DOCSLIB.ORG

^Wiley-Vch Iix

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
^Wiley-Vch Iix Enzyme Catalysis in Organic Synthesis A Comprehensive Handbook Volume III Edited by Karlheinz Drauz and Herbert Waldmann Second, Completely Revised and Enlarged Edition ^WILEY-VCH IIX Contents Foreword V Preface VII Volume I 1 Introduction 1 Maria-Regina Kula 1.1 Enzymes as Catalysts 1 1.2 Enzyme Structure and Function 4 (X^ 1.3 Cofactors and Coenzymes 12 1.4 Enzyme Nomenclature 21 1.5 Enzyme Kinetics 23 1.5.1 Reaction Rate and Substrate Concentration 23 1.5.2 Inhibitors and Effectors 26 1.5.3 Influence of pH and Buffers 27 1.5.4 Temperature 28 1.6 Organic Solvents as Reaction Media 31 1.7 Enzyme Handling: Quality Requirements 32 1.8 Biotransformation Using Whole Cells 33 1.8.1 General Aspects 33^ 1.8.2 Biotransformation with Growing Cells 36 1.8.3 Biotransformation with Resting Cells 37 1.8.4 Biotransformations with Permeabilized or Dried Cells 37 Bibliography 38 2 Production and Isolation of Enzymes 41 Yoshihiko Hirose 2.1 Introduction 41 2.2 Enzyme Suppliers for Biotransformation 44 2.3 Origins of Enzymes 45 2.3.1 Microbial Enzymes 45 2.3.2 Plant Enzymes 46 2.3.3 Animal enzymes 46 X| Contents 2.4 Fermentation of Enzymes 46 2.4.1 Liquid Fermentation 46 2.4.2 Solid Fermentation 47 2.4.3 Extraction of Enzymes 47 2.5 ExtractionofEnzym.es 47 2.5.1 Microbial Enzymes 47 2.5.2 Plant Enzymes 48 2.5.3 Animal Enzymes 48 2.6 Concentration 48 2.7 Purification of Enzymes 49 2.7.1 Chromatography 49 2.7.1.1 Ion Exchange Chromatography (IEX) 49 2.7.1.2 Hydrophobic Interaction Chromatography (HIC) 54 2.7.1.3 Gel Filtration (GF) 56 2.7.1.4 Reversed Phase Chromatography 58 , 2.7.1.5 Hydrogen Bond Chromatography 59 2.7.1.6 Affinity Chromatography 59 2.7.1.7 Salting-out Chromatography 62 2.7.2 Precipitation 62 2.7.2.1 Precipitation by Salting out 62 2.7.2.2 Precipitation by Organic Solvents 63 2.7.2.3 Precipitation by Changing pH 63 2.7.2.4 Precipitation by Water-Soluble Polymer 63 2.7.3 Crystallization 64 2.7.4 Stabilization During Purification 64 2.7.5 Storage of Enzymes 64 2.7.5.1 Storage in Liquids 64 2.7.5.2 Storage in Solids 65 2.8 Commercial Biocatalysts 65 References 66 3 Rational Design of Functional Proteins 67 Tadayuki Imanaka and Haruyuki Atomi 3.1 Protein Engineering 67 3.2 Gene Manipulation Techniques in Enzyme Modification 68 3.3 Protein Crystallization 70 3.4 Comparative Modeling of a Protein Structure 73 3.5 What is Needed to Take a Rational Approach? 75 3.6 Examples of Protein Engineering 76 3.6.1 Protein Engineering Studies: Providing a Rational Explanation for Enzyme Specificity 76 3.6.2 Enhancing the Thermostability of Proteases 78 3.6.3 Contribution of Ion Pairs to the Thermostability of Proteins from Hyperthermophiles 79 Contents XI 3.6.4 Thermostability Engineering Based on the Consensus Concept 80 3.6.5 Changing the Optimal pH of an Enzyme 81 3.6.6 Changing the Cofactor Specificity of an Enzyme 82 3.6.7 Changing the Substrate Specificity of an Enzyme 84 3.6.8 Changing the Product Specificity of an Enzyme 85 3.6.9 Combining Site-directed Mutagenesis with Chemical Modification 86 3.6.10 Changing the Catalytic Activity of a Protein 087 3.7 Conclusions 89 References 90 4 Enzyme Engineering by Directed Evolution 95 Oliver May, Christopher A. Voigt and Frances H. Arnold 4.1 Introduction 95 4.2 Evolution as an Optimizing Process 96 4.2.1 The Search Space of Chemical Solutions 97 4.2.2 The Directed Evolution Algorithm 98 4.3 Creating a Library of Diverse Solutions 99 4.3.1 Mutagenesis 99 4.3.1.1 Random Point Mutagenesis of Whole Genes 99 4.3.1.2 Focused