Handbook of Carbohydrate-Modifying Biocatalysts Pan Stanford Series on Biocatalysis Series Editor Peter Grunwald Titles in the Series Published Vol. 1 Industrial Biocatalysis Peter Grunwald, ed. 2015 978-981-4463-88-1 (Hardcover) 978-981-4463-89-8 (eBook) Vol. 2 Handbook of Carbohydrate-Modifying Biocatalysts Peter Grunwald, ed. 2016 978-981-4669-78-8 (Hardcover) 978-981-4669-79-5 (eBook) Forthcoming Vol. 3 Biocatalysis and Nanotechnology Peter Grunwald, ed. 2017 978-981-4613-69-9 (Hardcover) 978-981-4613-70-5 (eBook) Pan Stanford Series Handbook of on Biocatalysis Volume 2 Carbohydrate-Modifying Biocatalysts Peter Grunwald edited by PAN STANFORD PUBLISHING Published by Pan Stanford Publishing Pte. Ltd. Penthouse Level, Suntec Tower 3 8 Temasek Boulevard Singapore 038988 Email: [email protected] Web: www.panstanford.com British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Handbook of Carbohydrate-Modifying Biocatalysts Copyright © 2016 Pan Stanford Publishing Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. Cover image: Courtesy of Professor Jürgen Seibel, Institute of Organic Chemistry, Julius-Maximilians-University Würzburg, Germany. ISBN 978-981-4669-78-8 (Hardcover) ISBN 978-981-4669-79-5 (eBook) Printed in the USA Contents Preface  1 Basics in Carbohydrate Chemistry xxii1i Heinrich Hühnerfuss 1.1 Introduction 1 1.2 Classification of Carbohydrates 2 1.2.1 Monosaccharides 2 1.2.1.1 Configuration and nomenclature 4 1.2.1.2 Ring structures of carbohydrates 5 1.2.2 Disaccharides 10 1.2.3 Oligosaccharides 12 1.2.4 Polysaccharides 13 1.3 Reactions of carbohydrates 16 1.3.1 Oxidation of carbohydrates 16 1.3.2 Reduction of Carbohydrates 18 1.3.3 Nucleophilic Reactions 19 O N 1.3.4 Acylation and Alkylation of Monosaccharides 20 1.3.5 Formation of -Glycosides and -Glycosides 21  2 G1.l4y coGclyocnojupgraotteesin: As Brief Overview 2269 Peter Grunwald 2.1 Introduction 29 2.2 Glycoconjugates: General Features and Glycosylation 31 2.3 Glycoproteins 35 N 2.3.1 Recombinant Glycoproteins 37 2.4  -Glycosylation of Proteins 44 2.4.1 Quality Control and ER-Associated Degradation 47 2.4.2 Cytosolic Degradation 55 vi Contents 2.5   Mucins 61 2.6   Glycosaminoglycans and Proteoglycans 67  2.6.1 Heparin 69  2.6.2 Heparan Sulfate 71  2.6.3 Chondroitin and Dermatan Sulfate 73  2.6.4 Keratan Sulfate 75 2.7   Peptidoglycans 76 2.8   Glycolipids, Lipopolysaccharides, and Toxins 79  2.8.1 Lipopolysaccharides 83  2.8.2 Toxins 88 2.9   Carbohydrates and Antibiotics 91 2.10 Antibiotics and Resistance 98 2.11 Glycan Analysis Methods 104 2.12 Glyconanotechnology 111  3 2O.l1ig3o sCaocnchcalurdidiensg aRnedm Galrykcso conjugates in Recognition 115 Processes 147 Thisbe K. Lindhorst 3.1 Introduction 147 3.2 The Lectins and Their Ligands 148 3.2.1 Classification of Lectins 149 3.2.2 Characteristics of Important Lectin Classes 152 3.2.2.1 The R- and L-type lectins 152 3.2.2.2 The P-type lectins 153 3.2.2.3 The C-type lectins 154 3.2.2.4 The collectins: A subgroup of C-type lectins 156 3.2.2.5 The selectins: A subgroup of C-type lectins 156 3.2.2.6 The I-type lectins 159 3.2.2.7 The S-type lectins 161 3.3 Recognition of Carbohydrates 164 3.3.1 Formation of a Carbohydrate–Lectin Complex 164 3.3.2 Networks of Stabilizing Interactions 166 2+ 3.3.3 Complexation via Ca 170 Contents vii 3.3.4 Weak Interactions and the Role of Water 173 3.3.5 Hydrophobic Interactions with Carbohydrates 174 3.3.6 Binding to the Bacterial Lectin FimH 175 3.4 The Biological Role of Carbohydrate–Lectin Interactions 176 3.4.1 Clearance of