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  • 1990-1994  (3)
  • animal cell culture  (1)
  • dissolved oxygen  (1)
  • fermentation  (1)
  • fibers  (1)
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  • 1990-1994  (3)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Development of a large-scale continuous substrate feed process for the biotransformation of simvastatin by Nocardia s.p. (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 1101-1107 
    Details
    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
    URL: http://dx.doi.org/10.1002/bit.260371116
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Cultivation of virus antigen in fibroblast cells using a glass fiber bed reactor (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 635-642 
    Details
    ISSN: 0006-3592
    Keywords: MRC-5 ; anchorage-dependent ; fibers ; cell culture ; hepatitis A ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The anchorage-dependent cell line, MRC-5, was cultivated successfully on glass fibers with diameters ranging from 24 to 120 μm, despite vast differences in substrate curvature. Multilayer cell growth was observed, particularly for fiber diameters 30 μm and below, which differed from the typical monolayer growth observed in T-flask cultivations. Cells were maintainable at a reduced incubation temperature and were demonstrated to support virus replication for the 21-day antigen production period. Direct microscopic observation, along with indirect calculations, indicated that only a small fraction (about 10%) of the total available fiber surface area was occupied by cells. Thus, productivity per unit surface area was replaced by productivity per unit medium volume when evaluating fiber bed performance. Antigen and protein yields, as well as nutrient uptakes, were 1.5- to 2.5-fold greater than parallel T-flask cultures when compared on this basis. Corresponding available surface area-based values were 10- to 15-fold lower for the fiber bed reactor. The multilayer cell morphology obtained in the fiber bed was attractive for antigen production when immobilized in a column reactor system. © 1993 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260420512
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 1315-1324 
    Details
    ISSN: 0006-3592
    Keywords: static mixer ; MRC-5 ; anchorage dependent ; hepatitis A ; animal cell culture ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 197s, was investigated for the production of attenuated hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor system used Charles River Biotechnological Services cabinets for monitoring and process control. Cell inoculation protocols, using 6000-10,000 cells/cm2, resulted on over 95% attachment at both the laboratory and pilot scales. Indirect monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake rates were indicative of cell growth prior to virus inoculation as well as environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm2) runs and one pilotscale (265,000 cm2) run were conducted to investigate refeeding regiments, parallel versus perpendicular element orientation, increased element surface area per unit volume, and scale-up performance. In general, lysate antigen yields achieved were similar to those of parallel T-flasks cultivated under similar conditions. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260441107
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    Paper (German National Licenses)
    Fulltext
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