Showing papers on "Bioprocess published in 2002"

Bioprocess considerations for production of secondary metabolites by plant cell suspension cultures

Abstract: Plant cell culture provides a viable alternative over whole plant cultivation for the production of secondary metabolites. In order to successfully cultivate the plant cells at large scale, several engineering parameters such as, cell aggregation, mixing, aeration, and shear sensitivity are taken into account for selection of a suitable bioreactor. The media ingredients, their concentrations and the environmental factors are optimized for maximal synthesis of a desired metabolite. Increased productivity in a bioreactor can be achieved by selection of a proper cultivation strategy (batch, fed-batch, two-stageetc.), feeding of metabolic precursors and extraction of intracellular metabolites. Proper understanding and rigorous analysis of these parameters would pave the way towards the successful commercialization of plant cell bioprocesses.

Stabilizing plasmid copy number to improve recombinant protein production.

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, resulting in a loss of protein yield. Excessive plasmid replication is observed after inducing recombinant gene expression, which greatly contributes to metabolic overload of the host cell. The transcriptional and translational machineries are extremely overstrained. By abolishing sequence homology between ColE1 RNA I/RNA II and tRNAs, we were able to restore the plasmid's replication control mechanisms and to keep the plasmid copy number constant throughout the culture process, thereby prolonging metabolic activity and productivity of the bacterial expression system. Because the bacterial host cell is not being exploited beyond its tolerable potential with this method, the constancy of the plasmid copy number level throughout the whole period of the bioprocess provides novel strategies for bioprocess optimization.

In-situ-fluorescence-probes: a useful tool for non-invasive bioprocess monitoring.

Abstract: Optical sensors appear to be very promising for different applications in modern biotechnology. They offer the possibility to interface all the well known optical analysis techniques to bioprocesses via fiber optical cables. Thus, high sophisticated and sensitive optical analysis techniques can be coupled to a bioprocess via these light signal transporting fibers. A wide variety of sensor types for application in biotechnology has been described [1-4]. Normally these sensors are non-invasive and the response times are nearly instantaneous. In particular, the use of glass fiber technology makes these sensors small, robust and reduces their costs.

Online monitoring of a bioprocess based on a multi‐analyser system and multivariate statistical process modelling

Abstract: Multivariate statistical process control (MSPC) was for the first time applied to analyse data from a bioprocess on-line multi-analyser system consisting of an electronic nose (EN), a near-infrared spectroscope (NIRS), a mass spectrometer (MS) and standard bioreactor probes. One hundred and fifty sensor signals from the electronic nose, 1050 wavelength signals from the NIRS, carbon dioxide evolution rate calculated from mass spectrometer signals and standard bioreactor data (eg amount of substrate fed) were interrogated for their ability to model a bioprocess using MSPC. The models obtained were validated on a recombinant Escherichia coli fed-batch process for tryptophan production. Limiting trajectories were defined in the MSPC models for warning, action, and process experience with respect to biomass and tryptophan concentrations. The results showed the capacity and robustness of MSPC models for monitoring with multi-analysers and allowed a comparison of the different analysers' suitability for this kind of data processing. Furthermore, the results demonstrate that MSPC models provide a functional and versatile framework for coping with large information flows and are also suited to a variety of other bioprocessing monitoring and control tasks. © 2002 Society of Chemical Industry

An introduction to metabolic and cellular engineering

Abstract: Metabolic and Cellular Engineering in the Context of Bioprocess Engineering Systems Biology and the Complex Systems Approach Networks in Systems Biology Black and Grey Boxes: Levels of Description of Metabolic Behavior in Microorganisms Matter and Energy Balances Mass Balance as the Basis of Metabolic Flux Analysis Microbial Growth Under Steady and "Balanced" Conditions Metabolic Fluxes During Balanced and Steady State Growth Toward a Rational Design of Cells Metabolic Design of Cells as Catalysts Stoichiometry of Growth: the Equivalence Between Biochemical Stoichiometries and Physiological Parameters Metabolic Flux Analysis Applications The Transdisciplinary Approach as Applied to the Rational Design of Microorganisms Modeling Networks: Concepts and Tools Kinetic Modeling in Microbial Physiology and Energetics Metabolic Control Analysis of Networks Analysis and Detection of Complex Nonlinear Behavior in Networks Complex Qualitative Behavior in Networks Dynamic Aspects of Bioprocess Behavior Oscillatory Phenomena in Continuous Cultures Bioprocess Development with Plant Cells Plant Metabolism Carbon Assimilation, Partitioning, and Allocation in Higher Plants Cell Culture Techniques Metabolic and Cellular Engineering in the Industrial Production of Therapeutic Proteins Biological Complexity and Systems Bioengineering.