Mutagenesis 104 4.3.1.3 Calculation of Mutagenesis Hot-Spots 105 4.3.2 Recombination 107 4.3.2.1 In Vitro Recombination 107 4.3.2.2 In vivo Recombination 110 4.3.2.3 Family Shuffling 111 4.4 Finding Improved Enzymes: Screening and Selection 112 4.4.1 You Get What You Screen For 113 4.4.2 Screening Strategies 113 4.4.2.1 Low-Throughput Screening 114 4.4.2.2 High-Throughput Screening 115 4.4.2.3 Choosing Low versus High Throughput 116 4.4.2.4 Analyzing the Mutant Fitness Distribution 117 4.4.3 Selection and Methods to link Genotype with Phenotype 119 4.5 Applications of Directed Evolution 121 4.5.1 Improving Functional Enzyme Expression and Secretion 122 4.5.2 Engineering Enzymes for Non-natural Environments 127 4.5.3 Engineering Enzyme Specificity 129 4.5.3.1 Substrate Specificity 129 4.5.3.2 Enantioselectivity 131 4.6 Conclusions 132 References 133 XIII Contents 5 Enzyme Bioinformatics 139 Kay Hofmann • - 5.1 Introduction 139 5.2 Protein Comparison 140 5.2.1 Sequence Comparison versus Structure Comparison 140 5.2.2 Substitution Matrices in Sequence Comparisons 141 5.2.3 Profile Methods 142 5.2.4 Database Searches 144 5.3 Enzyme-specific Conservation Patterns 145 5.3.1 General Conservation Patterns 145 5.3.2 Active Site Conservation Patterns 146 5.3.3 Metal Binding Conservation Patterns 146 5.3.4 Making Use of Conservation Patterns 148 5.4 Modular Enzymes 149 5.4.1 The Domain Concept in Structure and Sequence 149 5.4.2 A Classification of Modular Enzymes 150 5.4.3 Inhibitory Domains 151 5.5 Enzyme Databases and Other Information Sources 151 5.5.1 E. C. Nomenclature and ENZYME Database 152 5.5.2 BRENDA 152 5.5.3 KEGG and LIGAND database 153 5.5.4 UM-BBD 153 5.5.5 Structural Databases 153 5.5.6 Metalloprotein Databases 154 5.5.7 Databases for Selected Enzyme Classes 154 5.6 Protein Domain and Motif Databases 154 5.6.1 PROSITEea55 5.6.2 PFAM 156 5.6.3 Other Related Databases 156 5.7 Enzyme Genomics 156 5.7.1 Ortholog Search 157 5.7.2 Paralog Search 157 5.7.3 Non-homology Based methods 159 5.8 Outlook 159 References 161 6 Immobilization of Enzymes 163 James Lalonde 6.1 Introduction 163 6.2 Methods of Immobilization 164 6.2.1 Non-Covalent Adsorption 165 6.2.2 Covalent Attachment 168 6.2.2.1 Carriers for Enzyme Immobilization 170 6.2.3 Entrapment and Encapsulation 171 Contents XIII 6.2.4 Cross-Linking 175 6.3 Properties of Immobilized Biocatalysts 175 6.3.1 Mass Transfer Effects 176 6.3.2 Partition 176 6.3.3 Stability 177 6.3.4 Activity of Immobilized Enzymes 177 6.4 New Developments and Outlook 178 6.4.1 Cross-linked Enzyme Crystals (CLEC®) 179 6.4.2 Sol-Gel 181 6.4.3 Controlled Solubility "Smart Polymers" 181 References 182 7 Reaction Engineering for Enzyme-Catalyzed Biotransformations 185 Manfred Biselli, Udo Kragl and Christian Wandrey 7.1 Introduction 185 7.2 Steps of Process Optimization 186 7.3 Investigation of the Reaction System 190 7.3.1 Properties of the Enzyme 190 7.3.2 Properties of the Reaction System 193 7.3.2.1 Thermodynamic Equilibrium of the Reaction 193 7.3.2.2 Complex Reaction Systems: The Existence of Parallel and Consecutive Reactions 195 7.3.2.3 Other Properties of the Reaction System 204 7.3.2.4 Application of Organic Solvents 204 7.4 Investigation of Enzyme Kinetics 208 7.4.1 Methods of Parameter Identification 209 7.4.2 The Kinetics of One-Enzyme Systems 210 7.4.2.1 THE Michaelis-Menten Kinetics 210 7.4.2.2 Competitive Inhibition 214 7.4.2.3 Non-Competitive Inhibition 215 7.4.2.4 Uncompetitive Inhibition 216 7.4.2.5 Reversibility of One-Substrate Reactions 217 7.4.2.6 Two-Substrate Reactions 218 7.4.2.7 Kinetics of Aminoacylase as