Fermentation recovery process

J. West and A. Patterson, Whole Broth Extraction. Engineering foundation Conferences - Advances in Fermentation Recovery Process Technology, 1981. 

Drioli.E. Serafin.G. Rigoli,A. presented at First Engineering Foundation Conference " Advances in Fermentation Recovery Process Tech." Banff June 6-12 (1981) unpublished results. 

B. R. Smith, Oigank Acid Recoveiy with C pled-Tianspoit Membranes, paper presented at the Engineering Foundation Conference on Advances in fermentation Recovery Process Technology. Banff, Alberta. Canada, June 1981. See also Annual Reports for 1980 and subserpient,... 

Some of the economic hurdles and process cost centers of this conventional carbohydrate fermentation process, schematically shown in Eigure 1, are in the complex separation steps which are needed to recover and purify the product from the cmde fermentation broths. Eurthermore, approximately a ton of gypsum, CaSO, by-product is produced and needs to be disposed of for every ton of lactic acid produced by the conventional fermentation and recovery process (30). These factors have made large-scale production by this conventional route economically and ecologically unattractive. 

Methods of Purification. Although carbon dioxide produced and recovered by the methods outlined above has a high purity, it may contain traces of hydrogen sulfide and sulfur dioxide, which cause a slight odor or taste. The fermentation gas recovery processes include a purification stage, but carbon dioxide recovered by other methods must be further purified before it is acceptable for beverage, dry ice, or other uses. The most commonly used purification methods are treatments with potassium permanganate, potassium dichromate, or active carbon. 

The precipitated chromic hydroxide and sulfur are discarded. This process is used to purify carbon dioxide from fermentation ia the Reich process and as a final cleanup after the alkaU carbonate or ethanolamine recovery processes (22,23). 

By-Products. The biomass from the fungal fermentation process is called mycellium and can be used as a supplement for animal feed since it contains digestable nutrients (25,26). The lime-sulfuric purification and recovery process results in large quantities of calcium sulfate cake, which is usually disposed of into a landfill but can find limited use in making plaster, cement, waUboard, or as an agricultural soil conditioner. The Hquid extraction purification and recovery process has the advantage of Htde soHd by-products. 

Several factors affect the overall economics of PHA production. These include PHA productivity, PHA content, yield of PHA on carbon source, carbon substrate cost, and recovery method employed. Figure 1 shows the production costs of P(3HB) by various P(3HB) contents and P(3HB) productivities [29]. The effect of P(3HB) productivity on the production cost is only related to the cost of the fermentation equipment [18]. However, the P(3HB) content has multiple effects on the volume of the fermentation equipment and the recovery process [17,18]. The increase of P(3HB) yield on carbon source and the use of less expensive carbon substrates reduce the cost of carbon substrate [17, 29]. Development of an efficient recovery method, which will be different for each bacterium employed, is also important to overall economics of PHA production. When the actual fermentation processes employing many different re-... 

These new fermentation processes often require high costs for recovering the product from the fermentation broth. For instance, the production of lactic acid requires the neutralization of the product during the fermentation, to avoid acidification of the medium, and the subsequent re-acidification of the lactate [65]. Similarly, the recovery of 1-butanol implies the distillation of large amounts of water. Alternative recovery processes are therefore the subject of intensive research. 

Recognizing the need for a more economically and environmentally friendly citric acid recovery process, an adsorptive separation process to recover citric acid from fermentation broth was developed by UOP [9-14] using resin adsorbents. No waste gypsum is generated with the adsorption technique. The citric acid product recovered from the Sorbex pilot plant either met or exceeded all specifications, including that for readily carbonizable substances. An analysis of the citric acid product generated from a commercially prepared fermentation broth is shown in Table 6.2, along with typical production specifications. The example sited here is not related to zeolite separation. It is intent to demonstrate the impact of adsorption to other separation processes. 

In order to develop a host strain for production of a variety of subtilisin enzymes, it was first necessary to delete the endogenous alkaline and neutral proteases (72,76). The strain was then constmcted to contain the optimal combination of subtilisin regulatory genes which were compatible with the proposed fermentation and recovery process. Once this strain had been produced, the recombinant enzyme... 

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). 

Like APIs, pharmaceutical excipients are made by chemical synthesis, fermentation, recovery from natural materials, and so on. Often purification procedures may not be employed in the manufacture of such pharmaceutical excipients as clays, celluloses, starches, and natural gums. In addition, the physical and chemical change of certain excipients during processing is not uncommon. Unlike APIs, many excipients have complicated chemical and physical structures that do not yield easily to modern analytical and chromatographic methods. 

The isolation and purification of fermentation products is often collectively referred to as downstream processing. The early part of the separation of a bioproduct is the primary recovery process, whereas the elements further downstream may include purification, concentration, and formulation. The overall goal of downstream processing and formulation is to recover the product of interest cost effectively at high yield, purity, and concentration, and in a form that is stable, safe, and easy to use in a target application. 

Reverse micelles are self-organized aggregates of amphiphilic molecules that provide a hydrophilic nano-scale droplet in apolar solvents. This polar core accommodates some hydrophilic biomolecules stabilized by a surfactant shell layer. Furthermore, reverse micellar solutions can extract proteins from aqueous bulk solutions through a water-oil interface. Such a liquid-liquid extraction technique is easy to scale up without a loss in resolution capability, complex equipment design, economic limitations and the impossibility of a continuous mode of operation. Therefore, reverse micellar protein extraction has great potential in facilitating large-scale protein recovery processes from fermentation broths for effective protein production. 

We are indebted to technical help from microbial fermentation and recovery process development groups at Amgen Inc. in the expression and isolation of rhSCF. 

The final concentration of the fermentation product is usually low (less than 0.2 wt%). Therefore, new processing techniques must be developed to improve the existing biochemical product recovery procedures. The conventional biochemical product recovery processes can be divided into four sections 1. Removal of insolubles 2. Primary isolation of product 3. Purification... 

The fermentation department can consume up to 2/3 of the total plant electrical requirements (depending upon the recovery process), which includes mechanical agitation (usually 15 hp/1000 gal) and electrically driven air compressors. 

These chelating resins have found most of their use in metal ion recovery processes in the chemical and waste recovery industries. They may find use in fermentation applications where the cultured organism requires the use of metal ion cofactors. Specific ion exchange resins have also been used in laboratory applications that may find eventual use in biotechnology product recovery applications. 

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