Metabolic engineering of animal cells

Abstract: Animal cells are widely used in industrial processes as sophisticated cell factories to obtain a high number of complex proteins with correct post-translation modifications and biological activity, with many applications in diagnostic and therapeutic uses. However, from the bioprocess point of view these are still sub-optimal processes, mainly due to the complex requirements for the in vitro growth of the cells, their metabolic and physiological patterns, and the response of mechanisms developed for in vivo growth to the external conditions found in culture in vitro. Metabolic engineering, combined with the corresponding redesign of the process itself, offers the possibility to the enhance the performance of animal cells grown in in vitro systems, targeting how to redesign the cells themselves to make them more robust, efficient, and productive. This paper reviews efforts made in this direction, and how the metabolic engineering of animal cells has been approached to reshape their profiles in various key aspects, namely: central metabolism, protection of apoptosis, regulation of cell cycle, and finally, the combined engineering of different aspects.

β‐Galactosidase, Enzymology

Abstract: Introduction Brief Survey of β-Galactosidase Enzymology Microbial Distribution and Purification Molecular Properties, Substrates, and Inhibitors Structural Classification Molecular Properties and Current Status in Bioprocess Technology of Some Microbial β-Galactosidases Fungal Enzymes Bacterial and Actinomycetous Enzymes Mechanism of the Escherichia coli lacZ β-Galactosidase-Catalyzed Reactions Kinetic Mechanism of Reactions with ONPG Kinetic Mechanism of Reactions with Lactose Role of Active Site Residues in Catalysis Applications of β-Galactosidase-Catalyzed Reactions in Bioprocess Technology Hydrolysis Application of Immobilized Enzyme Technology in Industrial Lactose Hydrolysis Production of Lactose-Related Oligosaccharides by Transgalactosylation Functional Properties of Lactose-Related Oligosaccharides Functional Modification of Various Compounds by Transgalactosylation Concluding Remarks Bibliography Keywords: functional modification of bioactive compounds; galactooligosaccharides; β-galactosidase; galactosyllactose; glycosylhydrolase family; lactase; lactose hydrolysis; microbial enzyme; transgalactosylation; reaction mechanism

Production of lovastatin examined by an integrated approach based on chemometrics and DOSY-NMR.

Abstract: Microbial secondary metabolites are one of the sources of therapeutic molecules in the pharmaceutical industry. Product quality and high yields of secondary metabolites are the main goals for the commercial success of a fermentation process. Our novel approach was based on the decision-tree algorithm to determine the key variables correlated with the process outcome and on DOSY-NMR to identify both co-metabolites and impurities, and it improves fermentation systems and speeds up bioprocess development. The approach has been validated in the case of lovastatin production from Aspergillus terreus. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 589–593, 2002.

Bioprocess for the generation of cells from spheroid-forming cells

Abstract: The present inventors identified aggregation of embryonic stem cells and embryoid bodies (EBs) as the cause of the difficulty in generating large numbers of the embryonic stem cells (ES) cell-derived tissues. To counter this, the invention provides a novel bioprocess where aggregation of spheroid forming cells, such as embryonic stem cells and spheroids, such as EBs is controlled, such as by encapsulation of within a matrix. As a result, EBs can be generated with high efficiency and cultured in high cell density, well-mixed systems. Well-mixed conditions facilitate measurement and control of the bulk media conditions and allow for the use of scalable bioreactor systems for clinical production of tissue. Therefore, the invention enables generation of ES cell-derived tissue on a clinical scale. The invention is also applicable to any spheroid-forming cells and other types of pluripotent cells.

Software agents for bioprocess monitoring and control

Abstract: We argue for the appropriateness of using software agents for the monitoring and control of bioprocesses. Different approaches to the design of individual agents as well as complete multi-agent systems are discussed. This is followed by a brief discussion of a number of successful agent-based monitoring and control applications from different domains. We conclude by discussing the advantages and disadvantages of agent technology for monitoring and control of bioprocesses. © 2002 Society of Chemical Industry

A bioprocess for the generation of cells derived from spheroid-forming cells

Abstract: The present inventors identified aggregation of embryonic stem cells and embryoid bodies (EBs) as the cause of the difficulty in generating large numbers of the embryonic stem cells (ES) cell-derived tissues To counter this, the invention provides a novel bioprocess where aggregation of spheroid-forming cells, such as embryonic stem cells and spheroids, such as EBs is controlled, such as by encapsulation of within a matrix As a result, EBs can be generated with high efficiency and cultured in high cell density, well-mixed systems Well-mixed conditions facilitate measurement and control of the bulk media conditions and allow for the use of scalable bioreactor systems for clinical production of tissue Therefore, the invention enables generation of ES cell-derived tissue on a clinical scale The invention is also applicable to any spheroid-forming cells and other types of pluripotent cells

A bioprocess for producing uniform embryoid bodies from embryonic stem cells in a high density bioreactor

Abstract: The present inventors identified aggregation of embryonic stem cells and embryoid bodies (EBs) as the cause of the difficulty in generating large numbers of the embryonic stem cells (ES) cell-derived tissues. To counter this, the invention provides a novel bioprocess where aggregation of spheroid-forming cells, such as embryonic stem cells and spheroids, such as EBs is controlled, such as by encapsulation of within a matrix. As a result, EBs can be generated with high efficiency and cultured in high cell density, well-mixed systems. Well-mixed conditions facilitate measurement and control of the bulk media conditions and allow for the use of scalable bioreactor systems for clinical production of tissue. Therefore, the invention enables generation of ES cell-derived tissue on a clinical scale. The invention is also applicable to any spheroid-forming cells and other types of pluripotent cells.