Example of a Random Uni-Bi Mechanism 223 7.4.3 Kinetics of Multiple Enzyme Systems 230 7.5 Enzyme Reactors 232 7.5.1 Basic Reaction Engineering Aspects 232 7.5.2 Reactors for Soluble Enzymes 238 7.5.2.1 Reactor Optimization Exemplified by the Enzyme Membrane Reactor 241 7.5.2.2 Control of Conversion in a Continuously Operated EMR 249 7.5.3 Reactor Systems for Immobilized Enzymes 250 7.5.4 Reaction Techniques for Enzymes in Organic Solvent 251 XIV I Contents 7.6 Conclusions and Outlook 253 References 254 8 Enzymic Conversions in Organic and Other Low-Water Media 259 Peter Hailing 8.1 Introduction 259 8.2 Enzyme Form 260 8.2.1 Lyophilized Powders 260 8.2.2 Immobilized Enzymes 261 8.2.3 Cross-Linked Crystals 261 8.2.4 Direct Precipitation in Organic Solvents 262 8.2.5 Additives in Catalyst Powders 262 8.2.6 Solubilized Enzymes 263 8.3 Residual Water Level 264 8.3.1 Fixing Initial Water Activity of Reaction Components 266 • 8.3.2 Control of Water Activity During Reaction 269 8.3.3 "Water Mimics" 273 8.4 Temperature 274 8.5 Substrate (Starting Material) Concentrations 274 8.6 Solvent Choice 276 8.6.1 Effects on Equilibrium Position 276 8.6.2 "Solvent Effects" that Really are Not 276 8.6.3 Solvent Polarity Trend and Recommended Choices 277 8.6.4 Solvent Parameters 279 8.6.5 Solvent Effects on Selectivity 280 8.6.6 No Solvent or Little Solvent Systems 280 8.7 Acid-Base Conditions 281 8.7.1 pH Memory 281 8.7.2 Processes Erasing pH Memory 282 8.7.3 Systems for Acid-Base Buffering 283 References 285 9 Enzymatic Kinetic Resolution 287 Jonathan M.J.
Load more

Recommended publications
  • Transcriptomic Characterization of Bradyrhizobium Diazoefficiens
    International Journal of Molecular Sciences Article Transcriptomic Characterization of Bradyrhizobium diazoefficiens Bacteroids Reveals a Post-Symbiotic, Hemibiotrophic-Like Lifestyle of the Bacteria within Senescing Soybean Nodules Sooyoung Franck 1, Kent N. Strodtman 1 , Jing Qiu 2 and David W. Emerich 1,* 1 Division of Biochemistry, University of Missouri, Columbia, MO 65211, USA; [email protected] (S.F.); [email protected] (K.N.S.) 2 Applied Economics and Statistics, University of Delaware, Newark, DE 19716, USA; [email protected] * Correspondence: [email protected]; Tel: +1-573-882-4252 Received: 8 October 2018; Accepted: 28 November 2018; Published: 7 December 2018 Abstract: The transcriptional activity of Bradyrhizobium diazoefficens isolated from soybean nodules was monitored over the period from symbiosis to late plant nodule senescence. The bacteria retained a near constant level of RNA throughout this period, and the variation in genes demonstrating increased, decreased, and/or patterned transcriptional activity indicates that the bacteria are responding to the changing environment within the nodule as the plant cells progress from an organized cellular structure to an unorganized state of internal decay. The transcriptional variation and persistence of the bacteria suggest that the bacteria are adapting to their environment and acting similar to hemibiotrophs, which survive both as saprophytes on live plant tissues and then as necrophytes on decaying plant tissues. The host plant restrictions of symbiosis make B. diazoefficiens a highly specialized, restricted hemibiotroph. Keywords: bradyrhizobium diazoefficiens; soybean; Glycine max; nitrogen fixation; senescence; transcriptomics; hemibiotroph 1. Introduction Soybean nodules are symbiotic organs that are formed on roots by the complex interaction between soybean plants and rhizobia, nitrogen-fixing bacteria, under nitrogen-limiting conditions.
