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  • 1
    Electronic Resource
    Electronic Resource
    Analysis of bifurcations in continuous fermentation using recombinant microorganisms with delayed responses (1995)
    Springer
    Bioprocess and biosystems engineering 12 (1995), S. 199-203 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract When the feed rate to a fermenter is varied periodically in order to favor the growth of plasmid-containing cells, a transition may occur from the starting stationary state to another state. The resulting state may be constant or oscillatory. A generalised model based on the adaption times of plasmid-free and plasmid-harboring cells has been used. Analytical conditions have been derived for bifurcation from one nonoscillatory state to another or to an oscillatory state (Hopf bifurcation). The frequency of oscillation is shown to have an upper bound, which can be controlled by manipulating certain process parameters. The production of tryptophan synthetase by the plasmid pPLc23trpAl in E. coli is used as an example to determine the nature of the Hopf bifurcations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01767467
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Incomplete mixing in large bioreactors — a study of its role in the fermentative production of streptokinase (1996)
    Springer
    Bioprocess and biosystems engineering 14 (1996), S. 91-96 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The production of streptokinase in a batch fermentation has been analysed for the role of incomplete macromixing of the broth. The analysis is based on a kinetic model exhibiting inhibition by the substrate and a primary metabolite (lactic acid), and a mixing model comprising two continuous flow reactors (CFRs) with closed-loop recycle. The inoculum is introduced into one region (one CFR) and the mixing process determines its distribution, growth and reactivity. By varying the dilution rates of the CFRs, any degree of macromixing can be simulated. For dilution rates larger than 1.0 h−1 almost complete macromixing is achieved, for which an analogy has been drawn with micromixing. Increasing the volume of the inoculated region relative to the noninoculated region improves the maximum attainable activity of streptokinase and shortens the time for this. In such a situation an imperfectly mixed bioreactor is superior to a perfectly mixed one, implying that good productivity requires a large inoculated region and incomplete macromixing. These inferences are supported by earlier studies of fluid mixing and relaxation times in bioreactors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387962
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Start-up sensitivity to the initial state of a batch bioreactor for a recombinant Escherichia coli in a complex medium (1996)
    Springer
    Bioprocess and biosystems engineering 15 (1996), S. 215-219 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The sensitivities with respect to the initial state of five key variables describing the performance of a batch bioreactor have been computed from an experimentally validated kinetic model. The system has a recombinant Escherichia coli strain containing the plasmid pBR Eco gap, which codes for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in a complex medium. Since previous studies have shown the start-up sensitivities to be particularly important, the initial 10% of the duration of fermentation was chosen as the time span. The sensitivities of the cell mass, GAPDH and acetate increased with time while those of glucose and yeast extract remained practically constant. Acetate has a crucial role as it functions as both a product and a reactant. With no acetate in the inoculum, the sensitivities of acetate increased an order of magnitude faster than other sensitivities. However, upon addition of acetate through the inoculum, its sensitivities decreased the fastest and stabilised beyond a starting concentration of about 1 g/l whereas other sensitivities stabilised after 5 to 6 g/l of initial acetate. A three-dimensional envelope in the space of acetate concentration-time-relative sensitivity shows a locus of concentrations for minimum time-dependent acetate sensitivity; this may be maintained through fed-batch operation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369485
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    A heuristic approach to fed-batch optimisation of streptokinase fermentation (1995)
    Springer
    Bioprocess and biosystems engineering 13 (1995), S. 109-112 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Previous studies have shown that the rate of formation of streptokinase, a secondary metabolite, in batch fermentation is proportional to the specific growth rate of the biomass, which in turn is inhibited by its substrate and the primary product (lactic acid). These kinetics suggest the suitability of fed-batch operation to increase the yield of streptokinase. A near-optimal feed policy has been calculated by the chemotaxis algorithm, and it shows a substrate feed rate decreasing nonlinearly and vanishing after 11 hours. This is followed by batch fermentation for a further 8 hours, at the end of which 12% more streptokinase is generated than by purely batch fermentation. Further improvements in productivity are possible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00420437
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Analysis of bifurcations in continuous fermentation using recombinant microorganisms with delayed responses (1995)
    Springer
