyl acetate in the centrifugal extractor at room temperature similar extraction into a volume of cold buffer solution (pH 6.8 to 7.0) acidification to pH 2 and reextraction into a K... 

Aminopenicillinic acid (6-APA) is made from Penicillin G. The current fermentation approach gives a relatively pure aqueous solution containing a high concentration of Penicillin G. Solvent extraction is used to recover the product. However, ion exchange resins could be used to recover the product as well. The chemical method involves a very low temperature operation ( 40°G) and the use of several solvents (see Fig. 9.12). The waste stream will contain chlorinated solvents and organics. The biotechnology process is operated at room temperature and does not produce waste. The immobilization of the enzyme is still a research area. 

The maximum principle has been applied to the above model to determine the optimal temperature profile (see Ref. [7]), which maximizes the concentration of penicillin at the final time of the fermentation, tf-. The maximum principle algorithm when applied to the state equations, (1) and (2), yields the following additional equations ... 

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