bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioreactors, Perfusion
Authors: Su Wei Wen 
Published: October 2009

Abstract
Perfusion culture entails continuous or semi‐continuous flow of a nutrient solution through a cell population while the cells are retained in the culture vessel. The main advantage of perfusion culture is its ability to achieve high cell density and allow convenient harvest of secreted products and/or removal of harmful extracellular metabolic byproducts. This oftentimes leads to improved volumetric productivity. In order to retain cells (and preferably viable cells) in a perfusion bioreactor, a key design element is the cell‐retention system. In this article, the current development of perfusion bioreactors for mammalian cell culture, with focus on the cell retention system, is reviewed.
Cell Growth and Protein Expression Kinetics
Authors: Kompala Dhinakar S. 
Published: October 2009

Abstract
Typical experimental data on the mammalian cell growth and protein expression kinetics in batch and continuous bioreactors are discussed with the focus on maximizing the protein production. Two strikingly different patterns of growth‐associated and inverse‐growth‐associated production kinetics observed in continuous bioreactors at steady state are discussed along with plausible mechanisms for explaining this difference such as the specific cell cycle phase‐dependent gene expression models. Unstructured kinetic models developed for kinetics of mammalian cell growth, substrate utilization, and protein expression are discussed to highlight the successes and failures of this modeling approach in simulating the dynamics of cell growth and production. Structured kinetic models, which are more detailed and hence capable of addressing the complex metabolism of mammalian cells, are introduced briefly along with their difficulty of estimating the values for the increasing number of model parameters.
Cell Immobilization: Engineering Aspects
Authors: Willaert Ronnie 
Published: October 2009

AbstractThe performance of immobilized cells is influenced by mass transport of substrates to the cells and of products from the cells to the bulk fluid, as well as the cell growth in the immobilization matrix. Both internal and external mass transfer limitations have to be considered in the design of immobilized cell systems. In this article, the various methods of measurement of the diffusion coefficient are reviewed. The influence of the presence and growth of living cells in the immobilization matrix on the diffusion coefficient is discussed. Internal diffusion in gel systems, microcapsules, and dense cell masses, that is biofilms, bioflocs, and mammalian cell aggregates is treated in detail, as well as internal mass transport by convection is considered. Finally, the mathematical modeling of reaction–diffusion systems of immobilized cells is discussed, with special attention to gel entrapment and microencapsulation.
Cell Products: Antibodies
Authors: Birch John R. 
Published: October 2009

Abstract

The applications of monoclonal antibodies are now widespread, as research tools, as
in vitro
diagnostic reagents and, increasingly, as
in vivo
diagnostic and therapeutic products. The number of antibody therapeutics on the market and in clinical trials has increased rapidly in recent years and global production has now reached tonnage quantities. Manufacturing technology is for the most part based on mammalian cell culture in fed‐batch suspension culture. Improvements in cell‐line construction and in media and feeds have led to dramatic improvements in productivity. Titers of grams per liter are now seen routinely and, increasingly, this is being achieved in media that are chemically defined and protein‐free. The requirement for very large quantities of antibody products also presents a challenge in terms of purification processes. Currently, purification is based on column chromatography, typically with a Protein‐A affinity step early in the process. In addition to optimizing processes for productivity, there is a growing awareness of the need to design cells and processes to deliver products with desired structural features.
Enhancement of Central Energy Metabolism, Microbial
Authors: Yokota Atsushi , Wada Masaru 
Published: October 2009