Fluorescence Techniques for Bioprocess Monitoring

Abstract: Introduction Principles of Single-Wavelength Fluorosensors Application of Single-Wavelength Fluorosensors New Developments in Fluorosensor Technology and Application Two-Dimensional Fluorescence Biogenic Fluorophors Instrumentation Hitachi F4500 Spectrofluorometer BioView Applications Bibliography Keywords: bioprocess monitoring; fluorescence; on-line; optical sensor

Modeling of the break process to improve tomato paste production quality : a thesis presented in partial fulfilment for the degree of Master of Engineering in Bioprocess at Massey University

Abstract: The pectic enzyme, Pectinmethylesterase (PE) and Polygalacturonase I and II (PGI and PGII), in the tomato fruit released after crushing during tomato processing reduce the viscosity of tomato paste by breaking down the insoluble pectin in the cell wall. To achieve higher viscosity tomato paste, the cold break (<60°C) or hot break (>60-95°C) processes can be used to inactivate the pectic enzyme and to achieve higher viscosity tomato paste. The study of tomato solids and PG enzyme activity showed that the levels of insoluble solids, total solids, pectin, and 0 Brix in Ferry Morse tomatoes were independent of fruit ripeness. The amount of PG enzymes was high in orange and dark red tomatoes and the activity of PG enzymes increased as a function of ripeness, from green to dark red . In the dark red tomato, the inactivation of PG enzyme activity was required to retain the level of pectin. Cold break temperatures below 60°C can not inactivate the PG enzyme activity. The PG enzymes started to be denatured when the hot break temperature was above 65°C and be completely destroyed when the break temperature was above 80°C. A mathematical model of the break process was formulated and Matlab programme was used to predict the effect of break temperatures on the pectin and PG enzyme concentration of the tomato pulp in the break tank for any inputs of feed rate (the flow rate to the break tank), feed ripeness, and residence time. The model was used to demonstrate the understanding and the optimisation of break process performance. Longer residence time of dark red tomato pulp in the break tank can decrease pectin fraction residual and increase enzyme inactivation in the tank temperature range 40 to 60°C. The pectin fraction remaining increased when the tank temperature was above 60°C because of the inactivation of PG enzymes. At 80°C there was no effect of residence time, the pectin fraction residual increased and reached 90% and enzyme fraction residual decreased to 10%. The effect of mixed tomato ripeness between the ripe fruit ( orange and dark red) with the unripe fruit (green, breaker, and turning), the level of PG enzymes in the break tank decreased and affected on the higher pectin fraction remaining. Lower break temperature can be therefore used in this process to inactivate the low amount of PG enzyme and to achieve the same extent of pectin hydrolysis. The interruption of the feed coming into the break tank during tomato processing can increase the pectin fraction remaining and the enzyme fraction remaining in a new steady state when the feed was turned on.

Miniature Bioprocess Array: A Platform for Quantitative Physiology and Bioprocess Optimization

Abstract: : We have developed a high-throughput miniature bioprocess array for the cultivation of microorganisms in a controlled, reproducible environment. The miniature bioprocess array is based on an array of 150-microliters wells, each one of which incorporates MEMS for the closed-loop control of cell culture parameters such as temperature, pH, and dissolved oxygen. The wells incorporate a suite of sensors, including interdigitated capacitors for cell density, thermopile temperature sensors, and oxygen sensors. Deep reactive-ion etched (DRIE) capacitive sensors enable new capabilities, such as the measurement of cell density in the bulk of the solution. Oxygen is generated by electrolysis, which also provides a means of mixing the solution in the well. Data acquisition, communication, and control will be implemented in foundry CMOS. A four-wire bus connects the electronic interface at each well to each other and to a battery, a clock serial input/output, and ground.

바이오필터의 공학적 해석

Abstract: 【Biofiltration is a bioprocess treating volatile organic compounds (VOCs) in order to convert the VOCs to harmless products. This review on biofiltration is intended to provide an engineering concept such as removal efficiency, maximum load, elimination capacity and so on. Besides, modeling concept of biofilter is also supplied for designing biofilter system. Quantitative data generated in our research group is shown to explain the engineering concept as well as the modeling idea.】

Pseudomonas, Process Applications

Abstract: Introduction Biosynthesis Biotransformations Redox Reactions Group Transfer Reactions Hydrolyzations Addition and Elimination Reactions Isomerizations Ligations Bioprocess Technology Toxicity of Apolar Organic Solvents Controlled Substrate Feed In Situ Product Extraction Outlook Bibliography Keywords: biocatalysis; bioconversion; bioprocesses; biotransformation; industrial processes; Pseudomonas