    [Show full text]
  • CDH12 Cadherin 12, Type 2 N-Cadherin 2 RPL5 Ribosomal
    5 6 6 5 . 4 2 1 1 1 2 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 A A A A A A A A A A A A A A A A A A A A C C C C C C C C C C C C C C C C C C C C R R R R R R R R R R R R R R R R R R R R B , B B B B B B B B B B B B B B B B B B B , 9 , , , , 4 , , 3 0 , , , , , , , , 6 2 , , 5 , 0 8 6 4 , 7 5 7 0 2 8 9 1 3 3 3 1 1 7 5 0 4 1 4 0 7 1 0 2 0 6 7 8 0 2 5 7 8 0 3 8 5 4 9 0 1 0 8 8 3 5 6 7 4 7 9 5 2 1 1 8 2 2 1 7 9 6 2 1 7 1 1 0 4 5 3 5 8 9 1 0 0 4 2 5 0 8 1 4 1 6 9 0 0 6 3 6 9 1 0 9 0 3 8 1 3 5 6 3 6 0 4 2 6 1 0 1 2 1 9 9 7 9 5 7 1 5 8 9 8 8 2 1 9 9 1 1 1 9 6 9 8 9 7 8 4 5 8 8 6 4 8 1 1 2 8 6 2 7 9 8 3 5 4 3 2 1 7 9 5 3 1 3 2 1 2 9 5 1 1 1 1 1 1 5 9 5 3 2 6 3 4 1 3 1 1 4 1 4 1 7 1 3 4 3 2 7 6 4 2 7 2 1 2 1 5 1 6 3 5 6 1 3 6 4 7 1 6 5 1 1 4 1 6 1 7 6 4 7 e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m
    [Show full text]
  • Supplementary Materials
    Supplementary Materials COMPARATIVE ANALYSIS OF THE TRANSCRIPTOME, PROTEOME AND miRNA PROFILE OF KUPFFER CELLS AND MONOCYTES Andrey Elchaninov1,3*, Anastasiya Lokhonina1,3, Maria Nikitina2, Polina Vishnyakova1,3, Andrey Makarov1, Irina Arutyunyan1, Anastasiya Poltavets1, Evgeniya Kananykhina2, Sergey Kovalchuk4, Evgeny Karpulevich5,6, Galina Bolshakova2, Gennady Sukhikh1, Timur Fatkhudinov2,3 1 Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia 2 Laboratory of Growth and Development, Scientific Research Institute of Human Morphology, Moscow, Russia 3 Histology Department, Medical Institute, Peoples' Friendship University of Russia, Moscow, Russia 4 Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia 5 Information Systems Department, Ivannikov Institute for System Programming of the Russian Academy of Sciences, Moscow, Russia 6 Genome Engineering Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia Figure S1. Flow cytometry analysis of unsorted blood sample. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S2. Flow cytometry analysis of unsorted liver stromal cells. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S3. MiRNAs expression analysis in monocytes and Kupffer cells. Full-length of heatmaps are presented.