AbstractImproving the productivity of useful metabolites is critically important for industrializing the fermentation process. For this to be achieved, rapid conversion of the fermentation substrate into the target metabolite through enhancing central metabolism seems rational. Since the discovery of “Pasteur effects” more than 100 years ago, scientific evidence has accumulated, especially in the past 50 years, that central metabolism is under the control of the energy status of cellsin vivoin such a way that catabolism is enhanced under energy‐deficient conditions. We investigated enhancement of fermentative production by boosting central metabolism through the manipulation of energy metabolism. We found that the introduction of defective F1Fo‐ATP synthase to impair oxidative phosphorylation is effective for enhancement of pyruvate production inEscherichia coliK‐12 (hereafter, we collectively define this mutation as the “atpmutation” since F1Fo‐ATP synthase is encoded by theatpoperon inE.coliK‐12). Clarification of the physiological alterations associated with theatpmutation revealed several interesting metabolic changes. Excellent producers of pyruvate and acetate have recently been engineered inE.coliK‐12, in which theatpmutation appears to contribute markedly to increase glucose consumption and metabolite production of the producers. Furthermore, theatpmutation was found to be effective for a gram‐positive industrially important bacterium,Corynebacterium glutamicum, in enhancing both glucose consumption and glutamic acid production. Elucidation of metabolic alterations in thisatpmutant revealed significant differences from those found in theE.coli atpmutant, suggesting a diversity of adaptive responses to energy deficiency in different bacterial species.
Conifers: Culture and Genetic Engineering
Authors: Bonga Jan M. , Von Aderkas Patrick , Klimaszewska Krystyna 
Published: October 2009

AbstractConifer biotechnology has advanced greatly in the last couple of decades. Even though much of the field is still experimental, improvements in somatic embryogenesis and cryopreservation protocols have resulted in the production of genetically improved planting stock for reforestation. This technology has been most effective for some of the spruce, pine, andLarixspecies as well as for Douglas fir. Other conifer species have been less responsive, and effective application procedures remain to be established. Genetic engineering is still largely confined to the experimental and field‐testing stage, but applications in the field of pathogen and pest resistance and some other features can be expected in the near future.
Biocatalysis: Database Tools
Authors: Wackett Lawrence P. , Ellis Lynda B.M. 
Published: October 2009

AbstractIndustrial biotechnology increasingly depends on the use of enzymes to carry out desired biotransformation reactions. The reactions have traditionally been used to produce specialty chemicals. Now, enzymic catalysis is being used to manufacture commodity chemicals and fuels. Thousands of enzymes are available commercially; millions are produced by microorganisms in nature. Applications of enzyme catalysis are based on using the best enzyme and optimizing metabolic pathways. Databases are crucial to this effort. Enzyme databases contain information on enzyme characteristics and substrate specificity. Gene sequence databases provide information crucial for cloning and expressing key enzymes. Metabolism databases reveal how enzymes interact in specific organisms to catalyze consecutive reactions. Microorganism databases provide information about the history and availability of individual strains. Chemical substance databases provide key compound information; solubility, reactivity, and biological activity. Commodity‐scale chemical substances that are substrates for industrial enzymes include sugars (glucose isomerase), sugar polymers (cellulase), nitriles (nitrile hydratase and nitrilase), proteins (rennin), and β‐lactam antibiotics (penicillin acylase). Databases will play a prominent role in synthetic biology, using biological tools to engineer novel enzymes and metabolic pathways for industrial biotechnology.
Dehydrogenase
Authors: Sánchez Antoni , Barrena Raquel 
Published: October 2009

Abstract

Dehydrogenase
is a general term describing a wide subgroup of oxidoreductases, enzymes that participate in reactions involving electron transfer. Because electron transfer implies the presence of an electron donor and an electron acceptor, and the chemical typology of these substances can be very different, the dehydrogenase class includes a large number of enzymes.

Dehydrogenases are produced by a large number of microorganisms and other living organisms. Numerous applications have been described for them, the most advanced being their use in chiral resolution after some immobilization procedure. Also, interest in using dehydrogenase activity to monitor the global aerobic activity in environmental biotechnology has grown in recent years. In this application, dehydrogenase activity is used to monitor the biodegradation process, as it is related to the metabolic reactions producing energy in the form of ATP through the oxidation of organic compounds. It has been successfully applied to the biological treatment of wastewater and solid wastes and soil bioremediation.

