Abstract:
:The impact of process environment changes on process performance is one of the most crucial process safety issues when cultivating mammalian cells in a bioreactor. In contrast, directed shifting of process parameters can also be used as an optimization tool providing higher cell and product yields. Compared to other strategies that also aim on the regulation of cell growth and protein expression process parameter shifts can be easily performed without reagent addition or even genetic modification of the host cell line. However, a successful application of changing process conditions implies a profound understanding of the provoked physiological changes within the cells. In a systematic approach we varied the dissolved oxygen tension (DOT), pH, and temperature of CHO cultures in controlled bioreactors and investigated the impact on growth, productivity, metabolism, product quality and cell cycle distribution using a recombinant CHO cell line expressing the highly glycosylated fusion protein Epo-Fc. We found the reduction of cultivation temperature and the reduction of (external) pH to exert the most significant effects on process performance by mainly reducing cell growth and metabolism. With respect to the cell line used we identified a set of parameters capable of affecting cell proliferation in favor of an increased specific productivity and total product yield. The well directed alteration of the process environment has emerged as a tool adequate for further process optimization applying a biphasic cultivation strategy.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Trummer E,Fauland K,Seidinger S,Schriebl K,Lattenmayer C,Kunert R,Vorauer-Uhl K,Weik R,Borth N,Katinger H,Müller Ddoi
10.1002/bit.21013subject
Has Abstractpub_date
2006-08-20 00:00:00pages
1033-44issue
6eissn
0006-3592issn
1097-0290journal_volume
94pub_type
杂志文章abstract::PHA, a naturally occurring biopolymer produced by a wide range of microorganisms, is known for its applications as bioplastic. In recent years the use of agro-industrial wastewater as substrate for PHA production by bacterial enrichments has attracted considerable research attention. Crude glycerol as generated during...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.24991
更新日期:2013-12-01 00:00:00
abstract::In enzymatic lysis of yeast for the recovery of intracellular proteins, the rupture of whole cells is caused by the action of a lytic system consisting primarily of protease and glucanase. A first-principles mechanism for the lytic reaction based on a two-layer model of the wall structure and a burst model for the dis...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260320905
更新日期:1988-10-20 00:00:00
abstract::A transient, two-culture model simulating methane production from biomass has been developed. The simulator, based partially on the work by Andrews and McCarty, is capable of calculating the hydrolysis products of several common organic materials, accommodating various substrate feeding modes, and simulating the trans...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260240903
更新日期:1982-09-01 00:00:00
abstract::Optically pure compounds are important in the synthesis of fine chemicals. Using directed evolution of enzymes to obtain biocatalysts that can selectively produce high-value chiral chemicals is often time-, money-, and resource-intensive; traditional semi-rational designs based on structural data and docking experimen...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26484
更新日期:2018-03-01 00:00:00
abstract::Steady-state simulations using our previously developed structured kinetic model of antibody synthesis and secretion by hybridoma cells are used here in conjunction with factorial design analysis to identify intracellular parameters important in determining the specific antibody secretion rate and predict the dependen...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260390302
更新日期:1992-02-05 00:00:00
abstract::The glycerol fed-batch fermentation by Klebsiella pneumoniae CGMCC 1.6366 exhibited the sequential synthesis of products, including acetate, 1,3-propanediol (1,3-PD), 2,3-butanediol, ethanol, succinate, and lactate. The dominant flux distribution was shifted from acetate formation to 1,3-PD formation in early- exponen...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21830
更新日期:2008-08-01 00:00:00
abstract::Plant cell walls are composed primarily of cellulose, hemicelluloses, lignins, and pectins. Of these components, lignins exhibit unique chemistry and physiological functions. Although lignins can be used as a product feedstock or as a fuel, lignins are also generally seen as a barrier to efficient enzymatic breakdown ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21959
更新日期:2008-12-01 00:00:00
abstract::Several experimental data on continuous cultures of hybridoma cells show that monoclonal antibody productivity is a decreasing function of dilution rate. It has been suggested that this unusual behavior may be due to the arrest of a fraction of cycling cells at a critical point of Phase G(1). Although this hypothesis ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260421109
更新日期:1993-12-01 00:00:00
