Fed-batch fermentors

Bakers Yeast Production. Bakers yeast is grown aerobicaHy in fed-batch fermentors under conditions of carbohydrate limitation. This maximizes the yield of yeast biomass and minimizes the production of ethanol. Yeasts grown under these conditions have exceUent dough leavening capabHity and perform much better in the bakery than yeast grown under anaerobic conditions. 

For the detailed discussion on the inductive learning of diagnostic and control rules around the fed-batch fermentor system, the reader should refer to the work of Bakshi and Stephanopoulos (1994b). 

Tragardh, Ch., A Hydrodynamic Model for the Simulation of an Aerated Agitated Fed-Batch Fermentor . Proceedings of the 2nd International Conference on Bioreactor Fluid Dynamics, Cambridge, UK 117-134 (1988). 

Luus, R. Optimization of Fed-batch Fermentors by Iterative Dynamic Programming. Biotechnol Bioeng 41 599-602 (1992). 

Suppose that a well-mixed stirred tank is being used as a fed-batch fermentor at a constant feed rate F (m h ), substrate concentration in the feed C j (kg m ), and at a dilution rate D equal to the specific cell growth rate p. Ihe cell concentration Cjj (kgrn ) and the substrate concentration (kgm ) in the fermentor do not... 

The substrate concentration in a fed-batch fermentor can be maintained nearly constant, as shown in previous works (9), and in this case one can assume that dS/dt 0, and from Eq. 1... 

Intermediates in the biosynthetic route are 3-dehydroshikimic acid, protocate-chuic acid and catechol (Scheme 7.16). Optimization of microbial ds,ds-muconic acid synthesis required the expression of three enzymes not typically found in Escherichia coli [42cj. E. coli WNl/pWN2.248 was developed that synthesized 36.8 g of ds,ds-muconic acid in a 22% (mol/mol) yield from glucose after 48 h of culturing under fed-batch fermentor conditions. Optimization of the carbon flow directed into ds,ds-muconic acid biosynthesis and manipulation of enzyme activities were aimed at avoiding accumulation of biosynthetic intermediates. 

ABE production was studied by Qureshi et al [3.91] in a laboratory PVMBR system, which coupled a fed-batch fermentor (using C. acetobutylicum) with an UF membrane and a PV product recovery system using a silicalite-silicone composite membrane. Cells of C. acetobutylicum were removed from the culture using the 500,000 molecular weight... 

A comparison between the model and an experimental laboratory batch fermentor as well as an industrial fed-batch fermentor is also presented to the reader. The model is shown to simulate reasonably well the experimental results, with the largest deviation being for the concentration of yeast. 

Consider a simple isothermal fed-batch fermenter with a single bio-reaction where biomass (with concentration X) is produced using some substrate (with concentration 5). Assume that only substrate is fed into the reactor with concentration Sp. If constant physico-chemical properties and the presence of an inert solvent are assumed then the lumped dynamic model of a simple fed-batch fermentor is as follows ... 

Park et al. [251, 252] used a mutant strain of R. eutropha capable of using alcohols as a carbon source for the production of PHB and PHBV in fed-batch fermentors. With phosphate limitation as inducing factor, ethanol was used for the production in 7 L of 46.6 g PHB L (74% of the CDM) in 50 h [251]. When 1-propanol was added to the medium, up to 15.1 mol% in 3HV units were incorporated to the polymer, and when propanol was the sole carbon source, the cells accumulated about 85% of their CDM in P(3HB-co-35.2-mol% 3HV). Both alcohols were completely consumed. In computer-controlled fermentations [252], switches between the alcohols or mixtures thereof led to improved copolymer yield from the substrates and production rates. 

Commercial-scale operations are conducted in batch, fed-batch, or continuous culture systems. Fermentation vessels include the conventional baffled aerated tank, with or without impeller agitation, and the ak-lift tower fermentors in which ak is sparged into an annular space between the... 

S. cerevisiae is produced by fed-batch processes in which molasses supplemented with sources of nitrogen and phosphoms, such as ammonia, ammonium sulfate, ammonium phosphate, and phosphoric acid, are fed incrementally to meet nutritional requirements of the yeast during growth. Large (150 to 300 m ) total volume aerated fermentors provided with internal coils for cooling water are employed in these processes (5). Substrates and nutrients ate sterilized in a heat exchanger and then fed to a cleaned—sanitized fermentor to minimize contamination problems. 