Specific dehydrogenase activity can be determined by a typical enzyme substrate–specific reaction. Nevertheless, values of overall dehydrogenase activity are also important because this value can often be related to the aerobic activity in ill‐defined (unsorted) media. In this case, two main substrates are typically used to accept electrons from dehydrogenase enzymes, triphenyl‐tetrazolium chloride (TTC) and 2‐(
p
‐iodophenyl)‐3(
p
‐nitrophenyl)‐5‐phenyl tetrazolium chloride (INT); the resulting reduced products are forms of red‐colored formazan (TPF and INTF, respectively).
Drying: Biological Materials
Authors: Law Chung Lim , Mujumdar Arun S. 
Published: October 2009

AbstractNew advancements in biotechnology has made many biotechnological products such as yeast, bacteria, vitamins, enzymes, proteins, carbohydrates, antibiotics, fungi, lysine, blood, plasma, realize in industry and commercial market. Most of these products appear in the form of liquid, suspension, or paste, which require refrigeration for storage. Refrigeration however limits the widespread application of the products mentioned above, as the operating costs and handling of frozen products is high and difficult. As such, dehydration and drying can be deployed to reduce the handling cost, while prolonging the shelf life, retaining the active ingredients activity, maintaining the cell survival and vitality, as well as its physical, textural, sensory, and optical properties. Biotechnological products are heat sensitive. Conventional drying methods for nonbiotechnological products such as hot air drying may damage and denature the product, destroy the cell and active ingredients, cause case hardening and browning. Over the years, freeze‐drying is the most common method used in the drying of some of the biotechnological products mentioned above. However, the operating cost and the drying time of freeze‐drying are comparatively high. As oil prices are skyrocketing and there is no sign that the price will ease in the near future, researchers and scientists have designed, tested, and improved various drying methods in order to improve drying efficiency and performance. This article discusses various conventional drying methods, which are common to the drying of biotechnological products, and describes various advanced drying technologies that give improvements and better performance with reference to drying strategy, drying medium, handling of drying materials, and mode of heat input. These include intermittent drying, pulse combustion drying, impinging stream drying, cyclic pressure vacuum drying, spray‐freeze‐drying, atmospheric freeze‐drying, vacuum fluidized bed drying, low‐pressure spray drying, superheated steam drying, heat pump drying, inert medium drying, supercritical fluid drying, sorption drying, spouted bed drying, jet spouted bed drying, vibrating fluidized bed drying, pulse fluidized bed drying, high electric field drying, and microwave drying. Recent research findings of these drying technologies are given as well.
Enzymatic Transglycosylation
Authors: Tramice Annabella , Andreotti Giuseppina , Giordano Assunta , Trincone Antonio 
Published: October 2009

AbstractThe most important functions of carbohydrates are structural roles and energy storage, but carbohydrate parts of glycoproteins and glycolipids are involved in biological functions mainly related to cell recognition events. Carbohydrates are also important molecules in the technological domain. A copious amount of information concerning the synthesis and transformation of complex saccharides in living organisms exists nowadays: the enzymes responsible for the synthesis of glycosidic linkage have been recognized as glycosyltransferases. Glycoside hydrolases (glycosidases) are different enzymes responsible for the hydrolysis of glycosidic linkages, but they can be efficiently used in synthesis. Indeed, at the present time, genetic engineering of glycosidases has emerged as a powerful tool for scientists, in the synthetic field, with the aim to set up chemically, efficient biocatalysts. In this contribution, the glycosyl transfer between oxygen nucleophiles will be analyzed from the chemical and the biotechnological points of view. Chemical machinery for hydrolysis and synthesis of the enzyme glycoside hydrolases and glycosyltransferases will be analyzed, including issues inherent to donors and acceptors and biocatalyst natural sources; in particular, discussing the modern genetic efforts to prepare tailored enzymes with high synthetic ability. Case studies for laboratory and industrial importance are analyzed as well.
Erythromycins
Authors: Minas Wolfgang 
Published: October 2009