Glycoproteins by Interaction with ASGPR 177 3.4.2 Leukocyte Trafficking 178 3.4.3 Galectins in Signaling 179 3.4.4 Type 1 Fimbriae-Mediated Bacterial Adhesion 184 3.5 Multivalency of Carbohydrate–Protein Interactions 185 3.6 Model Systems for the Investigation of Carbohydrate– Protein Interactions 192 3.6.1 Multivalent Glycomimetics: Glycodendrimers and Successors 193 3.6.2 Self-Assembled Monolayers: Glyco-SAMs 197 3.6.3 Testing Bacterial Adhesion 201 3.6.4 Tailoring Carbohydrate Surfaces to Mimic Cellular Adhesion to the Glycocalyx 204  4 3G.l7y coCsoindcel uHsyidornosl aasneds Outlook 220155 Motomitsu Kitaoka 4.1 Introduction 215 4.2 Classification 218 4.2.1 Anomeric Configuration of the Substrate 218 4.2.2 Location of the Hydrolyzed Linkage 218 4.2.3 Anomeric Retention and Inversion 219 4.3 Mechanisms of Action 220 4.3.1 Retaining GHs 220 4.3.1.1 Typical retaining GHs 220 4.3.1.2 Substrate-assisted catalysis of retaining GHs 221 + 4.3.1.3 NAD -dependent catalysis of retaining GHs 222 viii Contents 4.3.2 Inverting GHs 223 4.3.3 Hydrolysis and Transglycosylation 224 4.4 Chemoenzymatic Syntheses Using GHs with Engineered Substrates 227 4.5 Chemoenzymatic Syntheses Using Mutant GHs 228  5 4 D.i6sa cCcohnacrliudde iPnhgo Rsepmhoarryklsa ses: Mechanistic Diversity 232 and Application in the Glycosciences 237 Christiane Luley-Goedl and Bernd Nidetzky 5.1 Introduction 237 5.2 Disaccharide Phosphorylases: Classification, Structure, and Function 240 5.3 Phosphorylase Mechanisms 244 5.3.1 Cellobiose and Chitobiose Phosphorylase 244 aa 5.3.2 Sucrose Phosphorylase 248 5.3.3 Retaining , -Trehalose Phosphorylase 252 5.4 Novel Application of Disaccharide Phosphorylases in Synthesis 256 5.4.1 Multi-Step Enzymatic Synthesis of Disaccharides and Other Glycosides 260 N 5.4.1.1 Coupling to sucrose conversion 260 5.4.1.2 Lacto- -biose 261 5.4.1.3 Glucosylglycerol 263 5.4.2 Engineering of Cellobiose Phosphorylase for Altered Substrate Specificity 265  6 5D.i5h yCdoronxcylaucseiotonns e Phosphate-Dependent Aldolases: 266 From Flask Reaction to Cell-Based Synthesis 275 Mohui Wei, Zijie Li, Baolin Wu, Yunpeng Liu, Tiehai Li, Liuqing Wen, Jing Li, Jiansong Cheng, Junqiang Fang, Xianwei Liu, and Peng George Wang 6.1 Introduction 275 6.2 Synthetic Applications 276 6.3 DHAP Generation 278 Contents ix 6.4 Overcoming DHAP Dependence 280 6.4.1 Substrate/Reaction Engineering 280 6.4.2 Discovery and Design of New Enzymes 281 6.4.3 Directed Evolution of Enzymes 282 6.5 Transforming DHAP-Dependent Aldolase-Mediated Reactions from Flask into Cell-Based Synthesis 283  7 6En.6z yCmoantciclu asniodn C hemoenzymatic Synthesis of Nucleotide 291 Sugars: Novel Enzymes, Novel Substrates, Novel Products, and Novel Routes 297 Leonie Engels and Lothar Elling 7.1 Introduction 297 7.2 Novel Enzymes 301 7.2.1 UDP-Nucleotidylyltransferases 301 7.2.2 dTDP-Nucleotidylyltransferases 303 7.2.3 Salvage Pathway Enzymes 304 7.2.4 Glycosyltransferases 306 7.3 Novel Substrates and Novel Products 307 7.3.1 Screening of Novel Substrates 307 7.3.2 Novel Substrates for Nucleotidylyltransferases 309 7.3.3 Novel Substrates for Salvage Pathway Enzymes 310 7.3.4 Nucleotide Furanose Sugars 312 7.3.5 Nucleotide Phosphono Sugars 313 7.3.6 Nucleotide Carba Sugars 314 7.4 Novel Routes 314 7.4.1 Combinatorial Biocatalysis for in situ (Re)Generation of Nucleotide Sugars 314  8 7It.e5r aCtiovneclylu Asciotinnsg Glycosyltransferases 331251 Songya Zhang and Andreas Bechthold 8.1 Introduction 321 8.2 Iterative Acting GTs Involved in Polysaccharide Biosynthesis in Plants 323