Tetracycline-regulated overexpression of glycosyltransferases in Chinese hamster ovary cells.

Abstract:

:The glycosylation patterns of recombinant therapeutic glycoproteins can be engineered by overexpression of glycosyltransferases in the host cells used for glycoprotein production. Most prior glycosylation engineering experiments have involved constitutive expression of cloned glycosyltransferases. Here we use tetracycline-regulated expression of two glycosyltransferases, N-acetylglucosaminlytransferases III and V (GnTIII and GnTV) to manipulate glycoform biosynthesis in Chinese hamster ovary (CHO) cells and to study the effect of glycosyltransferase overexpression on this host. The amount of GnTIII and GnTV in these cells, and the glycosylation patterns of several cellular glycoproteins, could be controlled simply by manipulating the concentration of tetracycline in the culture medium. Using this system, it was found that overexpression of either GnTIII or GnTV to high levels led to growth inhibition and was toxic to the cells, indicating that this may be a general feature of glycosyltransferase overexpression. This phenomenon has not been reported previously, probably due to the widespread use of constitutive promoters, and should be taken into account when designing vectors for glycosylation engineering. The growth inhibition effect sets an upper limit to the level of glycosyltransferase overexpression, and may thereby also limit the maximum extent of in vivo modification of poorly accessible glycosylation sites. Also, such inhibition implies a bound on constitutive glycosyltransferase expression which can be cloned.

journal_name

Biotechnol Bioeng

authors

Umaña P,Jean-Mairet J,Bailey JE

subject

Has Abstract

pub_date

1999-12-05 00:00:00

pages

542-9

issue

5

eissn

0006-3592

issn

1097-0290

pii

10.1002/(SICI)1097-0290(19991205)65:5<542::AID-BIT

journal_volume

65

pub_type

杂志文章
  • Ethanol and toluene removal in a horizontal-flow anaerobic immobilized biomass reactor in the presence of sulfate.

    abstract::In this study it is reported the operation of a horizontal-flow anaerobic immobilized biomass (HAIB) reactor under sulfate-reducing condition which was also exposed to different amounts of ethanol and toluene. The system was inoculated with sludge taken from up-flow anaerobic sludge blanket (UASB) reactors treating re...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20509

    authors: Cattony EB,Chinalia FA,Ribeiro R,Zaiat M,Foresti E,Varesche MB

    更新日期:2005-07-20 00:00:00

  • A theoretical method to improve and optimize the design of bioartificial livers.

    abstract::Bioartificial livers (BALs) are a potentially effective countermeasure against liver failure, particularly in cases of acute or fulminant liver failure. It is hoped these devices can sustain a patient's liver function until recovery or transplant. However, no large-scale clinical trial has yet proven that BALs are par...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22765

    authors: Davidson AJ,Ellis MJ,Chaudhuri JB

    更新日期:2010-08-15 00:00:00

  • Maximizing neotissue growth kinetics in a perfusion bioreactor: An in silico strategy using model reduction and Bayesian optimization.

    abstract::In regenerative medicine, computer models describing bioreactor processes can assist in designing optimal process conditions leading to robust and economically viable products. In this study, we started from a (3D) mechanistic model describing the growth of neotissue, comprised of cells, and extracellular matrix, in a...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26500

    authors: Mehrian M,Guyot Y,Papantoniou I,Olofsson S,Sonnaert M,Misener R,Geris L

    更新日期:2018-03-01 00:00:00

  • Fungal treatment of mechanical pulps-its effect on paper properties.

    abstract::Refiner mechanical pulp was biologically treated with several higher fungi in order to test their potential for increasing the strength of paper. It was among the white-rot fungi that the best results were obtained. Polyporus versicolor gave the best overall improvement in handsheet properties with no reduction in tea...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260240913

    authors: Pilon L,Barbe MC,Desrochers M,Jurasek L,Neumann PJ

    更新日期:1982-09-01 00:00:00

  • Cascading effect in bioprocessing-The impact of mild hypothermia on CHO cell behavior and host cell protein composition.

    abstract::A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture conditions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26437

    authors: Goey CH,Tsang JMH,Bell D,Kontoravdi C

    更新日期:2017-12-01 00:00:00

  • A study of D-lactate and extracellular methylglyoxal production in lactate re-utilizing CHO cultures.