AbstractFor well over 50 years the macrolide antibiotic erythromycin is in clinical use, and even today, macrolides hold a 20% share of the antibiotics market. The broad spectrum and the oral availability of macrolides have contributed to their success. The development of semisynthetic derivatives has greatly improved the clinical value of erythromycin and its derivatives. This article will provide an overview on erythromycin, its discovery, and biosynthesis, and on the development of semisynthetic derivatives. The macrolide's mode of action on the bacterial ribosome inhibiting the protein biosynthesis as well as the development of bacterial resistance is detailed. The clinical relevance of erythromycins, in particular of the latest developments, is emphasized.
Ethanol Fuel Production: Yeast Processes
Authors: Ingledew W.M. 
Published: October 2009

AbstractThe fuel alcohol industry has undertaken phenomenal growth since its rebirth in the 1980s. Since that time, it has developed with little industry‐wide appreciation of its size and strength, and the transformation of its science in order to lower production costs and to save energy and water. This short paper is designed to outline the steps of production in both wet milling and dry grind plants, provide a window on the new technologies that are proposed and utilized, demonstrate the size of the industry, the current energy balance in the process, the possibility of cellulose substrates augmenting starch‐based ethanol production, and provide a glimpse of the future of the industry.
Ethical Issues in Animal and Plant Cell Technology
Authors: Spier Raymond E. 
Published: October 2009

AbstractFollowing a definition of ethics and the different ethical systems that are commonly referred to, the ways by which differences in ethical positions might be resolved are presented. These principles are then used in subsequent sections to examine in some detail the ethical issues that are raised when animal and plant cells are used in the context of biotechnology. While such subjects relating to enzymes and hormones are covered, emphasis is given to the viral products of animal cells and to the vaccines that are made to prevent disease. The use of animal cells to replace animals in test systems is also examined. Contemporary issues of regulation and biodefence bring together technology and ethics and show that we have the means for advances in these areas but only if we are mindful of the ethical issues and are prepared with arguments to meet possible objections. It is helpful in such deliberations to consider the panoply of capabilities in these areas as tools and to recognize that the regulation of tool use is dependent on the intentionality of the tool user as is the case for all the tools that are available with us.
Microorganisms: Extremely Thermophilic
Authors: Gray Steven R. , Adams Michael W.W. , Kelly* Robert M. 
Published: October 2009

AbstractExtremely thermophilic microorganisms (Topt≥ 70°C) are found in geographically diverse marine and terrestrial environments and represent a wide range of growth physiologies. Extreme thermophiles thrive at high temperatures and, as such, different approaches must be taken to cultivate them in laboratory settings. Genome sequences of many extreme thermophiles have been completed and offer a glimpse into the basis for their high temperature life styles. A number of biotechnological applications have been envisioned that take strategic advantage of their thermophilicity, including the production of biohydrogen and recovery of base and precious metals from ores. As genetic systems are developed and implemented for extreme thermophiles, metabolic engineering approaches will be possible to tune the unique characteristics of these microorganisms for bioprocessing uses.
Flow Cytometry
Authors: Müller Susann , Bley Thomas 
Published: October 2009

AbstractMicroorganisms are widely used in biotechnology and present a wide biodiversity including yeast, algae, protozoa and bacteria. Because of their high abundances, and their large variety of metabolic activities which makes them ubiquitous, microorganisms represent a key component in environmental and biotechnical studies and applications. To enhance our understanding of the heterogeneity and complexity of the microbial consortia, both in term of composition and functioning, their direct analysis must be done on a single cell level and requires a non‐invasive interrogation of the cells. The developments of analytical flow and static cytometry, together with advances in the field of fluorescent probes have enabled the measurement of a wide range of cell characteristics. The study of technical systems where microbial cells interact within an artificially engineered environment (e.g. fermentation, bio‐remediation, bio‐transformation) is important for the biotechnical industry. Accurate measurements relating to cell proliferation, viability and scatter properties of cells are essential if informed decisions about a process are to be made. In this way, products can be harvested at optimal concentrations and inducible systems can be activated at the appropriate time so that high product yields are achieved. In the review are highlighted newly developed techniques and recent advances in this field.
Cephalosporin Production by Fungal Metabolic Engineering
Authors: Rodríguez‐Sáiz Marta , Fuente Juan Luis De La , Barredo José Luis 
Published: October 2009

