Key Building Blocks via Enzyme-Mediated Synthesis, by Thomas Fischer and Jorg Pietruszka
*
Engineered Biosynthesis of Plant Polyketides: Structure-Based and Precursor-Directed Approach, by Ikuro Abe
*
Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others, by Joachim Stockigt, Zhong Chen, and Martin Ruppert
*
Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products, by Bohdan Ostash, Xiaohui Yan, Victor Fedorenko, and Andreas Bechthold
*
Total (Bio)Synthesis: Strategies of Nature and of Chemists, by Alexandra A. Roberts, Katherine S. Ryan, Bradley S. Moore, and Tobias A.M. Gulder"

The development of agents capable of cleaving RNA and DNA has attracted considerable attention from researchers in the last few years, because of the immediate and very important applications they can find in the emerging fields of biotechnology and pharmacology. There are essentially two classes of these agents - nucleases that occur naturally inside cells and synthetically produced artificial nucleases. The first class includes protein enzyme nucle ases and catalytic RNA structured ribozymes that perform cleavage of the phosphodiester bonds in nucleic acids according to a hydrolytic pathway in the course of different biochemical processes in the cell. A different pathway is used by some antibiotics which cleave DNA via redox-based mechanisms resulting in oxidative damage of nucleotide units and breakage of the DNA backbone. The above molecules are indispensable tools for manipulating nucleic acids and processing RNA; DNA-cleaving antibiotics and cytotoxic ribonucleases have demonstrated utility as chemotherapeutic agents. The second class, artificial nucleases, are rationally designed to imitate the active centers of natural enzymes by simple structures possessing minimal sets of the most important characteristics that are essential for catalysis. A dif ferent approach, in vitro selection, was also used to create artificial RNA and DNA enzymes capable of cleaving RNA. Being less efficient and specific as compared to the natural enzymes, the primitive mimics are smaller and robust and can function in a broad range of conditions."

Being small, shapeless and inert a gas molecule does not seem to be an enzyme's dream of a substrate. Nevertheless evolution has provided a host of enzymes which can interact specifically with gas molecules such as oxygen, carbon dioxide, nitrogen, hydrogen etc. Many of these enzymes play dominant roles on the world scene in biogeochemical cycles. On the cellular level they tend to be closely connected to the energy conserving apparatus. We define Gas Enzymology as the study of these enzymes. Historically, Gas Enzymology is a subspecialty of bioenergetics. Its foundations, technical as well as conceptual were laid by Warburg in his studies of the cellular combustion of nutrients. The Warburg apparatus supported the first thirty years of research in the field. It was succeeded by the Clark electrode which had its heyday during the period when the modern concepts of bioenergetics took shape. The Clark electrode, itself approaching thirty years of age, is now being sup plemented and in some cases replaced by the vastly more powerful membrane inlet mass spectrometer which measures with equal ease all dis solved gases of interest in biochemistry. It is our belief that future development of Gas Enzymology will be linked to the widespread exploit ation of this technique."

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized - and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.

Post-translational protein modifications by members of the ubiquitin family are widely recognized as important regulatory control systems for a variety of biological pathways. Their influence on eukaryotic cellular metabolism is comparable to that of other modifi- tions such as phosphorylation, acetylation and methylation. The small ubiquitin-related modifier SUMO uses a conjugation and de-conjugation system closely related to that of ubiquitin itself; yet, the functions of the SUMO system are highly diverse and largely independent of the ubiquitin system. SUMO modification controls the activity of tr- scription factors and can influence protein stability, but it also contributes to nucleo-cy- plasmic transport, chromosome segregation and DNA damage repair. As a consequence, the SUMO system pervades virtually all areas of basic molecular and cell biology, and scientists from different backgrounds, including medical researchers, are likely to enco- ter SUMO in the course of their studies. This volume, SUMO Protocols, therefore aims at presenting a collection of methods relevant to SUMO research in order to make these tools available to biochemists, molecular and cell biologists as well as research-oriented clinicians not yet familiar with the system. In contrast to the ubiquitin system, which has been the subject of several reviews and methods collections, no practical compendium entirely devoted to SUMO has been p- lished.

This book covers the most recent developments in the analysis of allosteric enzymes and provides a logical introduction to the limits for enzyme function as dictated by the factors that are limits for life. The book presents a complete description of all the mechanisms used for changing enzyme activity. It is extensively illustrated to clarify kinetic and regulatory properties. Eight enzymes are used as model systems after extensive study of their mechanisms. Wherever possible, the human form of the enzyme is used to illustrate the regulatory features.

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes."