    [Show full text]
  • Colletotrichum Graminicola</Em>
    University of Kentucky UKnowledge Plant Pathology Faculty Publications Plant Pathology 3-8-2016 A Colletotrichum graminicola Mutant Deficient in the Establishment of Biotrophy Reveals Early Transcriptional Events in the Maize Anthracnose Disease Interaction Maria F. Torres University of Kentucky, [email protected] Noushin Ghaffari Texas A&M University Ester A. S. Buiate University of Kentucky, [email protected] Neil Moore University of Kentucky, [email protected] Scott chS wartz Texas A&M University FSeoe nelloxtw pa thige fors aaddndition addal aitutionhorsal works at: https://uknowledge.uky.edu/plantpath_facpub Part of the Bioinformatics Commons, Genomics Commons, Integrative Biology Commons, and Right click to open a feedback form in a new tab to let us know how this document benefits oy u. the Plant Pathology Commons Repository Citation Torres, Maria F.; Ghaffari, Noushin; Buiate, Ester A. S.; Moore, Neil; Schwartz, Scott; Johnson, Charles D.; and Vaillancourt, Lisa J., "A Colletotrichum graminicola Mutant Deficient in the Establishment of Biotrophy Reveals Early Transcriptional Events in the Maize Anthracnose Disease Interaction" (2016). Plant Pathology Faculty Publications. 53. https://uknowledge.uky.edu/plantpath_facpub/53 This Article is brought to you for free and open access by the Plant Pathology at UKnowledge. It has been accepted for inclusion in Plant Pathology Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Maria F. Torres, Noushin Ghaffari, Ester A. S. Buiate, Neil Moore, Scott chS wartz, Charles D. Johnson, and Lisa J. Vaillancourt A Colletotrichum graminicola Mutant Deficient in the Establishment of Biotrophy Reveals Early Transcriptional Events in the Maize Anthracnose Disease Interaction Notes/Citation Information Published in BMC Genomics, v.17, 202, p.
    [Show full text]
  • Transcriptomic and Proteomic Profiling Provides Insight Into
    BASIC RESEARCH www.jasn.org Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy † † ‡ Peidi Liu,* Emelie Lassén,* Viji Nair, Celine C. Berthier, Miyuki Suguro, Carina Sihlbom,§ † | † Matthias Kretzler, Christer Betsholtz, ¶ Börje Haraldsson,* Wenjun Ju, Kerstin Ebefors,* and Jenny Nyström* *Department of Physiology, Institute of Neuroscience and Physiology, §Proteomics Core Facility at University of Gothenburg, University of Gothenburg, Gothenburg, Sweden; †Division of Nephrology, Department of Internal Medicine and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; ‡Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; |Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; and ¶Integrated Cardio Metabolic Centre, Karolinska Institutet Novum, Huddinge, Sweden ABSTRACT IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes.
    [Show full text]
  • University of London Thesis
    REFERENCE ONLY UNIVERSITY OF LONDON THESIS Degree Year^^0^ Name of Author C O P Y R IG H T This is a thesis accepted for a Higher Degree of the University of London. It is an unpublished typescript and the copyright is held by the author. All persons consulting the thesis must read and abide by the Copyright Declaration below. COPYRIGHT DECLARATION I recognise that the copyright of the above-described thesis rests with the author and that no quotation from it or information derived from it may be published without the prior written consent of the author. LOANS Theses may not be lent to individuals, but the Senate House Library may lend a copy to approved libraries within the United Kingdom, for consultation solely on the premises of those libraries. Application should be made to: Inter-Library Loans, Senate House Library, Senate House, Malet Street, London WC1E 7HU. REPRODUCTION University of London theses may not be reproduced without explicit written permission from the Senate House Library. Enquiries should be addressed to the Theses Section of the Library. Regulations concerning reproduction vary according to the date of acceptance of the thesis and are listed below as guidelines. A. Before 1962. Permission granted only upon the prior written consent of the author. (The Senate House Library will provide addresses where possible). B. 1962- 1974. In many cases the author has agreed to permit copying upon completion of a Copyright Declaration. C. 1975 - 1988. Most theses may be copied upon completion of a Copyright Declaration. D. 1989 onwards. Most theses may be copied.