    abstract::In large-scale mammalian cell culture, the key toxic by-products assessed and monitored are lactate and ammonia. Often no distinction between the two isoforms of lactate is made. Here, we present profiles of both D- and L-lactate. D-Lactate is the end molecule of the methylglyoxal pathway. D-Lactate unlike L-lactate i...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22757

    authors: Paoli T,Faulkner J,O'kennedy R,Keshavarz-Moore E

    更新日期:2010-09-01 00:00:00

  • Engineering CHO cells to overexpress a secreted reporter protein upon induction from mouse mammary tumor virus promoter.

    abstract::The mouse mammary tumor virus (MMTV) promoter is induced by the addition of a glucocorticoid hormone or analog such as dexamethasone. The hormone binds to its specific transcription factor, glucocorticoid receptor (GR), and the activated complex then binds to the glucocorticoid response elements (GREs) in the enhancer...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:

    authors: James RI,Elton JP,Todd P,Kompala DS

    更新日期:2000-01-20 00:00:00

  • Generation of stable, high-producing CHO cell lines by lentiviral vector-mediated gene transfer in serum-free suspension culture.

    abstract::Lentivirus-derived vectors (LVs) were studied for the generation of stable recombinant Chinese hamster ovary (CHO) cell lines. Stable pools and clones expressing the enhanced green fluorescent protein (eGFP) were selected via fluorescence-activated cell sorting (FACS). For comparison, cell pools and cell lines were al...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22968

    authors: Oberbek A,Matasci M,Hacker DL,Wurm FM

    更新日期:2011-03-01 00:00:00

  • A multi-site metastasis-on-a-chip microphysiological system for assessing metastatic preference of cancer cells.

    abstract::Metastatic disease remains one of the primary reasons for cancer-related deaths, yet the majority of in vitro cancer models focus on the primary tumor sites. Here, we describe a metastasis-on-a-chip device that houses multiple bioengineered three-dimensional (3D) organoids, established by a 3D photopatterning techniqu...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26871

    authors: Aleman J,Skardal A

    更新日期:2019-04-01 00:00:00

  • Quantitative and kinetic study of oxidative stress regulons using green fluorescent protein.

    abstract::Potentially damaging reactive oxygen species (ROS) are involved in a number of pathways ranging from signal transduction to apoptosis. Cells have adapted this alteration in redox status into a complex regulatory mechanism. ROS are specifically able to induce the expression of a multitude of genes. We constructed and c...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20389

    authors: Lu C,Albano CR,Bentley WE,Rao G

    更新日期:2005-03-05 00:00:00

  • Nitrogen polishing in a fully anoxic anammox MBBR treating mainstream nitritation-denitritation effluent.

    abstract::As nitrogen discharge limits are becoming more stringent, short-cut nitrogen systems and tertiary nitrogen polishing steps are gaining popularity. For partial nitritation or nitritation-denitritation systems, anaerobic ammonia oxidation (anammox) polishing may be feasible to remove residual ammonia and nitrite from th...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.25826

    authors: Regmi P,Holgate B,Miller MW,Park H,Chandran K,Wett B,Murthy S,Bott CB

    更新日期:2016-03-01 00:00:00

  • Production of cellulases by Trichoderma reesei QM 9414 in fed-batch and continuous-flow culture with cell recycle.

    abstract::The scope in improving enzyme productivities from the cellulose fermentation process is examined in laboratory-scale fermentors. The maximum productivity (30 IU/liter hr) is attained in a continuous-culture process with cell recycle using modified medium containing 0.5% cellulose. Optimum dilution rate and recycle rat...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260210213

    authors: Ghose TK,Sahai V

    更新日期:1979-02-01 00:00:00

  • High-efficiency protein delivery into transfection-recalcitrant cell types.

    abstract::Intracellular delivery of functional proteins is of great interest for basic biological research as well as for clinical applications. Transfection is the most commonly used method, however, it is not applicable to large-scale manipulation and inefficient in important cell types implicated in biomedical applications, ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.27245

    authors: Li Z,Cai Z,Fu W,Liu Y,Tian C,Wang H,Fu T,Wu Z,Wu D,Jin Y,Cheng Z,Terada N,Liu L,Wu W,Jin S,Bai F

    更新日期:2020-03-01 00:00:00

  • C-terminal lysine variants in fully human monoclonal antibodies: investigation of test methods and possible causes.

