bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chiral Alcohols by Enzymatic Preparation
Authors: Borup Birthe , Daussmann Thomas , Collier Steve 
Published: April 2010

AbstractBiocatalytic processes are of increasing importance in the production of chiral alcohols which are important building blocks in the synthesis of chemical catalysts, liquid crystals, agrochemicals and pharmaceuticals. Methods for the synthesis of chiral alcohols can be subdivided into three general classes: traditional (such as classic racemic resolution, chromatography, chiral pool synthesis), asymmetric chemical, and biological (enzymes, whole microbial cells) methods. The last can also be applied to the more traditional methods. Enzymatic techniques are attracting a growing interest as green catalysts because of the different advantages they offer, as compared to other methods: high selectivity, high product purity, mild reaction conditions, competitive production costs, and excellent catalyst availability.In this contribution we give an overview of the biocatalytic approaches for the manufacture of chiral alcohols. To our knowledge there are currently about five major enzyme groups applied for the synthesis of chiral alcohols. The first one reduces carbonyl functional groups (ketones) to enantiopure secondary alcohols (dehydrogenases or reductases). The second group forms alcohols by introduction of molecular oxygen with concomitant one or two electron reduction (mono‐ and dioxygenases). The third group forms alcohols by addition of water to unsaturated carbon carbon double bonds (hydratases) whereas the fourth one forms alcohols by nucleophilic addition of small molecules such as HCN at carbonyl groups which usually also results in a new C–C bond formation (hydroxynitrile lyases and aldolases). The last major group of enzymes discussed herein belongs to the traditional methods mentioned above and resolves racemic chiral alcohols by reacting with only one enantiomer in a racemic mixture (hydrolases).In a selection of case studies we demonstrate the high level of importance that biocatalytic processes have already gained in the industrial manufacture of chiral alcohols. There are numerous processes available that have been or still are operated in multi‐tonne scale. By solving the drawback of cofactor requirements and regeneration for a range of enzymes, especially in the area of asymmetric reduction, the dehydrogenases and oxygenases are now commonly used for commercial processes and are in several cases superior to whole‐cell microbial processes.The highly competitive nature of enzymatic processes compared to whole‐cell (fermentation) and chemical approaches is demonstrated with the example of the manufacture of optically active ethyl (R)‐3‐hydroxybutyrate.
Chromatography, Hydrophobic Interaction
Authors: Kårsnäs Per 
Published: April 2010

AbstractHydrophobic interaction chromatography (HIC) is based on complex interactions between the separation media and biomolecules. This compexity is due to that the salt‐mediated mechanism for attraction in unusually dependent also on the individual sterical structures of the counterparts. A hydrophobic ligand thus may express different separation selectivitiy patterns when coupled to different media with different tecniques. Prediction of results therefore cannot be made based on experiments performed on another separation medium with the same ligand. HIC uses moderately hydrophobic ligands where the molecules to be separated are forced to attach to the columns by increasing the ionic strength of the eluent. It is mainly used for large biomolecules forming multipoint attraction with the medium. Elution is performed with gradients of decreasing ionic strength and short and wide columns are used to optimize the separation. Tertiary structures tend to be preserved but attached molecules should be eluted as soon as possible due to the risc of confomational changes and enhanced binding making elution difficult. An HIC medium may be characterized by the profile of elution data of a set of marker proteins using PCA making possible the comparision and classification of media and prediction of results. Optimization is facilitated by running the sample through columns eqilibrated with stepwise higher ionic strength.
Clean‐in‐Place (CIP)
Authors: Bremer Phil J. , Seale Richard Brent 
Published: April 2010

AbstractClean‐in‐place (CIP) is the cleaning of the assembled plant (vats, fermenters, tanks, processing equipment, probes) and pipeline circuits (values, flowmeters, gaskets) by the jetting or spraying of surfaces or the circulation of cleaning solutions under conditions of high temperature, turbulence and flow velocity. CIP involves little or no manual involvement from an operator. Cleaning efficiency is associated with mechanical, thermal, and chemical activity. Important factors influencing the effectiveness of the CIP include the nature of the material to be removed, the design of the plant and CIP system, the type of surface requiring cleaning, the concentration and nature of the cleaning solution, and the temperature and duration of the cleaning stages [1]. Compared to manual cleaning regimes, a well‐designed, validated, operated, and monitored CIP system will dramatically increase cleaning effectiveness and reproducibility, reduce costs, and enhance operator safety.
Cyclotides
Authors: Dörnenburg Heike , Craik David J. 
Published: April 2010