The recognition of oxidative stress as a major factor in health, aging, and disease has led to a surge in research aimed at uncovering effective countermeasures in the form of antioxidants. Unique in its two-fold protective function, alpha-lipoic acid has drawn unprecedented interest as a coenzyme in mitochondrial energy metabolism and as an antioxidant and cell redox modulator. Mounting data regarding its potential health benefits demands an authoritative, single-source reference to codify current knowledge and guide future research. A state-of-the-science compilation, Lipoic Acid follows the history of this potent coenzyme and the latest discoveries regarding the chemistry, biological action, and significance in energy production, antioxidant activity, and health. The book is divided into three sections: * Section I: Discovery and Molecular Structure reviews the early studies leading to the discovery of alpha-lipoic acid and explains the molecular structure, biosynthesis, and the characterization of lipoic acid and its chemical derivatives. * Section II: Metabolic Aspects describes in detail the human pharmacokinetics of alpha-lipoic acid including the lipoic acid-derived dehydrogenase complexes and their roles in energy metabolism. It also explains antioxidant activity and redox modulation and how lipoic acid induces Phase II detoxification enzymes through activation of Nrf2-dependent gene expression. * Section III Clinical Aspects discusses enzyme deficiency disorders and the effects of lipoic acid on insulin. It defines lipoic acid influence on signaling pathways and AMP-activated kinase, and considers the therapeutic implications for treatment of metabolic syndromes and the improvement of mitochondrial function by lipoic acid supplementation. Contributions from leading in

Plant protease inhibitors are diverse in number and in specificity towards various proteolytic enzymes. This book focuses on the isolation, structure, characterization, physiochemical and physiological properties, synthesis, functions and mechanisms of action of plant protease inhibitors. It deals with their inhibitory effects on insects and pathogens and with their induction and introduction into plants by genetic engineering for plant protection. The induced resistance of insects to the inhibitors and the hazards to friendly insects are also discussed. Further, findings are presented on the cancer chemopreventive properties of the inhibitors at the cellular, tissue and organ levels and in the organism.

A quantitative description of the action of enzymes and other biological systems is both a challenge and a fundamental requirement for further progress in our und- standing of biochemical processes. This can help in practical design of new drugs and in the development of artificial enzymes as well as in fundamental understanding of the factors that control the activity of biological systems. Structural and biochemical st- ies have yielded major insights about the action of biological molecules and the mechanism of enzymatic reactions. However it is not entirely clear how to use this - portant information in a consistent and quantitative analysis of the factors that are - sponsible for rate acceleration in enzyme active sites. The problem is associated with the fact that reaction rates are determined by energetics (i. e. activation energies) and the available experimental methods by themselves cannot provide a correlation - tween structure and energy. Even mutations of specific active site residues, which are extremely useful, cannot tell us about the totality of the interaction between the active site and the substrate. In fact, short of inventing experiments that allow one to measure the forces in enzyme active sites it is hard to see how can one use a direct experimental approach to unambiguously correlate the structure and function of enzymes. In fact, in view of the complexity of biological systems it seems that only computers can handle the task of providing a quantitative structure-function correlation.

This is an introductory text intended to give the newcomer to this area a comprehensive insight into the science of biotransformations. The book traces the history of biotransformations, clearly spells out the pros and cons of conducting enzyme-mediated versus whole-cell bioconversions, and gives a variety of examples wherein the bio-reaction is a key element in a reaction sequence leading from cheap starting materials to valuable end-products (such as pharmaceuticals and agrochemicals, fragrances and flavors). The authors cover biotransformations involving the hydrolysis of esters, amides and nitriles, the synthesis of esters and amides, reduction and oxidation reactions and carbon-carbon bond-forming systems. The book finishes with a discussion of some industrially important large-scale bioconversions. The text will be suitable for advanced undergraduates, graduate students, and professionals in the areas of biochemistry, organic chemistry, biotechnology, microbiology, and industrial chemistry.

This is an introductory text intended to give the newcomer to this area a comprehensive insight into the science of biotransformations. The book traces the history of biotransformations, clearly spells out the pros and cons of conducting enzyme-mediated versus whole-cell bioconversions, and gives a variety of examples wherein the bio-reaction is a key element in a reaction sequence leading from cheap starting materials to valuable end-products (such as pharmaceuticals and agrochemicals, fragrances and flavors). The authors cover biotransformations involving the hydrolysis of esters, amides and nitriles, the synthesis of esters and amides, reduction and oxidation reactions and carbon-carbon bond-forming systems. The book finishes with a discussion of some industrially important large-scale bioconversions. The text will be suitable for advanced undergraduates, graduate students, and professionals in the areas of biochemistry, organic chemistry, biotechnology, microbiology, and industrial chemistry.

