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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Company
    Nature biotechnology 2 (1984), S. 875-883 
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Many of the physical and chemical parameters which influence the behavior of a microorganism are changed as the scale of operation is changed. A description is given of how the most important of these effect process performance. As well as opening up new doors for novel process control techniques, ...
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 7 (1992), S. 257-263 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Experiments using a soluble, chemically defined fermentation medium provided important knowledge about the kinetics of efrotomycin biosynthesis. Equivalent titers were obtained in a batch process in both shaker flasks and fermentors. By extended feeding of both monosodium glutamate and glycerol at elevated temperatures, in combination with sulphuric acid pH control, the specific production rate was increased 2.8 fold and overall production rate was improved 5-fold. If the monosodium glutamate was fed too fast, then ammonium accumulated with indications of strong repression of efrotomycin biosynthesis at concentrations above 6 mM. In contrast to the complex medium used for this process, the chemically define medium was completely insensitive to changes in sterilization conditions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess engineering 19 (1998), S. 403-413 
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Radial flow Rushton impellers were compared qualitatively with axial flow hydrofoil impellers (Maxflo T and A315) at the pilot scale. Six types of impellers were compared for qualitative differences in mass transfer. Measurements were conducted using three model systems: water, glycerol and Melojel (soluble starch). Power measurements were obtained using watt transducers, which although limited in accuracy and prone to interferences, were able to provide useful qualitative monitoring results. While there was little effect of impeller type on mass transfer as measured by the rapid pressure increase technique, significant qualitative differences were observed using the rapid temperature increase technique specifically for the Melojel and glycerol model systems. The Miller correlation, relating gassed-to-ungassed power, was used effectively to qualitatively evaluate the power drop upon gassing for both the model systems and a Streptomyces fermentation for the various impeller types. A high oxygen demand Streptomcyes fermentation then was conducted in fermenters possessing each type of impeller. Performance was not adequate with the A315 impellers pumping upwards and the small diameter Maxflo T impellers. Peak titers and profiles of the estimated apparent broth viscosity varied depending upon the impeller type. Mass transfer rates generally declined with higher viscosities when other fermentation operating conditions where held constant. Overall, values for OUR, k L a, P g /V L and other calculated mass transfer and power input quantities for the A315 pumping upwards and undersized Maxflo T (D T /D I  = 2.3) impellers were at the lower end of the range obtained for the larger Maxflo T (D T /D I  = 1.8–2.0) and A315 impellers pumping downwards. Rushton impellers generally behaved qualitatively similar to hydrofoil impellers based on these calculated quantities.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess engineering 18 (1998), S. 401-412 
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Prior investigations comparing radial flow Rushton impellers with axial flow hydrofoil impellers (Maxflo T and A315) were extended at the pilot scale. Six types of impellers (disk-style Rushton, Prochem Maxflo T hydrofoils of three diameters pumping downwards and A315 hydrofoils pumping upwards and downwards) were compared for qualitative differences in power number behavior with Reynolds' number, single versus double impeller power draw, gassed power reduction with aeration number and gas hold-up. Power measurements were obtained using watt transducers which, although limited in accuracy and prone to interferences, were able to provide useful qualitative monitoring results. Measurements were conducted using three model liquid systems: water, glycerol and Melojel (soluble starch). Apparent viscosities for actual Streptomyces cultivations were estimated using measured gassed power values and the experimental relationships obtained for gassed/ungassed power to aeration number and power number to Reynolds' number for the glycerol model system. Results confirmed the lower power number and lower shear environment for hydrofoil impellers, yet suggested useful trends for various process parameters and process fluids.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Modified microbial fermenters were adapted for use in animal cell cultivations within an active microbial pilot plant rapidly and inexpensively. Multiple batches of Jurkat cells (human T-lymphoma) and Spodoptera frugiperda (using a baculovirus expression vector) were conducted in modified 75 L Chemap fermenters and a 280 L pilot plant seed vessel. These retrofitted reactors were evaluated for suitable temperature control, local hot spots, surface aeration capability, open-pipe sparging, impeller type and impeller speed. Influences of these operating factors on cell growth rate, cell density, glucose uptake and protein yield were quantified. Implications for the flexible design of fermenters for operation in multiuse campaign facilities are discussed. Adaption of existing microbial fermenters was found to be an attractive route for initial implementation of cell culture capacity in a research organization.