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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 5 (1990), S. 143-153 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The batch productivity (Q TM) of the production of the nucleoside antibiotic toyocamycin (TM) by Streptomyces chrestomyceticus was increased ten-fold by selection of a UV generated mutant, optimization of pH, increasing incubation temperature from 28 °C to 36 °C, and addition of soy oil. Initial high oxygen transfer rates stimulated Q TM maxima two-fold. Antibiotic production by the mutant strain, U190, however, appeared more shear sensitive than the parent culture FCRF 341 with maximum antibiotic titer being inversely related to impellor tip velocity, T v . For this reason, scale-up could not be done at constant P/V or constant volumetric oxygen transfer. Instead, programming of impeller speed was evaluated in order to maintain optimal impeller tip velocity during scale-up. It was found that a low constant T v maintained in scale-up in geometrically similar vessels was most beneficial for duplication of optimal antibiotic productivity, Q TM. Pilot fermentations (120 dm3 scale) were used to determine coefficients of Q TM variation from oxygen uptake rate (OUR) and total CO2 evolution data for monitoring of Q TM variation during scale-up to the 12,000 dm3 scale. This technique allowed for on-line prediction of antibiotic titer and Q TM from fermentor exhaust gas data.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 5 (1990), S. 155-164 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A total cell recycling suspension perfusion reactor has been constructed for investigation of specific monoclonal antibody secretion rate of the 9.2.27 murine hybridoma under conditions of a very low growth rate. By rapidly recycling hybridoma cells using a thermostated tangential flow filter, 3.6 mg cell dry weight/cm3 could be maintained at growth rate of 〈0.05 μmax for over 250 h. Under these conditions, secretion of lactate, ammonia and l-alanine were directly related to the rate of l-glutamine supply. Monoclonal antibody accumulated in the reactor to levels in excess of 1400 μg/ cm3. Surprisingly, as specific growth rate decreased, the specific immunoglobulin secretion rate remained constant, implying that monoclonal antibody synthesis could be uncoupled from growth.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of industrial microbiology and biotechnology 23 (1999), S. 668-676 
    ISSN: 1476-5535
    Keywords: Keywords: biosensor; E. coli; immobilization; latex film; luciferase; mercury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A single-use Hg(II) patch biosensor has been developed consisting of 1.25-cm diameter patches of two acrylic vinyl acetate copolymer layers coated on polyester. The top layer copolymer was 47 μm thick whereas the bottom layer of copolymer plus E. coli cells was 30 μm thick. The immobilized E. coli HB101 cells harbored a mer-lux plasmid construct and produced a detectable light signal when exposed to Hg(II). The immobilized-cell Hg(II) biosensor had a sensitivity similar to that of suspended cells but a significantly larger detection range. The levels of mercury detected by the patches ranged from 0.1 nM to 10 000 nM HgCl2 in pyruvate buffer, and luciferase induction as a function of Hg(II) concentration was sigmoidal. Luciferase activity was detected in immobilized cells for more than 78 h after exposure of the cells to HgCl2. Addition of 1 mM D-cysteine to the pyruvate buffer increased luciferase induction more than 100-fold in the immobilized cell patches and 3.5-fold in a comparable suspension culture. The copolymer patches with immobilized cells were stable at −20°C for at least 3 months, and the Hg(II)-induced luciferase activity after storage was similar to that of samples assayed immediately after coating. Patches stored desiccated at room temperature for 2 weeks showed lower mercury-induced luciferase activity when compared to freshly prepared patches, but they still had a considerable detection range of 1 to 10 000 nM HgCl2.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 21 (1979), S. 1881-1883 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1273-1276 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 23 (1981), S. 455-460 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: An initial structured unsegregated kinetic model describing monoclonal antibody synthesis by a murine hybridoma cell line (9.2.27) grown in 1 liter batch cultures is described. The model is based on the intracellular balances of the heavy and light chain coding mRNAs, the intracellular balances of heavy and light chains and the description of the kinetics of heavy and light chain assembly. Model parameters were varied with specific growth rate in order to account for changes in the rates of antibody synthesis and secretion with entrance of the cells from the exponential into the stationary phase of growth. The parameters were varied based. on experimental data obtained in our laboratory on the variation of total cellular RNA content and the half-lives of heavy (H) and light (L) chain mRNAs with specific growth rate, and data from other investigators on immunoglobulin synthesis and secretion. The model successfully predicts the experimentally observed decrease in the intracellular heavy and light chain mRNA levels with entrance of 9.2.27 cells from the exponential into the stationary phase of growth, as well as the extracellular accumulation of antibody (IgG2a) during batch culture.
    Additional Material: 19 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Proper design of fermentation facilities and equipment modification can control the risks associated with largescale production and purification of microbially produced cytotoxic agents and oncogenic viruses. The primary biohazard risks to operators and the environment are generation of aerosols and accidental spills. Fermentation and recovery facilities can be constructed to contain these agents by installing fermentation equipment within a HEPA-filter-exhausted biological barrier. Within this barrier system, large-scale processing that generates potentially hazaradous areosols (filtration, centrifugation of transformed cells or crystal slurries, and banding of viruses) should be isolated from other operations. Isolation of equipment is often required, with provision for both chemical and biological decontamination of process wastes. Failsafe fermentor over-pressure sensors, parallel exhaust gas filtration, welded transfer lines, and modified sampling systems for elimination of aerosols can be installed on most fermentation equipment. Aerosol and spill containment by proper equipment design, coupled with appropriate personnel protective equipment and medical monitoring, make possible safe production of experimental growth factors and viruses from large-scale culture of transformed mammalian cells and production of cytotoxic antitumor antibiotics.
    Additional Material: 22 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 27 (1985), S. 1-9 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A cybernetic framework is presented which views microbial response in multiple substrate environments as a judicious investment of cellular resources in synthesizing different key proteins according to an optimal regulatory strategy. A mathematical model is developed within the cybernetic framework for the diauxic growth of Klebsiella pneumoniae on a mixture of D-glucose and D-xylose. The “bang-bang” optimal policy describes well the experimental observations obtained using a fermenter coupled to an Apple II microcomputer. Striking variations in respiratory levels are observed experimentally during the switching of the cell's adaptive machinery for the utilization of the less preferred substrate.
    Additional Material: 7 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 34 (1989), S. 1023-1036 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: On-line determination of expression rates from cloned genes in Escherichia coli and of plasmid copy number would be useful for monitoring accumulation of non-secreted proteins. As an initial model for monitoring gene expression in intact cells, a non-gene-fusion enzyme-based indicator plasmid has been constructed containing the phoA gene coding for alkaline phosphatase (AP) in pUCIS and pACYC184. The activity of AP can be rapidly determined in permeabilized cells. A flow injection analysis (FIA) assay has been developed which allows the direct real-time measurement of the AP activity during cell growth. A model target gene coding for E. coli cyanase (cynS) has been inserted in order to determine the ratio between the expression of the target and indicator, AP. A linear relationship has been found between plasmid copy number and AP activity for the high-copy pUC vector. To minimize indicator expression, transcription terminators have been inserted between the cynS and phoA genes, altering the target-to-indicator ratio by 10- to 40-fold. These vectors may be useful for the rapid continuous determination of plasmid copy number and target gene expression for nonsecreted proteins and would overcome the limitations of in situ probe biosensors for real-time determination of the accumulation of proteins from cloned genes in E. coli.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
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