abstract::In this work, it was discovered that the stability of mRNA in a cell-free extract could be controlled by using engineered T7 terminator sequences. Specifically, it was found that mRNA stability gradually decreased as the length of the stem structure of the T7 terminator was reduced sequentially. As a result of the con...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21884
更新日期:2008-10-01 00:00:00
abstract::Many sites of environmental concern contain groundwater contaminated with nonaqueous phase liquids (NAPL). In such sites interfacial processes may affect both the equilibrium and kinetic behavior of the system. In particular, insoluble hydrocarbon partitioning and microbial biodegradation of insoluble hydrocarbon are ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(sici)1097-0290(19990520)63:4<401::aid-bit
更新日期:1999-05-20 00:00:00
abstract::The key objective for recombinant protein production in bacteria is the maximum exploitation of the cell factory's potential, whereby often strong expression vectors are used to increase product yield. If the metabolic load caused by recombinant expression exceeds the host's capacity, the system exhausts itself, resul...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10104
更新日期:2002-01-20 00:00:00
abstract::In this study, the inhibitory effects and anaerobic biotransformation of acrylic acid in computer-controlled pH-stat completely stirred tank reactors (CSTRs) with two different cultures, namely unacclimated and acrylate-acclimated acetate-enriched Methanosarcina and homogenized (crushed) granular cultures, were invest...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(sici)1097-0290(19990120)62:2<200::aid-bit
更新日期:1999-01-20 00:00:00
abstract::The production of soluble microbial products (SMP) in anaerobic systems was evaluated using chemostat reactors. Results from steady-state and tracer experiments with (14)C-glucose and (14)C-acetate showed that significant amounts of SMP were produced during the acidogenesis of glucose, but that SMP did not accumulate ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260440904
更新日期:1994-11-05 00:00:00
abstract::Detachment from biofilms was evaluated using a mixed culture biofilm grown on primary wastewater in a tube reactor. The growth of biofilms and the detachment of biomass from biofilms are strongly influenced by hydrodynamic conditions. In a long-term study, three biofilms were cultivated in a biofilm tube reactor. The ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10503
更新日期:2003-03-05 00:00:00
abstract::In glutamic acid fermentation, the molasses feeding policy and time of penicillin addition significantly affected glutamic acid production, and a fuzzy supervisory control system was developed for their quasi-optimal regulation.From the trend of the experimental data, production rules and membership functions of fuzzy...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260440113
更新日期:1994-06-05 00:00:00
abstract::Dihydrofolate reductase (DHFR) system is used to amplify the product gene to multiple copies in Chinese Hamster Ovary (CHO) cells for generating cell lines which produce the recombinant protein at high levels. The physiological changes accompanying the transformation of the non-protein secreting host cells to a high p...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25117
更新日期:2014-03-01 00:00:00
abstract::Batch fermentations of glucose to ethanol by Z. Mobilis.(ATCC 10988) were examined in several semidefined nutrient media. The measurement of acid produced by the microorganism was used to study its transient fermentation characteristics. Limitation of nitrogen source in the semidefined medium of Rogers and coworkers(2...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260310803
更新日期:1988-05-20 00:00:00
abstract::Trypsin and alpha-chymotrypsin were immobilized by gelentrapment in polyacrylamide cross-linked with N,N(1)-methylenebisacrylamide. The immobilized enzymes are catalytically efficient in suspensions of reverse micelles formed in isooctane by bis(2-ethylhexyl) sodium sulfosuccinate (AOT) and water. Both entrapped enzym...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260331008
更新日期:1989-04-20 00:00:00
abstract::Chromatography is the method of choice for the separation of proteins, at both analytical and preparative scale. Orthogonal purification strategies for industrial use can easily be implemented by combining different modes of adsorption. Nevertheless, with flexibility comes the freedom of choice and optimal conditions ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.24738
更新日期:2013-03-01 00:00:00
abstract::A specially designed model reactor based on a 42-L laboratory fermentor was equipped with six stirrers (Rushton turbines) and five cylindrical disks. In this model reactor, the mixing time, Theta(90), turned out to be 13 times longer compared with the 42-L standard laboratory fermentor fitted with two Rushton turbines...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(sici)1097-0290(19990905)64:5<599::aid-bit
更新日期:1999-09-05 00:00:00
abstract::The feasibility of continuous ester synthesis in a membrane bioreactor (MBR) by a recombinant cutinase from Fusarium solani pisi was investigated, using the optimal conditions previously attained by medium engineering. The objective was to analyze the MBR behavior as a differential or an integral reactor. The main com...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/1097-0290(20010120)72:2<127::aid-bit1>3.0.
