ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

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Process optimization for large-scale production of TGF-α-PE40 in recombinant Escherichia coli: effect of medium composition and induction timing on protein expression (1997)

Lee, C ; Sun, W-J ; Burgess, B W ; [et al.]

Springer

Journal of industrial microbiology and biotechnology 18 (1997), S. 260-266

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ISSN: 1476-5535

Keywords: Keywords: E. coli; fermentation; induction; recombinant; expression; scale-up

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: The effects of medium composition and induction timing on expression of a chimeric fusion protein TGF-α -PE40 (TP-40) in Escherichia coli strain RR1 were examined using a complex medium at several fermentor scales. Two distinctive phases in E. coli catabolism were identified during fermentation based on preferential utilization between protein hydrolysate and glycerol. Maximum specific and volumetric productivities were achieved by inducing the culture when the cells were switching substrate utilization from protein hydrolysate to glycerol. By increasing the yeast extract concentration in the production medium, initiation of the catabolic switch was delayed until high cell mass was achieved. The final titer of TP-40 at the 15-L fermentation scale was doubled from 400 mg L−1 to 850 mg L−1 by increasing the yeast extract concentration from 1% to 4% (w/v) and delaying the time of induction. This fermentation process was rapidly scaled up in 180-L and 800-L fermentors, achieving TP-40 titers of 740 and 950 mg L−1, respectively.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1038/sj.jim.2900382

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2

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Fluorescence sensing of fermentation parameters using fiber optics (1988)

Junker, B. H. ; Wang, D. I. C. ; Hatton, T. A.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 32 (1988), S. 55-63

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ISSN: 0006-3592

Keywords: Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: A method has been developed for measuring fermentation parameters such as dissolved oxygen, pH, and cell density that differs from traditional techniques that require electrodes and off-line samples. Fluorescent indicators, each sensitive to a single variable, are dissolved directly into a fermentation broth. A fiber-optic probe fluorimeter measures the fluorescence intensities that can then be correlated with parameter values. In addition, an integrated scatter scanning technique can be used to monitor cell density in situ. Results have been obtained using simulated baker's yeast broth and during actual baker's yeast fermentations.

Additional Material: 9 Ill.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/bit.260320109

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3

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Cultivation of virus antigen in fibroblast cells using a glass fiber bed reactor (1993)

Junker, B. H. ; Chiou, T. ; Wang, D. I. C. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 42 (1993), S. 635-642

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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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4

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Influence of strain and medium composition on filtration of escherichia coli suspensions (1994)

Junker, B. H. ; Timberlake, S. ; Bailey, F. J. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 44 (1994), S. 539-548

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ISSN: 0006-3592

Keywords: cross-flow filtration ; Escherichia coli ; cell harvesting ; fermentation ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Cross-flow filtration of Escherichia coli strains was examined at the laboratory and pilot scales using Romicon 500,000 molecular-weight-cutoff hollow fiber membranes. Both the series resistance and macrosolute polarization models were employed to compare performances. Total dissolved solids content above 90 g/L and viscosity above 1.1 × 10-3 paċ s of cell-free culture media were found to decrease average filtration fluxes by over 60% both in the absence and presence of cells. Broth filtration with culture media of dissolved solids levels below 80 g/L were influenced to a greater extent by harvest cell density. The collodial nature of the complex nutrient responsible for the total solids increase affected prediction of filtration performance. Differences in strain filterability were observed with JM109 preferred over DH5 in high solids-containing media and RR1 preferred over JM109 in low dissolved solids-containing media. Their research demonstrates the importance of cell strain and media selection in the performance of early downstream processing steps. © 1994 John Wiley & Sons, Inc.

Additional Material: 7 Ill.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/bit.260440418

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5

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Development of a recovery and recycle process for a pseudomonas lipase used for large-scale enzymatic synthesis (1993)

Junker, B. H. ; Bhupathy, M. ; Buckland, B. C.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 42 (1993), S. 487-493

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ISSN: 0006-3592

Keywords: enzyme ; lipase ; recovery ; recycle ; filtration ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Enzymes are potential catalysts for a wide range of large-scale chemical synthesis steps, particularly when the creation of a specific chiral center is desired. The efficient recycling of the enzyme catalyst and the removal of carryover impurities were crucial factors in the improvement of a stereoselective ester hydrolysis step used in the synthesis of a selective leukotriene antagonist. In this enzymatic reaction step, the substrate and product were both largely insoluble, while the enzyme was soluble in the aqueous reaction mixture. Microfiltration and ultrafiltration of the slurry reaction mother liquor indicated near 100% enzyme protein recovery, while activity recovery was about 70% to 80%. These activity losses might be accounted for by enzyme degradation (1 to 2 mg/L · h) during the 40-hour reaction period. Dissolved impurities, principally a diacid byproduct, in the enzyme recycling stream were reduced 60% to 70% by either lowering the solution pH to 4.0 or raising the solution ionic strength to 1 M. © 1993 John Wiley & Sons, Inc.

Additional Material: 5 Ill.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/bit.260420412

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6

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Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor (1994)

Junker, B. H. ; Seamans, T. C. ; Ramasubramanyan, K. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 44 (1994), S. 1315-1324

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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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An improved constraint filtering technique for inferring hidden states and parameters of a biological model (2013)

Murtuza Baker, S., Poskar, C. H., Schreiber, F., Junker, B. H.

Oxford University Press

In: Bioinformatics

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Publication Date: 2013-04-13

Description: Motivation: In systems biology, kinetic models represent the biological system using a set of ordinary differential equations (ODEs). The correct values of the parameters within these ODEs are critical for a reliable study of the dynamic behaviour of such systems. Typically, it is only possible to experimentally measure a fraction of these parameter values. The rest must be indirectly determined from measurements of other quantities. In this article, we propose a novel statistical inference technique to computationally estimate these unknown parameter values. By characterizing the ODEs with non-linear state-space equations, this inference technique models the unknown parameters as hidden states, which can then be estimated from noisy measurement data. Results: Here we extended the square-root unscented Kalman filter SR-UKF proposed by Merwe and Wan to include constraints with the state estimation process. We developed the constrained square-root unscented Kalman filter (CSUKF) to estimate parameters of non-linear state-space models. This probabilistic inference technique was successfully used to estimate parameters of a glycolysis model in yeast and a gene regulatory network. We showed that our method is numerically stable and can reliably estimate parameters within a biologically meaningful parameter space from noisy observations. When compared with the two common non-linear extensions of Kalman filter in addition to four widely used global optimization algorithms, CSUKF is shown to be both accurate and computationally efficient. With CSUKF, statistical analysis is straightforward, as it directly provides the uncertainty on the estimation result. Availability and implementation: Matlab code available upon request from the author. Contact: baker@ipk-gatersleben.de Supplementary information: Supplementary data are available at Bioinformatics online.

Print ISSN: 1367-4803

Electronic ISSN: 1460-2059

Topics: Biology , Computer Science , Medicine