AbstractMetabolic engineering is being used in optimization of β‐lactam production as a rational alternative to classical strain improvement programs, as well as for the construction of new biosynthetic pathways. Several examples on how metabolic engineering can be applied toAcremonium chrysogenumto enhance cephalosporin C production are described, including the overexpression ofcefEF,cefG,mecB, andcefTgenes. Additionally, an overview on the metabolic engineering of the β‐lactam biosynthetic pathways of the fungiA. chrysogenumandPenicillium chrysogenumto develop new biotechnological methods for the production of the commercially valuable cephalosporins 7‐aminocephalosporanic acid (7‐ACA) and 7‐aminodeacetoxycephalosporanic acid (7‐ADCA) is presented. Finally, recent developments on the direct evolution of the central enzyme of the cephalosporin biosynthetic pathway (deacetoxycephalosporin C synthase; DAOCS) as a key to the replacement of chemical processes to obtain 7‐ACA and 7‐ADCA are shown.
Gene Expression: Human Cells
Authors: Cacciuttolo Marco A. , Lee Gene , Chon John , Lewis John 
Published: October 2009

Abstract
Human cell lines are becoming increasingly attractive for the expression of proteins in both research and commercial production of human therapeutics. Most of the recent interest derives not only from the recent achievements in record levels of protein expression but also from the record of safety of using human cells as substrates to date, and also from advances in the techniques and methods used to express genes. In addition, human cells can offer a safer alternative for the production of human therapeutics; the majority of them being produced currently from nonhuman cell lines, which in some cases carry animal‐derived structures that have been shown to be harmful to humans. This article provides a succinct view of the current technology, safety, and regulatory aspects of using human cells for gene expression, including examples of industrial applications of human cell lines expressing recombinant proteins.
Protein Glycosylation: Methods for Determination
Authors: Butler Michael , Perreault Helene 
Published: October 2009

Abstract
Glycoproteins are produced in eukaryotes as pools of different glycoforms with varying glycan structures attached to a single invariant peptide backbone. The characteristic glycoform profile is dependent upon the glycan structures added during co‐translation and modified post‐translationally. The glycosylation process is important to ensure the full efficacy of any glycoproteins used therapeutically.
As the number of therapeutic increases there is a requirement to apply rapid analysis of glycans to glycoproteins that are produced as biopharmaceuticals for human therapy. Such methods are required as quality control to ensure that there is minimal variability between multiple batches in a bioprocess. Similarly, protocols adopted for diagnostic screening need to be rapid in order to handle multiple samples.
Full structural analysis is possible by a combination of techniques including NMR, mass spectrometry and HPLC using exoglycosidase arrays for sequential breakdown of glycan structures. However there are other techniques that allow rapid screening that do not necessarily include full structural analysis. High though‐ put techniques are available for mass spectrometry, HPLC as well as lectin arrays, FACE or capillary electrophoresis Rapid analysis using such techniques may provide profiles that are adequate at least for ensuring consistency in production.
The choice of method therefore will depend upon the degree of analytical information required.
Several of the methods described in this chapter may be acceptable as providing glycan profiles but may not provide unambiguous structural assignments.
The analysis of glycosylation patters are important to ensure consistency during a biopharmaceutical production process. Here we present the basis for analysis by several techniques that might be suitable during bioprocessing.