    [Show full text]
  • 257 Absolute Configuration 39, 75 – of L-(+)-Alanine 83
    257 Index a L-aminoacylase 246 absolute configuration 39, 75 amount of substance 12 –ofL-(+)-alanine 83 asymmetric atom 39 – by anomalous dispersion effect in X-ray asymmetric disequilibrating transformation crystallography 78 151 – by chemical correlation 79 asymmetric induction 143 – correlation strategies 80 – of second kind 151 – by direct methods 78 asymmetric synthesis 139 – extended sense of 77 asymmetric transformation –ofD-glyceraldehyde 39 – of second kind 151 –ofD-(+)-glyceraldehyde 77 asymmetric transformation of the second kind – by indirect methods 79 173 –ofD-(–)-lactic acid 81 atropisomer 44, 73 – methods of determination 78 atropisomerism 24, 71 – of natural glucose 78, 82 autocatalysis – by predictive calculation of chiroptical data – a special case of organocatalysis 234 79 autocatalytic effect –of(R,R)-(+)-tartaric acid 78, 82 – of a zinc complex 238 achiral bidentate reagent Avogadro constant 12 – purification of enantiomers with 149 axial chirality 39, 44 achiral stationary phase 95 achirality, achiral 24, 29 b aci form 113 Baeyer–Villiger oxidation acylase I 161 – enanatiotope selective 253 AD-mix- 229 – enzymatic 253 AD-mix- 229 – microbial 166 alcohol dehydrogenases – regio- and enanatiomer selective 253 – Prelog’s rule 252 baker’s yeast aldol reactions – regio-, enantiotope and diastereotope – catalyzed with chiral ionic liquid 238 selective reduction with 186 – catalytic, double enantiotope selective 238 bidentate achiral reagent 90 – completely syn diastereoselective 238 Bijvoet, J. M. 78 – stereoselctive 209 BINAL-H 212 allene 44 BINAP amide-imido acid tautomerism 112 – ruthenium complex of 214 amino acids biocatalysis 244 enantiopure, D-andL- 250 – advantages of 245 D-amino acid oxidase 100 – disadvantages of 245 Stereochemistry and Stereoselective Synthesis: An Introduction, First Edition.
    [Show full text]
  • SI Appendix Index 1
    SI Appendix Index Calculating chemical attributes using EC-BLAST ................................................................................ 2 Chemical attributes in isomerase reactions ............................................................................................ 3 Bond changes …..................................................................................................................................... 3 Reaction centres …................................................................................................................................. 5 Substrates and products …..................................................................................................................... 6 Comparative analysis …........................................................................................................................ 7 Racemases and epimerases (EC 5.1) ….................................................................................................. 7 Intramolecular oxidoreductases (EC 5.3) …........................................................................................... 8 Intramolecular transferases (EC 5.4) ….................................................................................................. 9 Supporting references …....................................................................................................................... 10 Fig. S1. Overview …............................................................................................................................
    [Show full text]
  • This Thesis Has Been Submitted in Fulfilment of the Requirements for a Postgraduate Degree (E.G
    This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Biocatalytic application of rare PLP- dependent aminotransferases for the synthesis of high value amino acids and amines Annabel Serpico A Thesis Submitted for the Degree of Doctor of Philosophy The University of Edinburgh 2018 Lay Summary Traditional chemical approaches for the production of compounds often rely on harsh conditions such as high temperature and pressure and create toxic waste and pollutants. Moreover, these reactions are often non efficient, creating unwanted side products that need to be disposed of. A very important branch of chemistry, called green chemistry, supports the design of products and processes that use the least amount of dangerous substances as they can. An important aspect of green chemistry is biocatalysis, which consists of the use of biological systems, either whole cells or enzymes for the production of compounds.
