Fermentation development scale

Besides wastewater treatment, pervaporation systems have also been tested on a development scale for continually removing volatile organic products (e.g., ethanol, volatile acids) from fermentation broths. 

The final process fermentation development standardised parameters such as temperature exposure, operating parameters, cleaning and passivation to overcome the corrosive effect of saline fermentation and was performed in 500-1500 L industrial-scale stainless steel fermenters. This, together with careful design of the timing and method for introducing the resin to the production fermenter, resulted in production titres of 250-300 mg/L in 500-1500 L industrial fermenters. 

Biochemical impurities originate from the media components, antifoams, oils, and metal ions, and may include metabolites closely related to the compound of interest they can all affect empirical isolation procedures. It is therefore essential to maintain close liaison between the fermentation and extraction scientists during all aspects of scale-up to ensure that fermentation developments are not adversely affecting isolation procedures. The inevitably changing nature of the feedstock further highlights the requirement for a quantitative specific assay for the product and an assessment of product purity throughout the isolation process. 

Sniff K S, Garcia L A, Hassler R A, et al. (1996). Process development, scale-up and validation of a recombinant E. co/i-based fermentation process. ASTM Spec. Tech. Publ., STP 1260 97-106. 

The more analytical tools that are available and the better the understanding of critical biochemical pathways, the more rapidly fermentation processes can be developed. Besides those previously mentioned, a munber of different parameters have been monitored on-line in fermentation development [7], including exhaust gas analysis and gas fluxes [46], cell density [47], redox potential [48], IR [49], culture fluorescence [50], biological activities [45 ], and viscosity. It is important to iterate that small-scale fermentation studies should aim to develop relatively simple control systems that are easily scaled. As an example, although HPLC systems are routinely set-up on line to measure and control laboratory scale fermentations, the robustness of such a system and its utility in a manufacturing facility remains debatable. 

Scale-down studies are a valuable tool in fermentation development [51]. If production is going to occur in a fermentor for which the KLa or other parameter is precisely defined [52], correct down-scaled reactors should be used to mimic such configurations. Scale-down studies are helpful in that restrictions due to scale up are known in advance, thus minimizing small-scale studies that do not satisfy the ultimate good. 

Kossen and Oosterhuis (1985) proposed two ways to solve the problem of scale-up of bioreactors first, by acquiring more knowledge about the hydrodynamics and interaction of the hydrodynamics with other mechanisms in production scale fermenters, and second, by developing scale-up procedures that give an adequate estimation of the performance of production scale fermenters based on small scale investigations. This approach is discussed in detail in later sections. 

Large-scale penicillin fermentation developed in the United States 1950s Bioconversion of steroid hormones at Up>john and Schering 1956 Fermentation process for L-glutamic acid developed... 

Until World War 1 acetone was manufactured commercially by the dry distillation of calcium acetate from lime and pyroligneous acid (wood distillate) (9). During the war processes for acetic acid from acetylene and by fermentation supplanted the pyroligneous acid (10). In turn these methods were displaced by the process developed for the bacterial fermentation of carbohydrates (cornstarch and molasses) to acetone and alcohols (11). At one time Pubhcker Industries, Commercial Solvents, and National Distillers had combined biofermentation capacity of 22,700 metric tons of acetone per year. Biofermentation became noncompetitive around 1960 because of the economics of scale of the isopropyl alcohol dehydrogenation and cumene hydroperoxide processes. 

The modem fermentation industries developed from the early era of antibiotics. Over 4000 antibiotics have been discovered since the 1950s. However, only about 100 are produced on a commercial scale and over 40 of these are prepared by a combination of microbial synthesis and chemical modifications. Antibiotics produced by fermentation and used as starting materials in chemical syntheses are given in Table 2. 

L-Sorhose to 2-KGA Fermentation. In China, a variant of the Reichstein-Grbssner synthesis has been developed on an industrial scale (see Fig. 5). L-Sorbose is oxidized direcdy to 2-ketogulonic acid (2-KGA) (24) in a mixed culture fermentation step (48). Acid-catalyzed lactonization and enolization of 2-KGA produces L-ascorbic acid (1). 

Fermentative Manufacture. Throughout the years, riboflavin yields obtained by fermentation have been improved to the point of commercial feasibiUty. Most of the riboflavin thus produced is consumed in the form of cmde concentrates for the enrichment of animal feeds. Riboflavin was first produced by fermentation in 1940 from the residue of butanol—acetone fermentation. Several methods were developed for large-scale production (41). A suitable carbohydrate-containing mash is prepared and sterilised, and the pH adjusted to 6—7. The mash is buffered with calcium carbonate, inoculated with Clostridium acetohutylicum and incubated at 37—40°C for 2—3 d. The yield is ca 70 mg riboflavin/L (42) (see Fermentation). 

Scale-Up Fermenters ranging from about two to over 100 hters (0.07-3.5 fP) have been used for research and development, but the smaller sizes provide too httle volume for sampling and are difficult to replicate, whue large vessels are expensive and use too much medium. Autoclavable small fermenters that are placed in a water bath for temperature control are less expensive than vessels with jackets or coils, but much labor is required for handling them. Pressure vessels that... 

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