更新日期:2001-01-20 00:00:00
abstract::13C metabolic flux analysis (MFA) is based on carbon-labeling experiments where a specifically (13)C labeled substrate is fed. The labeled carbon atoms distribute over the metabolic network and the label enrichment of certain metabolic pools is measured by using different methods. Recently, MS methods have been dramat...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10909
更新日期:2004-02-05 00:00:00
abstract::This communication demonstrates that two-phase aqueous mixed (nonionic/ionic) micellar systems have the potential for improving the separation of proteins from viruses. Specifically, two separation experiments were performed to show that the addition of the anionic surfactant sodium dodecyl sulfate (SDS) to the two-ph...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10377
更新日期:2002-10-20 00:00:00
abstract::RNA sequencing (RNASeq) has been widely used to associate alterations in Chinese hamster ovary (CHO) cell gene expression with bioprocess phenotypes; however, alternative messenger RNA (mRNA) splicing, has thus far, received little attention. In this study, we utilized RNASeq for transcriptomic analysis of a monoclona...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.27365
更新日期:2020-08-01 00:00:00
abstract::Seven different supports were compared in solid-phase S(N)Ar and S(N)2 macrocyclization reactions. Product purities were assayed for a relatively facile ring-closure process to give products 1 and 3. Some less-facile ring-closure reactions give the undesired dimeric macrocyclization by-products 2; some of these more-d...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(sici)1097-0290(200024)71:1<3::aid-bit2>3.
更新日期:2000-01-01 00:00:00
abstract::Cell morphology is an important macroscopic indicator of cellular physiology and is increasingly used as a mean of probing culture state in vitro. Phase contrast microscopy (PCM) is a valuable tool for observing live cells morphology over long periods of time with minimal culture artifact. Two general approaches are c...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26064
更新日期:2017-01-01 00:00:00
abstract::In view of the biochemical reaction catalyzed by enzyme powder suspended in a water-insoluble organic solvent, an equation was derived to estimate the amount of water bound to the enzyme powder. With this equation, an apparent adsorption isotherm between free water (water freely dissolved in benzene) and bound water (...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260340613
更新日期:1989-09-01 00:00:00
abstract::The biological molecule responsible for the suppression of pyritic sulfur in fine coal simulated froth flotation treated with bacteria was identified. Protein was found to be the most effective agent in pyrite suppression of the three cell components (protein, lipid, and carbohydrate) assayed. Coal recovery and ash re...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260330606
更新日期:1989-02-05 00:00:00
abstract::A mechanistic model of enzymatic hydrolysis taking into account the morphology of the cellulosic particles and its evolution with time was developed. The individual behavior of the main enzymes involved in the reaction (cellobiohydrolases, endoglucanases, and β-glucosidases), as well as synergy effects, were also incl...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25873
更新日期:2016-05-01 00:00:00
abstract::C-terminal lysine (C-K) variants are commonly observed in therapeutic monoclonal antibodies and recombinant proteins. Heterogeneity of C-K residues is believed to result from varying degree of proteolysis by endogenous carboxypeptidase(s) during cell culture production. The achievement of batch-to-batch culture perfor...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.24510
更新日期:2012-09-01 00:00:00