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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Fermentation and Bioengineering 76 (1993), S. 487-492 
    ISSN: 0922-338X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-5535
    Keywords: Actinomycete ; Biotransformation ; pH control ; Magnesium sulfate ; MK-733 ; Simvastatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary An actinomycete (MA 6474, ATCC 53828) isolated from a soil sample (Mutare, Zimbabwe) was found to biotransform the sodium salt of Simvastatin (MK-733) to 6-α-hydroxymethyl MK-733, 6-β-hybroxymethyl MK-733, and 6-ring-hydroxy MK-733. The bioconversion efficiency to the desired compound, 6-α-hydroxymethyl MK-733, was enhanced by optimizing the physico-chemical parameters of the process. In shake flask cultures, addition of magnesium (0.125 mg/l Mg SO4·7H2O) to the medium resulted in a five-fold increase in the rate of bioconversion to the α diastereomer. The ratio of bioconversion products (6-α-hydroxymethyl, 6-β-hydroxymethyl, and 6-ring-hydroxy MK-733) was regulated by pH. Process improvements and scale up in 23-1 fermentors, which consisted of a controlled addition of substrate (MK-733), resulted in a 2-fold increase in alpha diastereomer Production (42 vs. 79 U/ml) and a 23-fold rate increase in the formation of α-diastereomer. A high diastereomeric ratio (α: β=9∶1) facilitated downstream processing.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of industrial microbiology and biotechnology 7 (1991), S. 215-220 
    ISSN: 1476-5535
    Keywords: Fermentation monitoring ; Automatic sampling ; Aseptic sampling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary An efficient, aseptic method of obtaining whole broth fermentation samples was developed based on a piston-valve, a local sample loop, and an ability to drive the entire sample volume with sterile air through a sample line and into a remote tube. The configuration delivers 10-ml samples 10 m away with about 4 ml of broth wasted in the sampling process. An autosampler was enhanced and programmed to control acquisition into chilled tubes. The autosampler-based system represents a convenient way to provide frequent samples to profile intracellular and extracellular components for yeast and bacterial fermentations. A configuration to provide sampling from six fermentors with a multi-rack autosampler will be presented.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-5535
    Keywords: Nocardia lactamdurans ; Secondary metabolism ; Protease ; Lipase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary An efrotomycin fermentation was characterized through physical, chemical and biochemical studies. Growth of the actinomycete,Nocardia lactamdurans occurred during the first 50 h of the fermentation cycle at the expense of glucose, protein, and triglycerides. The initiation of efrotomycin biosynthesis was observed when glucose dropped to a low concentration. Upon glucose depletion, cell growth ceased and a switch in the respiratory quotient occurred. Efrotomycin biosynthesis was supported by the utilization of soybean oil and starch. Analysis of triglyceride metabolism showed that no diglycerides or monoglycerides accumulated during the fermentation. The activity of extracellular enzymes (lipase, protease, and amylase) increase during the cell growth phase and decreased significantly after 150 h. The concentrations of DNA, tetrahydro-vitamin K2 (a membrane component), and free amino acids in the supernatant increased dramatically late in the fermentation cycle (225 h), indicating massive cell lysis. During this same time period, a reduction in cellular respiratory activity and efrotomycin biosynthesis were observed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of industrial microbiology and biotechnology 6 (1990), S. 279-284 
    ISSN: 1476-5535
    Keywords: Fermentation ; Nocardia ; Bioconversion ; Avermectin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary The bioconversion of avermectin to its 27-hydroxy derivative is achieved withNocardia autotrophica subsp.canberrica. The approach of increasing bioconversion productivity rather than efficiency was adopted in these studies. Process improvement studies focused on the physico-chemical conditions of the fermentation, examined initially at the shake-flask scale. Bioconversion yields were affected by pH, substrate concentration, time of substrate addition, substrate solubilization, carbon to nitrogen ratio, and medium strength. Optimization of these parameters resulted in a 8-fold process improvement. During pre scale-up studies, the sensitivity of this bioconversion to the antifoam employed was demonstrated and lard oil was selected as giving the best results. Additional process changes were required during scale-up efforts in larger vessels, including replacement of the original substrate solvent with dimethylsulfoxide.