This textbook for advanced courses in enzyme chemistry and enzyme kinetics covers the field of steady-state enzyme kinetics from the basic principles inherent in the Henri equation to the expressions that describe the control of multi-enzyme pathways. Steady-state kinetic equations are derived with the use of the connection matrix method, and an algorithm is developed that can be implemented easily for computer-based derivation of the equations. Throughout the book emphasis is placed on a proper interpretation of the kinetic behavior of multi-reactant enzymic reactions and on the interpretation of control coefficients in terms of metabolic control. Problems are included at the end of each chapter and their solutions are found at the end of the book.

Enzymes in Action is a timely survey of a modern development in organic chemistry. It is clear that bioreagents demand that organic chemists think in a different way. If they do so, they will open up new avenues of exciting, new chemistry that will permit problems to be solved in an elegant way. The first section covers the concepts necessary to understand enzymes in molecular operations. The second section covers heteroatom enzyme chemistry, with considerable attention being given to the use of enzymes in the detoxification of chemical warfare agents and their application in environmental problems. The final section highlights the strategic use of enzymes in organic chemistry. It is clear that the term green chemistry' is appropriate, since enzyme mediated processes occur under mild, environmentally benign conditions, and enzymes enable chemists to perform new chemical operations that would otherwise be difficult to achieve at all.

This widely-praised textbook is particularly suited for advanced undergraduates or graduates in chemistry, biochemistry, medicinal chemistry, and pharmacology. The third edition has been substantially revised to reflect new research in the field, and features a major new chapter on self-assembly, auto-organization, and molecular devices. The outstanding figures remain a highlight of the book, and were described in an earlier edition as "the best I've seen for showing the organic chemistry of biomolecules." (Quart. Rev. Biol.)

Biological chemistry is a major frontier of inorganic chemistry. Three special volumes devoted to Metal Sites in Proteins and Models address the questions: how unusual ("entatic") are metal sites in metalloproteins and metalloenzymes compared to those in small coordination complexes? and if they are special, how do polypeptide chains and co-factors control this? The chapters deal with iron, with metal centres acting as Lewis acids, metals in phosphate enzymes, with vanadium, and with the wide variety of transition metal ions which act as redox centres. They illustrate in particular how the combined armoury of genetics and structure determination at the molecular level are providing unprecedented new tools for molecular engineering.

Since the pioneering work of U. S. VonEuler, G. O. Burr, B. Samuelsson, and others in the field of eicosanoids, research in this area continues to grow rapidly. Novel eicosanoids are being discovered even as enzymes that ca- lyze the synthesis of well-established eicosanoids are being critically studied with respect to their regulation and function. The novice in this field will most likely encounter three areas of intense research activity: regulation of expression and function of enzymes, i.e., ph- pholipases, cyclooxygenases, and lipoxygenases involved in the syntheses of established eicosanoids, characterization and distribution in tissues of eicosanoid receptors, and discovery and biologic roles of novel eicosanoids. This book is a compilation of chapters addressing these three areas. Most chapters of Eicosanoid Protocols address the first area, giving p- ticular emphasis to the cyclooxygenases and their two isoforms. This was done intentionally, because the discovery of the constitutive and inducible isoforms of this enzyme have introduced new concepts in the pathobiology of inflammation and in the use of nonsteroidal anti-inflammatory drugs. Although receptors of most established eicosanoids have been characterized and cloned, only one chapter (on the thromboxane A receptor) was devoted to this area.

The extracellular matrix is a network of fibres that hold cells together. It is broken down during normal physiological and disease processes such as bone remodelling, embryogenesis, cancer, and arthritis. This book is an up-to-date and comprehensive collection of data about the matrix metalloproteinases - enzymes which breakdown the extracellular matrix, and their specific inhibitors.

High Pressure Effects in Molecular Biophysics and Enzymology is designed to acquaint biochemists, biophysicists, and graduate students with advances in the application of high pressure in connection with spectroscopy as a research tool in the study of biomolecules. The 23 chapters written by leading authorities present an overview of current approaches to the use of high pressure in research on enzyme kinetics, protein folding and structure, lipid bilayer structure and organization, lipid-protein interaction, and DNA structure. This important, timely volume is the first devoted exclusively to high-pressure effects in biochemistry and will be the definitive reference in its subject for the next several years.