    abstract::The C-terminal lysine variation is commonly observed in biopharmaceutical monoclonal antibodies. This modification can be important since it is found to be sensitive to the production process. The methods commonly used to probe this charge variation, including IEF, cIEF, ion-exchange chromatography, and LC-MS, were ev...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.21855

    authors: Dick LW Jr,Qiu D,Mahon D,Adamo M,Cheng KC

    更新日期:2008-08-15 00:00:00

  • Cell growth and differentiation on feeder layers is predicted to be influenced by bioreactor geometry.

    abstract::Tissue function is comprised of a complex interplay between biological and physicochemical rate processes. The design of bioreactors for tissue engineering must account for these processes simultaneously in order to obtain a bioreactor that provides a uniform environment for tissue growth and development. In the prese...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0290(19960605)50:5<479::AID-BIT

    authors: Peng CA,Palsson BØ

    更新日期:1996-06-05 00:00:00

  • Quantitative analysis of biofilm thickness variability.

    abstract::The thickness variability of biofilms of Pseudomonas aeruginosa, Klebsiella pneumoniae, and the binary population combination of these two species was quantified. The experimental method involved cryoembedding biofilms with a commercial tissue embedding agent, sectioning, and applying image analysis to construct thick...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260450607

    authors: Murga R,Stewart PS,Daly D

    更新日期:1995-03-20 00:00:00

  • Kinetic effects of simultaneous inhibition by substrate and product.

    abstract::The starting point for the present investigations was the finding that increasing influent concentrations from 10 to 380 mmol/L glucose decreased the attainable growth rate of an acidogenic population in continuous culture from 0.52 to 0.05 h(-1) To account for this phenomenon, a new kinetic model is developed that co...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260310714

    authors: Van Den Heuvel JC,Beeftink HH

    更新日期:1988-05-01 00:00:00

  • Effects of oxygen and nutrients limitation on ajmalicine production and related enzyme activities in high density cultures of Catharanthus roseus.

    abstract::Oxygen and nutrient limitation was investigated in order to identify the origin of a lower specific ajmalicine production in Catharanthus roseus cultures at high cell densities in an induction medium. The effect of oxygen limitation was explored by comparing two identically aerated and agitated high cell density biore...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260440409

    authors: Schlatmann JE,Moreno PR,Vinke JL,Ten Hoopen HJ,Verpoorte R,Heijnen JJ

    更新日期:1994-08-05 00:00:00

  • Analysis of conformational states of Candida rugosa lipase in solution: implications for mechanism of interfacial activation and separation of open and closed forms.

    abstract::In this study, an analysis of the transition between the inactive ("closed") and active ("open") conformations of Candida rugosa lipase in solution is performed using irreversible enzyme inhibitors, cyclic saligenin phosphates. It is shown that >90% inhibition of the enzyme activity toward water-soluble substrates (es...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/1097-0290(20010105)72:1<108::aid-bit14>3.0

    authors: Turner NA,Needs EC,Khan JA,Vulfson EN

    更新日期:2001-01-05 00:00:00

  • A comparison of oxygenation methods fro high-density perfusion culture of animal cells.

    abstract::A perfusion culture system was developed to investigate the oxygenation of high-density hybridoma cell cultures. The culture system was composed of a stirred-tank bioreactor and an external microfiltration hollow fiber cartridge for medium perfusion. Cell growth and antibody production were examined with large bubble ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260410702

    authors: Zhang S,Handa-Corrigan A,Spier RE

    更新日期:1993-03-25 00:00:00

  • On-line gas analysis in animal cell cultivation: I. Control of dissolved oxygen and pH.

    abstract::To monitor gas reaction rates in animal cell culture at constant dissolved oxygen concentration (DO) and constant pH it was necessary to develop improved control methods. Decoupling of both controllrs was obtained by manipulation of molar fractions of oxygen and carbon dioxide in the gas phase. Two pairs of DO and pH ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260450107

    authors: Oeggerli A,Eyer K,Heinzle E

    更新日期:1995-01-05 00:00:00

  • Membrane-attached biofilms for VOC wastewater treatment. II: Effect of biofilm thickness on performance.