    Bioprocess engineering 12 (1995), S. 199-203 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  When the feed rate to a fermenter is varied periodically in order to favor the growth of plasmid-containing cells, a transition may occur from the starting stationary state to another state. The resulting state may be constant or oscillatory. A generalised model based on the adaption times of plasmid-free and plasmid-harboring cells has been used. Analytical conditions have been derived for bifurcation from one nonoscillatory state to another or to an oscillatory state (Hopf bifurcation). The frequency of oscillation is shown to have an upper bound, which can be controlled by manipulating certain process parameters. The production of tryptophan synthetase by the plasmid pPLc23trpA1 in E. coli is used as an example to determine the nature of the Hopf bifurcations. List of symbols D l/h dilution rate K m g/l Monod constant p– probability of plasmid loss per generation s g/l substrate concentration t h time T i h delay time of cells of i-th kind x i g/l concentration of cells of i-th kind Y i g/g yield coefficient of cells of i-th kind Greek symbols μ i l/h specific growth rate of i-th species μ im l/h maximum possible value of μ i τ h generalised delay time Subscripts 1 cells without plasmids 2 cells with plasmids s steady state Superscript o inlet stream
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01767467
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    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Incomplete mixing in large bioreactors – a study of its role in the fermentative production of streptokinase (1996)
    Springer
    Bioprocess engineering 14 (1996), S. 91-96 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  The production of streptokinase in a batch fermentation has been analysed for the role of incomplete macromixing of the broth. The analysis is based on a kinetic model exhibiting inhibition by the substrate and a primary metabolite (lactic acid), and a mixing model comprising two continuous flow reactors (CFRs) with closed-loop recycle. The inoculum is introduced into one region (one CFR) and the mixing process determines its distribution, growth and reactivity. By varying the dilution rates of the CFRs, any degree of macromixing can be simulated. For dilution rates larger than 1.0 h-1 almost complete macromixing is achieved, for which an analogy has been drawn with micromixing. Increasing the volume of the inoculated region relative to the noninoculated region improves the maximum attainable activity of streptokinase and shortens the time for this. In such a situation an imperfectly mixed bioreactor is superior to a perfectly mixed one, implying that good productivity requires a large inoculated region and incomplete macromixing. These inferences are supported by earlier studies of fluid mixing and relaxation times in bioreactors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387962
    Location Call Number Limitation Availability
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    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Thermostable pullulanase from a mesophilic Bacillus cereus isolate and its mutant UV7.4 (1992)
    Springer
    Biotechnology letters 14 (1992), S. 689-694 
    Details
    ISSN: 1573-6776
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A mesophilicBacillus cereus strain was isolated from soil. Since it produced fairly good amounts of extracellular pullulanase, mutations with ultraviolet light and nitrosoguanidine were done to improve the productivity. One of the second generation mutants, UV7.4, produced larger amounts of pullulanase at 37°C than most (mesophilic or thermophilic) organisms reported. The pullulanase was highly active and stable for up to one hour at 70°C. If developed further, UV7.4 can be used commercially for the saccharification of starch.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01021644
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Preliminary screening of neural network configurations for bioreactor applications (1996)
    Springer
    Biotechnology techniques 10 (1996), S. 967-970 
    Details
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A methodology and a computer code have been devised to perform a preliminary analysis of six types of neural networks commonly employed for bioreactor problems. Both static and time-varying data can be analysed, and the values of the parameters and/or sampling times can be chosen according to the system behavior. The results help to select a suitable network configuration for detailed training and application. This is illustrated for a fed-batch fermentation to produce recombinant β-galactosidase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180404
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    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Neural simulation of an unsteady state continuous recombinant fermentation with imperfect mixing (1996)
    Springer
    Biotechnology techniques 10 (1996), S. 573-578 
    Details
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A continuous fermentation based on a recombinant Escherichia coli strain producing tryptophan synthetase has been simulated by a back-propagation neural network. Data for the network were generated through known kinetics applied to a reactor model with an adjustable degree of macromixing of the broth. A network with just one hidden layer performed satisfactorily for both poor and good macromixing. The best performance was at an intermediate level of mixing, in the region of maximum productivity of the recombinant protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00157364
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    Paper (German National Licenses)
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  • 10
    Electronic Resource
    Electronic Resource
    Sensitivity analysis of fed-batch fermentation for the production of penicillin G (1992)
    Springer
    Biotechnology techniques 6 (1992), S. 9-14 
    Details
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary The mixed metabolism model of Nicolaiet al. (1991) has been used to analyse the sensitivity of fed-batch fermentation for penicillin G with respect to four parameters. The cases of fully endogenous, fully maintenance and mixed metabolisms have been studied. Sensitivities with respect to two parameters,K x andK i, were much larger than for the other two. Differences between the three kinds of metabolism were sharpest forK p. The implications of both observations are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02438679
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    Paper (German National Licenses)
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