Abstract
The cyclotides are a recently discovered family of miniproteins that contain a head‐to‐tail cyclized backbone and a knotted arrangement of disulfide bonds. They are approximately 30 amino acids in size and are present in high abundance in plants from the Rubiaceae, Violaceae, and Cucurbitaceae families, with individual plants containing a suite of up to 100 cyclotides. They have a diverse range of bioactivities, including uterotonic, anti‐HIV, antitumor, and antimicrobial activities, although their natural function is believed to be in host defence against pests and pathogens. In addition to their natural activities, cyclotides have been proposed as a stable peptide template for applications in protein engineering and drug design. Their exceptional stability and resistance to thermal, chemical or enzymatic treatments can be attributed to the cyclic cystine knot structural motif that forms their compact molecular core. The backbone loops protruding from this core vary in their amino acid compositions and because of this tolerance to substitutions, cyclotides can be regarded as a natural combinatorial template. To date, most bioactivity studies on cyclotides have involved peptides extracted from plants. Cyclotides are amenable to chemical synthesis but this is expensive and so the development of bioprocesses for the production of cyclotides is an important objective for enabling their future industrial applications. This article gives a brief overview of the structures and properties of cyclotides and discusses new approaches to their production using bioprocesses on an industrial scale.
Scale‐Up of Chemical and Biotechnological Processes
Authors: Zlokarnik Marko 
Published: April 2010

AbstractThe article deals, first of all, with dimensional analysis; a method by which a complete set of parameters that fully describe a process under consideration is transformed to a set of dimensionless numbers (pi numbers). On the one hand, the application of this method leads to an essential compression of the scope which describes the process. On the other hand, the produced dimensionless products are scale invariant with respect to each dimension, therefore also to the dimension of length, which is the basis for a reliable scale‐up.The scale‐up requires a threefold similarity: a geometrical, a material, and a process‐related one. The material similarity may cause problems if non‐Newtonian fluids (pseudoplastic and/or viscoelastic) are involved. This problem is comprehensively discussed in the second part of the article.The third part is concerned with some important procedures relating to mechanical and thermal process engineering, which are often applied in biotechnology. Examples are given of how scale‐up may be used in such cases.
Enzyme‐Catalyzed Reactions in Ionic Liquids
Authors: Gorke Johnathan , Srienc Friedrich , Kazlauskas Romas 
Published: April 2010

Abstract

Ionic liquids, also called molten salts, are mixtures of cations and anions that melt below 100°C. Typical ionic liquids are dialkylimidazolium cations with weakly coordinating anions such as [BF
4
] or [PF
6
]. Deep eutectic solvents are also included in this review because their properties are similar. Deep eutectic solvents are mixtures of salts such as choline chloride and uncharged hydrogen bond donors such as urea, oxalic acid, or glycerol. The advantage of using ionic liquids is enhanced solubility of substrates or products without inactivation of the enzymes. Ionic liquids as cosolvents with water help to dissolve nonpolar substrates, but do not inactivate enzymes like water‐miscible organic solvents do. The enhanced solubility of substrates usually increases the rate of reaction and often increases the regio‐ or enantio‐selectivity. Ionic liquids can also serve as solvents for nonaqueous reactions. In these cases, they are especially suitable for dissolving polar substrates. Polar organic solvent alternatives inactivate enzymes but ionic liquids do not, even when they have similar polarities. Hydrolases and oxidoreductases are particularly well‐studied in ionic liquids. Besides their solubility properties, ionic liquids and deep eutectic solvents may be greener than organic solvents because ionic liquids are nonvolatile and can be made from nontoxic components.
Enzymatic C‐C Bond Formation, Asymmetric
Authors: Kara Selin , Liese Andreas 
Published: April 2010