    [Show full text]
  • Oxidized Phospholipids Regulate Amino Acid Metabolism Through MTHFD2 to Facilitate Nucleotide Release in Endothelial Cells
    ARTICLE DOI: 10.1038/s41467-018-04602-0 OPEN Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells Juliane Hitzel1,2, Eunjee Lee3,4, Yi Zhang 3,5,Sofia Iris Bibli2,6, Xiaogang Li7, Sven Zukunft 2,6, Beatrice Pflüger1,2, Jiong Hu2,6, Christoph Schürmann1,2, Andrea Estefania Vasconez1,2, James A. Oo1,2, Adelheid Kratzer8,9, Sandeep Kumar 10, Flávia Rezende1,2, Ivana Josipovic1,2, Dominique Thomas11, Hector Giral8,9, Yannick Schreiber12, Gerd Geisslinger11,12, Christian Fork1,2, Xia Yang13, Fragiska Sigala14, Casey E. Romanoski15, Jens Kroll7, Hanjoong Jo 10, Ulf Landmesser8,9,16, Aldons J. Lusis17, 1234567890():,; Dmitry Namgaladze18, Ingrid Fleming2,6, Matthias S. Leisegang1,2, Jun Zhu 3,4 & Ralf P. Brandes1,2 Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a cau- sal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipo- proteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2- controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
    [Show full text]
  • 12) United States Patent (10
    US007635572B2 (12) UnitedO States Patent (10) Patent No.: US 7,635,572 B2 Zhou et al. (45) Date of Patent: Dec. 22, 2009 (54) METHODS FOR CONDUCTING ASSAYS FOR 5,506,121 A 4/1996 Skerra et al. ENZYME ACTIVITY ON PROTEIN 5,510,270 A 4/1996 Fodor et al. MICROARRAYS 5,512,492 A 4/1996 Herron et al. 5,516,635 A 5/1996 Ekins et al. (75) Inventors: Fang X. Zhou, New Haven, CT (US); 5,532,128 A 7/1996 Eggers Barry Schweitzer, Cheshire, CT (US) 5,538,897 A 7/1996 Yates, III et al. s s 5,541,070 A 7/1996 Kauvar (73) Assignee: Life Technologies Corporation, .. S.E. al Carlsbad, CA (US) 5,585,069 A 12/1996 Zanzucchi et al. 5,585,639 A 12/1996 Dorsel et al. (*) Notice: Subject to any disclaimer, the term of this 5,593,838 A 1/1997 Zanzucchi et al. patent is extended or adjusted under 35 5,605,662 A 2f1997 Heller et al. U.S.C. 154(b) by 0 days. 5,620,850 A 4/1997 Bamdad et al. 5,624,711 A 4/1997 Sundberg et al. (21) Appl. No.: 10/865,431 5,627,369 A 5/1997 Vestal et al. 5,629,213 A 5/1997 Kornguth et al. (22) Filed: Jun. 9, 2004 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2005/O118665 A1 Jun. 2, 2005 EP 596421 10, 1993 EP 0619321 12/1994 (51) Int. Cl. EP O664452 7, 1995 CI2O 1/50 (2006.01) EP O818467 1, 1998 (52) U.S.
    [Show full text]
  • Of Pseudomonas Sp. Strain NS671 Expressed In
    JOURNAL OF BACTERIOLOGY, Dec. 1992, p. 7989-7995 Vol. 174, No. 24 0021-9193/92/247989-07$02.00/0 Copyright X) 1992, American Society for Microbiology Purification and Characterization of the Hydantoin Racemase of Pseudomonas sp. Strain NS671 Expressed in Escherichia coli KEN WATABE,* TAKAHIRO ISHIKAWA, YUKUO MUKOHARA, AND HIROAKI NAKAMURA Odawara Research Center, Nippon Soda Co., Ltd., 345 Takada, Odawara, Kanagawa 250-02, Japan Received 16 July 1992/Accepted 19 October 1992 The hydantoin racemase gene ofPseudomonas sp. strain NS671 had been cloned and expressed in Escherichia coli. Hydantoin racemase was purified from the cell extract of the E. coli strain by phenyl-Sepharose, DEAE-Sephacel, and Sephadex G-200 chromatographies. The purified enzyme had an apparent molecular mass of 32 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. By gel filtration, a molecular mass of about 190 kDa was found, suggesting that the native enzyme is a hexamer. The optimal conditions for hydantoin racemase activity were pH 9.5 and a temperature of 45°C. The enzyme activity was slightly stimulated by the addition of not only Mn2+ or Co2' but also metal-chelating agents, indicating that the enzyme is not a metalloenzyme. On the other hand, Cu2' and Zn2+ strongly inhibited the enzyme activity. Kinetic studies showed substrate inhibition, and the V.. values for D- and L-5-(2-methylthioethyl)hydantoin were 35.2 and 79.0 ,umol/min/mg of protein, respectively. The purified enzyme did not racemize 5-isopropyl- hydantoin, whereas the cells ofE. coli expressing the enzyme are capable of racemizing it.
    [Show full text]