    abstract::This article reports a study of the performance of membrane-attached biofilms grown in a single tube extractive membrane bioreactor (STEMS) used for the treatment of a synthetic wastewater containing a toxic VOC (1,2-dichloroethane [DCE]). Mass balances show that complete mineralization of DCE was achieved, and that t...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260470111

    authors: Dos Santos LM,Livingston AG

    更新日期:1995-07-05 00:00:00

  • Metabolic flux modeling of detoxification of acetic acid by Ralstonia eutropha at slightly alkaline pH levels.

    abstract::Ralstonia eutropha grows on and produces polyhydroxyalkanoates (PHAs) from fermentation acids. Acetic acid, one major organic acid from acidogenesis of organic wastes, has an inhibitory effect on the bacterium at slightly alkaline pH (6 g HAc/L at pH 8). The tolerance of R. eutropha to acetate, however, was increased ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.1080

    authors: Yu J,Wang J

    更新日期:2001-06-20 00:00:00

  • High-yield method for immobilization of enzymes.

    abstract::Two types of polyethylenimine-coated glass microbeads (13-44 micrometer) were synthesized and used for the immobilization of glucose oxidase from Aspergillus niger and catalase from A. niger and beef liver. The two types of beads were distinguishable by differences in their surface topography. Immobilizations were per...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260220203

    authors: Wasserman BP,Hultin HO,Jacobson BS

    更新日期:1980-02-01 00:00:00

  • Expanded bed adsorption/desorption of proteins with Streamline Direct CST I adsorbent.

    abstract::Streamline Direct CST I is a new type of ion exchanger with multi-modal functional groups, specially designed for an expanded bed adsorption (EBA) process, which can capture directly the proteins from the high ionic strength feedstocks with a high binding capacity. In this study, an experimental study is carried out f...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20952

    authors: Li P,Xiu G,Mata VG,Grande CA,Rodrigues AE

    更新日期:2006-08-20 00:00:00

  • Kinetics and mechanism of dissimilative Fe(III) reduction by Pseudomonas sp. 200.

    abstract::The kinetics and mechanism of Fe(III) reduction to Fe(II) were studied in pure batch cultures of Pseudomonas sp. 200. The rate of iron reduction has been mechanistically related to aqueous phase iron speciation. In the absence of microbial activity the iron reduction rate was negligible. Initial rates of microbial iro...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260281110

    authors: Arnold RG,Olson TM,Hoffmann MR

    更新日期:1986-11-01 00:00:00

  • Effect of membrane morphology and operation on protein deposition in ultrafiltration membranes.

    abstract::Membrane morphology is compared to protein depostion under passive adsorption and ultrafiltration conditions. Solute resistance of protein deposits for membranes of varying roughness, structure, and permeability can vary dramatically with operating conditions. Using Brunauer-Emmett-Teller adsorption isotherm (BET), st...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260470208

    authors: Chen V,Kim KJ,Fane AG

    更新日期:1995-07-20 00:00:00

  • A mechanistic model of the enzymatic hydrolysis of cellulose.

    abstract::A detailed mechanistic model of enzymatic cellulose hydrolysis has been developed. The behavior of individual cellulase enzymes and parameters describing the cellulose surface properties are included. Results obtained for individual enzymes (T. reesei endoglucanase 2 and cellobiohydrolase I) and systems with both enzy...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22789

    authors: Levine SE,Fox JM,Blanch HW,Clark DS

    更新日期:2010-09-01 00:00:00

  • Ethanol fermentation in a continuous tower fermentor.

    abstract::A mutant of Saccharomyces cerevisiae, which forms large, multicellular flocs in liquid culture, rapidly fermented media containing high concentrations of glucose (100-180 g/L) in a continuous nonaerated tower fermentor at 30 degrees C. The fermentor operated continuously for seven months. Batch and tower fermentor dat...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260260717

    authors: Jones ST,Korus RA,Admassu W,Heimsch RC

    更新日期:1984-07-01 00:00:00

  • Gas sensing in microplates with optodes: influence of oxygen exchange between sample, air, and plate material.

    abstract::Microplates with integrated optical oxygen sensors are a new tool to study metabolic rates and enzyme activities. Precise measurements are possible only if oxygen exchange between the sample and the environment is known. In this study we quantify gas exchange in plastic microplates. Dissolved oxygen was detected using...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20348

    authors: Arain S,Weiss S,Heinzle E,John GT,Krause C,Klimant I

    更新日期:2005-05-05 00:00:00