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 3 (1988), S. 31-36 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A description is given of the application of computer process control and on-line data aquisition for the rapid scale-up of the Efrotomycin fermentation. This process involves the use of a pseudo-mycelial culture, solids and oil containing medium, and exhibits a high degree of sensitivity to small changes in sterilization conditions. The latter point presented the major scale-up challenge, especially when batch sterilization of medium was used. An example is given of how on-line computer-generated data were used to monitor overall metabolic changes and how this information was used to make process control decisions during the fermentation. The agitator speed was automatically controlled at the larger scale to maintain the required dissolved oxygen concentration and this enabled us to rapidly scale-up based on constant oxygen transfer coefficient. The necessary accuracy of control of sterilization conditions required at the various different scales of operation could only be met by use of continuous HTST (high temperature short time) sterilization of the medium. In addition, use of the continuous sterilizer made it much easier to specify conditions for different scales of operation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1476-5535
    Keywords: Keywords: E. coli; fermentation; induction; recombinant; expression; scale-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effects of medium composition and induction timing on expression of a chimeric fusion protein TGF-α -PE40 (TP-40) in Escherichia coli strain RR1 were examined using a complex medium at several fermentor scales. Two distinctive phases in E. coli catabolism were identified during fermentation based on preferential utilization between protein hydrolysate and glycerol. Maximum specific and volumetric productivities were achieved by inducing the culture when the cells were switching substrate utilization from protein hydrolysate to glycerol. By increasing the yeast extract concentration in the production medium, initiation of the catabolic switch was delayed until high cell mass was achieved. The final titer of TP-40 at the 15-L fermentation scale was doubled from 400 mg L−1 to 850 mg L−1 by increasing the yeast extract concentration from 1% to 4% (w/v) and delaying the time of induction. This fermentation process was rapidly scaled up in 180-L and 800-L fermentors, achieving TP-40 titers of 740 and 950 mg L−1, respectively.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 15-19 
    ISSN: 0006-3592
    Keywords: viscous fluid ; fluid dynamic study ; Xanthan solution ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Studies were conducted1 in 19-m3 fermentors (14-m3 working volume) using four Rushton turbines, four Prochem Maxflo Ts, and three Lightnin' A315s and the results in water have been reported earlier. Here, a 1.7 wt/vol% Xanthan solution has been used as the working fluid, simulating viscous broths to give Reynolds numbers (Re) between 1800 and 4500. As predicted from small-scale studies, the power numbers at these values of Re were similar to those in water. The K factor (the ratio of power draw under aerated conditions compared to non-aerated) was the same as in water at the higher values of Re, but at the lower values it fell more rapidly with increasing aeration rate and to a lower value than in water. At all times, K was higher than with Rushton turbines. Vibration characteristics were also measured. Under aerated conditions, the fermentors vibrated with an amplitude 75% to 100% less than in water due to viscous damping. With increasing air flow, the amplitude increased steadily due to the presence of very large and rapidly rising bubbles in such fluids to give values 2.5 to 3 times those in water. Nevertheless, these mechanical problems can be overcome, allowing such agitators to be used successfully in high viscosity mycelial fermentations. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 31 (1988), S. 737-742 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: For viscous mycelial fermentations it was demonstrated at the pilot-plant scale that the replacement of standard radial flow Rushton turbines with larger diameter axial-flow Prochem hydrofoil impellers significantly improved oxygen transfer efficiency. It was also determined that the Streptomyces broth under evaluation is highly shear thinning. Separate experiments using a Norcardia broth with similar Theological properties demonstrated that the oxygen transfer coefficient, KLa, can be greatly increased by use of water additions to reduce broth viscosity. These observations are consistent with the hypothesis that the improvement in oxygen transfer by changing agitator types is primarily due to an improvement in bulk mixing. A model is presented, based on the concepts of Bajpai and Reuss, which explains this improvement in performance in terms of enlargement of the well mixed micromixer region for viscous mycelial broths.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 1101-1107 
    ISSN: 0006-3592
    Keywords: simvastatin ; microbial ; hydroxylation ; fermentation ; biotransformation ; scale-up ; dissolved oxygen ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: This article describes a process for microbial hydroxylation of simvastatin by a Nocardia sp. Simvastatin (Zocor) belongs to the family of HMGCoA reductase inhibitors used as cholesterol-lowering drugs. Studies at 14 L scale showed that high substrate (simvastatin) concentrations inhibited product formation; consequently, continuous slow feeding of the substrate was introduced to maintain low residual simvastatin concentrations. Dissolved oxygen levels above 50% air saturation were desirable for the biotransformation. The process was scaled up to 19,000-L fermentors using an on-line filter sterilization system for substrate feeding. The feed rate was regulated by off-line high-pressure liquid chromatography (HPLC) assays to keep the substrate concentration below 20 mg/L. Intermittent addition of nutrients helped to boost the bioconversion rate to give final titers of 400 mg/L 6-β-hydroxymethyl simvastatin. Enrichment of the nutrient medium led to bioconversion titers of 800 mg/L 6-β-hydroxymethyl simvastatin. Bioconversion efficiencies (desired product/substrate) of 22-25% with a ratio of desired product/side products of 0.7 were obtained by this process.
    Additional Material: 16 Ill.
    Type of Medium: Electronic Resource
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