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  • 1990-1994  (2)
  • animal cell culture  (1)
  • dissolved oxygen  (1)
  • 1
    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
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 1315-1324 
    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
    Library Location Call Number Volume/Issue/Year Availability
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