The first edition of this book covered the basic treatment of the enzyme reaction using the overall reaction kinetics and stopped-flow method, the general properties of protein and cofactors, the control of enzyme reaction, and the preparation of enzyme protein. These topics are the basis of enzyme research and thus suitable for the beginner in the field. The second edition presents the cofactors produced via the post-translational modification of the enzyme's active site. These cofactors expand the function of enzymes and open a new research field. The carbonyl reagent phenylhydrazine and related compounds have been useful in finding some of the newly discovered cofactors and thus have been discussed in this edition. The topic of the control of enzyme activity through the channel of substrates and products in polyfunctional enzymes has also been expanded in this book.

The scientist' s understanding of the cell at the molecular level has advanced rapidly over the last twenty years. This improved understa- ing has led to the development of many new laboratory methods that increasingly allow old problems to be tackled in new ways. Thus the modern scientist cannot specialize in just one field of knowledge, but must be aware of many disciplines. To aid the process of investigation, the Methods Molecular Biology series has brought together many protocols and has highlighted the useful variations and the pitfalls of the different methods. However, protocols frequently cannot be simply taken from the shelf. Thus the starting sample for a chosen protocol may be unavailable in the correct state or form, or the products of the procedure require a different sort of processing. Therefore the scientist needs more detailed information on the nature and requirements of the enzymes being used. This information, though usually available in the literature, is often widely dispersed and frequently occurs in older volumes of journals; not everyone has comprehensive library facilities available. Also many scientists searching out such information are not trained enzymologists and may be unaware of some of the parameters that are important in a specific enzyme reaction.

The scientist' s understanding of the cell at the molecular level has advanced rapidly over the last twenty years. This improved understa- ing has led to the development of many new laboratory methods that increasingly allow old problems to be tackled in new ways. Thus the modern scientist cannot specialize in just one field of knowledge, but must be aware of many disciplines. To aid the process of investigation, the Methods Molecular Biology series has brought together many protocols and has highlighted the useful variations and the pitfalls of the different methods. However, protocols frequently cannot be simply taken from the shelf. Thus the starting sample for a chosen protocol may be unavailable in the correct state or form, or the products of the procedure require a different sort of processing. Therefore the scientist needs more detailed information on the nature and requirements of the enzymes being used. This information, though usually available in the literature, is often widely dispersed and frequently occurs in older volumes of journals; not everyone has comprehensive library facilities available. Also many scientists searching out such information are not trained enzymologists and may be unaware of some of the parameters that are important in a specific enzyme reaction.

Isoenzymes were 'discovered' 20 years ago and were at first regarded as interesting but rare occurrences. Since then a wealth of information on enzyme heterogeneity has accrued and it now seems likely that at least half of all enzymes exist as isoenzymes. This is important in many areas of biological and medical science. Thus isoenzyme studies have provided the main experimental substance for the neutral drift controversy in genetics and evolution; they have greatly extended our understanding of metabolic regulation not only in animals but also in bacteria and plants; their existence has made available a multitude of highly sensitive markers for the study of differentiation and development, as well as providing indices of aberrant gene expression in carcinogenesis and other pathological processes. Iso enzymes are also being used increasingly in diagnostic clinical bio chemistry. It is surprising that this phenomenon which affects such a high pro portion of enzymes and is clearly important in biochemistry should receive such scant attention in the standard textbooks of that subject, the formal treatment of isoenzymology in these rarely exceeding one or two pages. This may be because the 'pure biochemist' has tended to regard variation in enzyme properties between tissues more as an unwanted complication than as a potential source of insight into diversity of biological function."

Comparative neurological studies of the evolutionary development of struc tures within the central nervous system of vertebrates have depended to a large extent upon morphological rather than functional criteria. Classical comparative anatomical studies, which have attempted to demonstrate homologies between parts of the brain in representatives of different vertebrate classes may be grouped under three general headings: 1. comparison of the embryological development of brain structures; 2. comparison in adult forms of the topographical relations of neuron groupings and fiber tracts, and of the morphology of cell types ( cyto architectonics); and 3. analysis and comparison of fiber connections between particular cell groupings or regions. Of these three, the third encompasses func tional relationships most directly, but even in well-defined fiber tracts the direction of conduction often remains indefinite, and the extent and activity of more diffuse systems is poorly known. In recent years a nurober of investigations applying electrophysiological and degeneration methods to submammalian forms have been reported. Those most pertinent to the present studies include the papers of . ARMSTRONG et al. (1953), KRUGERand associates (e. g. HERIC and KRUGER, 1966; KRUGERand BERKOWITZ, 1960; PowELL and KRUG ER, 1960}, GusEL'NIKov and SUPIN (1964) and KARA MYAN and BELEKJIOVA (1964) on various reptiles, and of PowELL and CowAN (1961), KARTEN and REVZIN (1966) and REVZIN and KARTEN (1967) on the pigeon.