AbstractThe environmental awareness has grown during the past years focusing on efficient utilization of energy, elimination of waste and avoidance of toxic and/or hazardous reagents.Biocatalysis fulfills the requirement of “green chemistry”; since enzymes are biodegradable catalysts which can effectively catalyze the reactions under mild conditions(ambient temperature, no need for high pressure, no extreme pH, no toxic solvents and no heavy metal catalysts).C–C bond formation reactions are fundamental to all of organic chemistry, and enzymes show promise for use in this field. A variety of versatile building blocks in organic and pharmaceutical chemistry can be synthesized by biocatalysts. In comparison to available chemical routes enzymes also provide chemo‐, regio‐, and stereoselective catalysis. Different enzyme classes are applied in the field of C–C bond formation to synthesize complex, aldol reactions, and cyanohydrin formations. Few applications are also found in ketol‐ and aldol transfer reactions. Furthermore, promiscuous activity of lipases can be applied in C–C bond formation reactions.
Enzyme Immobilization, Biocatalyst Featured with Nanoscale Structure
Authors: Fei Gao , Ma Guang‐Hui , Wang Ping , Su Zhi‐Guo 
Published: April 2010

Abstract
Since the industrialization of heterogeneous biocatalysts in the 1960s, substantial research efforts have been taken to construct feasible biocatalyses. The surprising progresses of nanotechnology in the 1990s were soon closely followed by the rapid development of nano‐biotechnology. Quite a number of advanced nanomaterials have shown great potential in revolutionizing the preparation of biocatalysts. Mesoporous carriers, one of the most recent, intensively studied materials, could provide a highly ordered internal space with size comparable to enzyme molecules, a considerable loading capacity, and enzyme stability. The large curvature of nanoparticles would benefit the conformational stability, and the Brownian motion of nanobiocatalysts such as the solution behavior nanoparticles, tethered and gel‐armored enzymes, would improve the mass transportation when compared to the traditional heterogeneous catalysis. Some other nanomaterials, such as nanofibers and nanotubes have shown potential for revolutionizing the enzyme support and industrial bioprocesses. More sophisticated hierarchical structure based on nanobiocatalysts is also discussed in this article; this was developed to overcome the drawbacks and ensure sustainable development of nanobiocatalysts.
Freeze‐Drying, Pharmaceuticals
Authors: Liu Jinsong 
Published: April 2010

AbstractThis article provides an overview of the fundamental aspects for pharmaceutical freeze‐drying, including the rationale for freeze‐drying process design and control, the basics of formulation development for freeze‐drying, the importance of the container‐closure system, and a general description of pharmaceutical freeze‐dryers. In the second part of this article, the challenges in freeze‐drying scale‐up and transfer, freezing control, use of cosolvent, freeze‐drying in syringes, process analytical technology, and quality‐by‐design in freeze‐drying have been discussed, and some new advancements related to these aspects are also highlighted.
Glyoxylate Bypass ofEscherichia Coli, Regulation
Authors: Laporte David 
Published: April 2010

AbstractThe glyocylate bypass of E. coli has served as a model system for the regulation of metabolism. This pathway, which is essential for growth on acetate, is regulated my multiple mechanism, including protein phosphorylation, allosteric interactions and transcriptional regulation. By studying this system, the fundamental principles of metabolic regulation can be elucidated.
Inoculum Expansion Methods, Recombinant Mammalian Cell Lines
Authors: Kloth Claudia , Maclsaac Glenn , Ghebremariam Haile , Arunakumari Alahari 
Published: April 2010

AbstractThis article reviews general practices and state‐of‐the‐art inoculum expansion methods for recombinant mammalian cell lines. Suspension cell lines are the main focus due to their predominant current and anticipated future usage in large scale biomanufacturing. Conventional inoculum expansion methods are discussed including small scale flasks and seed bioreactors. Disposable technologies and approaches for time reduction during this incoulum expansion step are reviewed, as it is typically a time consuming phase of large scale manufacturing. Technology transfer and the influence of cell bank quality on successful vial thaw and expansion are alo addressed.
Laccase
Authors: Claus Harald , Strong Peter J. 
Published: April 2010