C. uti/is yeast is produced by either fed-batch or continuous processes. Aerated-agitated fermentors range up to 300 m total capacity and ate operated in the same manner as described for S. cerevisiae (2,5). C. utilis is capable of metabolizing both hexose and pentose sugars. Consequendy, papermiU wastes such as sulfite waste Hquot that contain these sugars often ate used as substrates. 

The batch and fed-batch procedures are used for most commercial antibiotic fermentations. A typical batch fermentor may hold over 150,000 Hters. When a maximum yield of antibiotic is obtained, the fermentation broth is processed by purification procedures tailored for the specific antibiotic being produced. Nonpolar antibiotics are usually purified by solvent extraction procedures water-soluble compounds are commonly purified by ion-exchange methods. Chromatography procedures can readily provide high quaHty material, but for economic reasons chromatography steps are avoided if possible. 

Fed-batch fermentation process is a production technique between batch and continuous fermentation. A proper medium feed rate is required to add sequentially into the fermentor during the process and the product is harvested at the end of fermentation just like a batch type. 

Fig. 6 shows a fed batch fermentation of sweet sorghum juice (SSJ) by Bacillus aryabhattai in 3 L fermentor under cultivating condition with agitation rate at 200 rpm, air rate of 1.5 1/min, at 30° C and feeding time at 18 and 24 hr during log phase of the culture. It was found that the cell could continuously produce both biomass and PHAs. Maximum cells were obtained at about 14.20 g/1 at 54 hr when PHAs content reached 4.84 g/1 after 66 hr (Tanamool et al., 2011). In addition, in Table 2, fed batch fermentation by A, latus was used for the production of PHAs (Yamane et al, 1996 Wang Lee, 1997). It could yield high productivity with the use of cheap carbon sources. 

Fig. 6. Growth monitoring and PHAs production during fed-batch fermentation of sweet sorghum by Bacillus arybhattai in 3 L fermentor (Tanamool et al., 2011)...

Bakshi and Stephanopoulos (1994b) have applied the above procedure to a fed-batch fermentation process. The problem involved 41 sets of batch records on 24 measured variables. Of these variables only very few were found by the decision tree to be relevant, and yield rules such as the following for guiding the diagnosis or control of a fermentor. 

In the fed-batch operation of fermentors (which is also commonly practiced), the feed is added either continuously or intermittently to the fermentor, without any product withdrawal, the aim being to avoid any excessive fluctuations of oxygen demand, substrate consumption, and other variable operating conditions. 

In a fed-batch culture (semi-batch culture, see Figure 7.1b), a fresh medium that contains a substrate but no cells is fed to the fermentor, without product removal. The fed-batch operation has special importance in biotechnology, as it is the most... 

Thus, if D is made equal to fi, the cell concentration would not vary with time. For a given substrate concentration in the fermentor C, fi is given by the Monod equation (i.e.. Equation 4.6). Alternatively, we can adjust the substrate concentration Cj for a given value of fi. Practical operation usually starts as batch culture and, when an appropriate cell concentration is reached, the operation is switched to a fed-batch culture. 

Fed-batch culture is not a steady-state process, as the liquid volume in the fermentor increases with time and withdrawal of products is not continuous. However, the feed rate and the concentrations of cells and substrate in the broth in a fermentor can be made steady. 

The characteristics of the fed-batch culture, shown by Equations 12.21 and 12.23, make it possible to keep the concentrations of the substrate and/or the cell at the desired values. For example, after a batch culture, a feed medium that contains the substrate at a high concentration can be fed, either continuously or intermittently, to the fermentor under a fed-batch operation. The values of the dilution rate and the substrate concentration in the feed medium can be determined using Equation 12.23. Thus, by using the fed-batch operation, the yield and/or productivity can be greatly improved in a variety of areas of biotechnology by controlling the concentrations of substrate and cell. Some examples of where the fed-batch operation can be effectively used are as follows. 

Bioreactors that use enzymes but not microbial cells could be regarded as fermentors in the broadest sense. Although their modes of operation are similar to those of microbial fermentors, fed-batch operation is seldom practiced for enzyme reactors. The basic equations for batch and continuous reactors for... 

Commercial fermentations are conducted in large bioreactors which are usually referred to as fermentors and arc designed tor operation in batch, fed-baldi. or continuous ferine illation modes. The batch and fed-batch procedures are used for most commercial antibiotic fermentations. 

One of the most important biochemical reactors is the fermentor. We provided a simple example of a batch fermentor in Chapter 4. But there are many other types including continuous, batch, and fed-batch. There are some other useful references in the literature.16-17... 

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