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Isolation of a lipase produced by Pseudomonas aeruginosa (MW 29,000) employed crossflow microfiltration for production of a cell-free enzyme solution and crossflow ultrafiltration for concentration of the enzyme and removal of low molecular weight impurities. Poor flux and enzyme permeation were measured during initial screening of various microfiltration membrane types for isolation of the enzyme from a peptonized-milk-based broth; the results suggested that a soluble broth component was forming a gel layer which controlled both hydraulic flux and enzyme permeation. Reformulation of the fermentation medium resulted in enhanced performance, obtaining fluxes of 40 l/h m2 and enzyme permeation of 50% on hydrophilically-modified PVDF membranes and resulted in a feasible clarification process. Enzyme permeation remained constant with respect to activity in the feed, rather than being proportional to activity in the retentate; it was hypothesized that this resulted from a concomitant concentration of the gel-forming components with cell concentration. Concentration of the clarified enzyme solution was performed using 30 000 MWCO regenerated cellulose membranes. Complete enzyme retention and high flux (57 l/h m2) were maintained through a 130-fold concentration of the microfiltrate. As both systems were taken to the 100 and 1000 l scales, similar filtration performances were obtained with system hold-up volume and pump cavitation becoming important considerations at the larger scales. Excellent reproducibility was observed in a series of eight large-scale experiments.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0141-0229
    Keywords: Biotransformation ; biocatalysis ; fermentation ; leukotriene receptor antagonist ; lipase
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Physostigmine is a plant alkaloid of great interest as a therapeutic candidate for the treatment of Alzheimer's disease. Fortunately, this compound is also produced by Streptomyces griseofuscus NRRL 5324 during submerged cultivation. A fermentation process that used chemically defined medium was therefore developed for its production. By means of statistical experimentation, the physostigmine titer was quickly increased from 20 mg/l to 520 mg/l with a culture growth of 19 gl dry cell weight on the shake-flask scale. Further medium optimization resulted in a yield of 790 mg/l in a 23-l bioreactor using a batch process. A titer of 880 mg/l was attained during scale-up in a 800-l fermentor by employing a nutrient-feeding strategy. This production represents a 44-fold increase over the yield from the initial process in shake-flasks. The defined-medium fermentation broth was very amenable to downstream processing.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Physostigmine is a plant alkaloid of great interest as a therapeutic candidate for the treatment of Alzheimer’s disease. Fortunately, this compound is also produced by Streptomyces griseofuscus NRRL 5324 during submerged cultivation. A fermentation process that used chemically defined medium was therefore developed for its production. By means of statistical experimentation, the physostigmine titer was quickly increased from 20 mg/l to 520 mg/l with a culture growth of 19 gl dry cell weight on the shake-flask scale. Further medium optimization resulted in a yield of 790 mg/l in a 23-l bioreactor using a batch process. A titer of 880 mg/l was attained during scale-up in a 800-l fermentor by employing a nutrient-feeding strategy. This production represents a 44-fold increase over the yield from the initial process in shake-flasks. The defined-medium fermentation broth was very amenable to downstream processing.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of industrial microbiology and biotechnology 15 (1995), S. 414-417 
    ISSN: 1476-5535
    Keywords: fermentation ; scale up ; secondary metabolite ; physostigmine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A reliable and scalable fermentation process was developed for production of the acetylcholine esterase inhibitor physostigmine employingStreptomyces griseofuscus NRRL 5324. Initial fermentation in small-scale bioreactors reached physostigmine levels of approximately 60 mg L−1 after 139 h. Optimization of both process operating parameters and production medium composition rapidly yielded a seven-fold increase in physostigmine titer. The scaled up process routinely produced physostigmine titers of approximately 400 mg L−1 during a fermentation cycle of 180 h, and supported the rapid production of large amounts of physostigmine. A physostigmine production of 500 mg L−1 representing an eight-fold improvement over the original performance, was achieved using a glucose/ammonium fed-batch process.
    Type of Medium: Electronic Resource
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