AbstractLaccases [EC 1.10.3.2, para‐bezenediol:dioxygen oxidoreductases] are multi‐copper proteins that oxidize various aromatic and non‐aromatic compounds by a radical‐catalyzed reaction mechanism using molecular oxygen as the secondary substrate. Laccase has a number of biological roles that include lignification, delignification, turnover of humic substances in soil and aquatic environments, pathogenicity, detoxification, morphogenesis, sporulation, growth and development of rhizomorphs, polymerization of melanin precursors and spore coat resistance. The ability of laccase to catalyze oxidation with only oxygen as a secondary substrate, its broad substrate range, and high catalytic constants have made it an appealing enzyme for a variety of remediative applications. These include bioremediation of phenolic‐rich wastewaters generated by paper and pulp, textile and dye, food and distillery industries as well as bioremediation of soils contaminated with recalcitrant xenobiotics such as chlorinated phenolic compounds, polycyclic aromatic hydrocarbons, explosives, endocrine‐disrupting chemicals, insecticides, fungicides, and herbicides. The enzyme's broad substrate spectrum, the use of readily available oxygen as the final electron acceptor, and no requirement for cofactors or peroxide have made it appealing for a variety of industrial applications in fields ranging from textile dyes, pulp and paper, biosensors, biofuel cells, chemical synthesis, beverage stabilisation, food products, and ethanol production. The advantages of laccase compared to other enzymes include relatively high yields, uncomplicated isolation from bulk fungal cultures, easy screening for specific producers with a broad substrate spectrum, a high degree of stability and activity especially after immobilization, and heterologous expression systems that have already been established. The characteristics of laccase allow for its potential utilization across a number of research areas, which will result in continued intensive investigations to better understand the enzyme and apply it forthe benefit of both humans and the environment.
Lipases
Authors: Kanwar Shamsher S. , Verma Madan Lal 
Published: April 2010

AbstractBioengineering is seen as a promising technique for yielding products by exploiting the concept of green chemistry. Amongst various enzymes available from diverse microbial and other sources, lipase is most versatile as it is endowed with the property of performing biochemical reaction in aqueous as well as organic/water‐restricted solvents. Microbial lipases have been expressed in efficient expression vectors to enhance their yields for commercial applications. However, to perform productive and efficient catalysis, involvement of principles of structural engineering of the biocatalyst, reaction conditions and choice of solvents is essential to achieve a higher rate of catalysis. The review revolves around the use of principles of bioengineering to subtly exploit inherent properties of lipases.
Amino Acids, Branched Chain,L‐Isoleucine
Authors: Jojima Toru , Inui Masayuki , Yukawa Hideaki 
Published: April 2010

AbstractThis article is an overview of the biosynthetic pathway ofL‐isoleucine and its regulation inEscherichia coli, and also describes evolution ofL‐isoleucine‐hyperproducing strains of microorganisms.L‐isoleucine is one of threebranched‐chain amino acids(BCAAs). They are synthesizedde novoby bacteria, fungi and plants, but are nutritionally essential for vertebrates. The importance ofL‐isoleucine in nutrition has stimulated intensive researches for development of microorganisms capable of overproducingL‐isoleucine for industrial production by fermentation from sugar. BCAAs are synthesized via parallel biosynthetic pathways. Four enzymes,acetohydroxyacid synthase(AHAS),acetohydroxyacid isomeroreductase(AHAIR),dihydroxy acid dehydrase(DH), andtransaminase B(TrB), are shared in bothL‐isoleucine andL‐valine synthesis. The first enzyme AHAS catalyzes the condensation of pyruvate and 2‐ketobutyrate forL‐isoleucine synthesis or the condensation of two molecules of pyruvate forL‐valine synthesis. Biosynthesis ofL‐isoleucine as well as other BCAAs is tightly controlled by complex regulation mechanisms that include multivalent regulation of both gene expression and feed back inhibition of enzyme activities by end product BCAAs. A variety of microbial strains with high productivity ofL‐isoleucine have been developed by screening mutants that can grow in the presence of BCAA analogs and by genetic engineering. In these mutants, the regulation ofL‐isoleucine synthesis including repression of gene expression and feed back inhibition are released. This article also describes a novel bioprocess,living cell reaction(LCR) process, that has potential to address the disadvantages of existing fermentation processes including low yield and by‐product formation.
Luminescent Materials, Biological Applications
Authors: Ronda Cees , Bachmann P. K. , Hummel H. , Juestel T. , Meriikhi J. 
Published: April 2010

