Optimizing fermentation processes

Damascene, L.M., Pla, I., Chang, H.J., Cohen, L., Ritter, G. et al. (2004) An optimized fermentation process for high-level production of a single-chain... 

With the very strong incentive to produce microbial products as cheaply as possible, considerable efforts have gone into identifying cheap feedstocks and into optimizing fermentation processes. From a consideration of the yields of microbial oils (section 9.2), it can be appreciated that a minimum of 5 tonnes of substrate (or feedstock) are needed to produce 1 tonne of oil under optimal fermentation conditions. Very often the lipid yield will be less than this 20% thus necessitating an even higher outlay for the purchase of the carbon source. 

Fermentation. Much time and effort has been spent in undertaking to find fermentation processes for vitamin C (47). One such approach is now practiced on an industrial scale, primarily in China. It is not certain, however, whether these processes will ultimately supplant the optimized Reichstein synthesis. One important problem is the instabiUty of ascorbic acid in water in the presence of oxygen it is thus highly unlikely that direct fermentation to ascorbic acid will be economically viable. The successful approaches to date involve fermentative preparation of an intermediate, which is then converted chemically to ascorbic acid. 

Traditionally, the upstream fermentation and cell culture processes have been viewed as being distinct from the subsequent downstream processing and purification steps, and the two different sets of processes nave been optimized individually. In some instances, careful consideration of the conditions used in the fermentation process, or manipulation of the genetic makeup of the host, can simplify and even... 

Most cells grow well under a fermentation process at a pH of around 7.0-7.4. However, as cells grow, CO2 is produced. To maintain optimal growth, the media are often buffered with, for example, phosphate buffered saline. Cells go through different phases of growth (Fig. 10.6). The cell viability, density, and consumption of nutrients are constantly monitored (Fig. 10.7). 

Finally, ion chromatography is sometimes used for process applications, allowing for the tracking of the manufacturing process in order to optimize process variables and to allow for better control of process parameters. One example of this is the application of ion chromatography to the analysis of fermentation broths. Here ion chromatography is used both to measure the level of ionic nutrients in the fermentation broth in order to control the fermentation process and also to measure the level of fermentation by-product ions which may be indicative of problems with the fermentation process. 

J.F. van Impe and G. Bastin. Advanced Instrumentation, Data Interpretation, and Control of Biotechnological Processes, chapter Optimal Adaptive Control of Fed-Batch Fermentation Process, pages 401-435. Kluwer Academic Publishers,... 

It has been shown that radio frequency impedance (RFI) is an effective tool for moifitoring cell density and cell growth of bioprocesses. The fermentation process, quite complex, is oftentimes difficult to sample and monitor. The RFI measurement could detect cell viability of Escherichia coli during the fermentation, serving as a qualitative measure of the metabolic load of the cell, and thus provide an in situ indicator of the optimal harvesting times. 

Overproduction must be achieved in the laboratory before pilot plant scale-up is attempted. Thus, following the successfiil laboratory development of improved strains, a mastery of the fermentation process for each new strain, as well as sound engineering know-how for media optimization and the fine-tuning of process conditions are required to yield integrated and... 

Han L, Parekh S. (2004) Development of improved strains and optimization of fermentation processes. In Barredo JL (ed). Microbial Processes and Products, (Humana, Totowa, New Jersey), pp. 1-23. 

The production of (-R)-PAC by fermenting yeast was one of the first industrially applied biotransformations, which is used to nowadays to obtain (R)-PAC as a chiral pre-step for L-ephedrine 2 [6-9] (Scheme 1), and the optimization of the fermentation process is still a matter of research [10 23],... 

Figure 5 Improvement ofECB bioconversion process due to improvements in the yields of the ECB and ECB deacylase fermentation processes and optimization of the bioconversion process itself.

The development of a commercially viable enzyme process for the production of ECB nucleus was achieved by improving the ECB and ECB deacylase fermentation processes and the bioconversion processes. Increased yields in the fermentation processes were achieved through linked programs for strain improvement and fermentation development. The bioconversion process was improved by the choice of substrate and enzyme conditions and subsequent optimization of operating conditions. An economic model was used to decide where development resources should be focused. 

Evaluation of Optimization Techniques for an Extractive Alcoholic Fermentation Process... 

The use of recombinant microorganisms for cofermentation is one of the most promising approaches in the field of bioethanol production, though their use for large-scale industrial processes still requires fine-tuning of the reliability of the entire process (2). The technical hurdles of cofermentation increase when real biomass hydrolysates have to be fermented. In fact, whatever the biomass pretreatment, the formation of degradation byproducts that could inhibit the fermentation usually requires the addition of a further detoxification step. Therefore, the production of ethanol from hydrolysates should be considered in its entirety, from the optimal pretreatment to the choice of the proper fermentation process. 

We explored the influence of dilution rate and pH in continuous cultures of Clostridium acetobutylicum. A 200-mL fibrous bed bioreactor was used to produce high cell density and butyrate concentrations at pH 5.4 and 35°C. By feeding glucose and butyrate as a cosubstrate, the fermentation was maintained in the solventogenesis phase, and the optimal butanol productivity of 4.6 g/(L h) and a yield of 0.42 g/g were obtained at a dilution rate of 0.9 h1 and pH 4.3. Compared to the conventional acetone-butanol-ethanol fermentation, the new fermentation process greatly improved butanol yield, making butanol production from corn an attractive alternative to ethanol fermentation. 

Optimizing the ABE fermentation process has long been the aspiration of more than a century of research. Conventionally, the profitability of fermentation is influenced by the type and concentration of substrate, dilution rate, pH, culture medium, and product recovery. Even using cell recycle, cell immobilization, or extractive fermentation to increase cell density and productivity, the yield of the combined ABE production never exceeded 0.44 g/g (13-15). 

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