AbstractThis chapter deals with inorganic luminescent materials and consists of two parts. It starts with a general description of luminescence‐ and excitation mechanisms, by giving a description of the way they operate in well‐known devices, like lamps or medical imaging equipment. In the second part, we concentrate on emerging medical applications. The focus is on the interplay between the performance of the luminophores required by the application and material properties of the luminescent compounds.
Protein Chromatography, Manufacturing Scale
Authors: Bertolini Joseph 
Published: April 2010

Abstract
Chromatographic procedures are an important part of many biopharmaceutical manufacturing processes for the purification of therapeutic proteins. The scale‐up of developed chromatographic processes from laboratory to pilot scale and finally. manufacturing scale can be achieved technically via well‐recognized principles involving increasing column surface area, while maintaining constant bed height, linear flow, and proportionally increasing the volume of solutions used in the process. Alternatively, one can ensure that the residence time of the protein during passage through the chromatographic resin is maintained during scale‐up. The integrity of the column packing at all scales is confirmed by the determination of the height equivalent to a theoretical plate (HETP) and the asymmetry factor from test chromatograms.
Microalgae, Mass Culture Methods
Authors: Grima Emilio Molina , Fernández Sevilla Jose María , Acién Fernández Francisco Gabriel 
Published: April 2010

AbstractThis chapter reviews the major factors governing the production of microalgae. Special emphasis is given to the impact of light availability, and its modification as a consequence of fluid‐dynamics within the photobioreactor (PBR), the mass‐liquid‐mass transfer and the heat‐transfer capacity of the PBR. The major types of bioreactors used for mass culture of microalgae, not only on the basis of a commercial application but also from an engineering point of view, are also reviewed. Equations for designing PBRs as a function of the operational variables are given. The biomass productivities obtained during an annual cycle in an industrial size tubular PBR built according to the proposed methodology are presented, both as experimental measurements and as model predictions. The solar efficiency of microalgal cultures is also analyzed, and the phenomena limiting it are discussed. Finally, some considerations about the management and operation of industrial scale cultures of microalgae are given.
Microbial Metabolite Export
Authors: Eggeling Lothar 
Published: April 2010

AbstractMicrobial metabolite export is an essential issue in industrial biotechnology. The reason is simple: otherwise, the development of advanced engineered strains might fail. Export belongs to the entire reaction sequence of substrate uptake and conversion to the valuable product finally accumulating in the medium. The relevance of export is probably best studied in the case of amino acid production withEscherichia coliorCorynebacterium glutamicumwhere specific exporters, when deleted, prevent amino acid production, or when overexpressed, increase amino acid production. However, antibiotic production also relies on exporters as the final step in cellular synthesis of these important metabolites. Another area where the importance of exporters is assessed is the use of whole cells for bioconversions occurring in organic solvents. This review covers these areas, gives a tabular overview on exporters recognized in biotechnology and describes also the varied methodology of exporter identification.
Cell Disruption, Microbial, Micromechanical Properties
Authors: Kampen Ingo , Kwade Arno 
Published: April 2010

AbstractIn the production of intracellular products, a cell disruption step in the downstream processing is necessary for product release. While in the past, cell disruption behavior was simply measured with different devices, today the microprocess within these devices is the focus of interest. This contribution summarizes current results of microbial micromechanical properties and briefly discusses the methods used for measurements. The industrially relevant cell disruption devices in a high pressure homogenizer, stirred media mill and ultrasonic homogenizer are introduced, their cell disruption mechanisms are discussed and their different applications compared. The impact of the results of micromechanical measurements on cell disruption devices will be discussed.