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Applied Biocatalysis: From Fundamental Science to Industrial Applications

Lutz Hilterhaus (Editor), Andreas Liese (Editor), Ulrich Kettling (Editor), Garabed Antranikian (Editor)
ISBN: 978-3-527-33669-2
464 pages
September 2016
Applied Biocatalysis: From Fundamental Science to Industrial Applications (3527336699) cover image

Description

This reference book originates from the interdisciplinary research cooperation between academia and industry. In three distinct parts, latest results from basic research on stable enzymes are explained and brought into context with possible industrial applications. Downstream processing technology as well as biocatalytic and biotechnological production processes from global players display the enormous potential of biocatalysts. Application of "extreme" reaction conditions (i.e. unconventional, such as high temperature, pressure, and pH value) - biocatalysts are normally used within a well defined process window - leads to novel synthetic effects. Both novel enzyme systems and the synthetic routes in which they can be applied are made accessible to the reader. In addition, the complementary innovative process technology under unconventional conditions is highlighted by latest examples from biotech industry.
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Table of Contents

List of Contributors XVII

Preface XXV

Part A Molecular Biology, Enzyme Screening and Bioinformatics 1

1 Engineering Lipases with an Expanded Genetic Code 3
Alessandro De Simone,Michael Georg Hoesl, and Nediljko Budisa

1.1 Introduction 3

1.2 Enzyme Activity of Lipases from Different Sources and Engineering Approaches 4

1.3 Noncanonical Amino Acids in Lipase Design and Engineering 5

1.4 Case Study: Manipulating Proline, Phenylalanine, and Methionine Residues in Lipase 7

1.5 “Unnatural” Lipases Are Able to Catalyze Reactions under Different Hostile Environments 8

1.6 Lipase Engineering via Bioorthogonal Chemistries: Activity and Immobilization 9

1.7 Conclusions and Perspectives 10

References 11

2 Screening of Enzymes: Novel Screening Technologies to Exploit Noncultivated Microbes for Biotechnology 13
Jennifer Chow and Wolfgang R. Streit

2.1 Introduction 13

2.2 Sequence- versus Function-Based Metagenomic Approach to Find Novel Biocatalysts 14

2.3 Alternative Hosts, Metatranscriptomics, and Metaproteomics 25

2.4 Future Perspectives 26

References 27

3 Robust Biocatalysts – Routes to New Diversity 31
Anna Krüger, Skander Elleuche, Kerstin Sahm, and Garabed Antranikian

3.1 Introduction 31

3.2 Metagenomics to Retrieve New Genes from Extremophilic Microorganisms 32

3.3 Microbial Expression Hosts for the Production of Extremozymes 36

3.4 Molecular Biology Approaches for Enzyme Improvement 39

3.5 Conclusions and Future Perspectives 45

References 46

4 Application of High-Throughput Screening in Biocatalysis 53
Xin Ju, Jie Zhang, Kui Chan, Xiaoliang Liang, Junhua Tao, and Jian-He Xu

4.1 Introduction 53

4.2 Discussions 54

4.3 Summary 68

References 68

5 Supporting Biocatalysis Research with Structural Bioinformatics 71
Nadine Schneider, Andrea Volkamer, Eva Nittinger, and Matthias Rarey

5.1 Introduction 71

5.2 Computational Tools to Assist Biocatalysis Research 71

5.3 From Active Site Analysis to Protein Stability Considerations 75

5.4 Applying DoGSiteScorer and HYDE to Biocatalytical Questions 85

5.5 Conclusion and Future Directions 95

Acknowledgments 96

References 97

6 Engineering Proteases for Industrial Applications 101
Ljubica Vojcic, Felix Jakob, Ronny Martinez, Hendrik Hellmuth, Timothy O’Connell, Helge Mühl, Michael G. Lorenz, and Ulrich Schwaneberg

6.1 Proteases in Industry 101

6.2 Serine Proteases and Subtilisins 102

6.3 Proteases as Additives in Laundry Detergents 104

6.4 Engineering B. lentus Alkaline Protease toward Increased Inhibition by Benzylmalonic Acid 105

6.5 Engineering Subtilisin Protease toward Increased Oxidative Resistance 108

6.6 Increasing Protease Tolerance against Chaotropic Agents 111

6.7 Directed Evolution of Subtilisin E toward High Activity in the Presence of Guanidinium Chloride and Sodium Dodecylsulfate 112

6.8 Summary 116

Acknowledgment 116

References 117

Part B Biocatalytic Synthesis 121

7 Biocatalytic Synthesis of Natural Products by O-Methyltransferases 123
Ludger Wessjohann, Anne-Katrin Bauer, Martin Dippe, Jakob Ley, and Torsten Geißler

7.1 Introduction 123

7.2 Classification and Mechanistic Aspects of O-Methyltransferases 124

7.3 Cofactor Dependence and Regeneration 126

7.4 Natural OMT Products in Industrial Applications 129

7.5 OMTs in Biocatalytic Synthesis 132

7.6 Challenges and Perspectives 139

7.7 Conclusions 141

Abbreviations 141

Acknowledgments 142

References 142

8 Biocatalytic Phosphorylation of Metabolites 147
Dominik Gauss, Bernhard Schönenberger, Getachew S. Molla, Birhanu M. Kinfu, Jennifer Chow, Andreas Liese, Wolfgang R. Streit, and Roland Wohlgemuth

8.1 Introduction 147

8.2 Synthetic Aspects of Biocatalytic Phosphorylations 149

8.3 Development of Analytical Methods 152

8.4 Stability of Phosphorylated Metabolites 154

8.5 Phosphate Donors 156

8.6 Emerging Biocatalytic Phosphorylation Reactions 157

8.7 Reaction Engineering for Biocatalytic Phosphorylation Processes 160

8.8 Summary and Outlook 167

References 168

9 Flavonoid Biotechnology – New Ways to High-Added-Value Compounds 179
Ioannis V. Pavlidis, Mechthild Gall, Torsten Geißler, Egon Gross, and Uwe T. Bornscheuer

9.1 Flavonoids 179

9.2 Metabolic Pathways of Flavonoids 182

9.3 Biotechnological Processes for the Production of High-Added-Value Flavonoids 186

9.4 Future Prospects 191

Acknowledgments 192

References 192

10 Transaminases – A Biosynthetic Route for Chiral Amines 199
Henrike Brundiek and Matthias Höhne

10.1 Introduction 199

10.2 Biocatalysts as Attractive Alternatives to Access Enantiopure Chiral Amines 199

10.3 Transaminases as a Biosynthetic Route for Chiral Amines 201

10.4 Amine Transaminases (ATAs) for the Production of Chiral Amines 203

10.5 Kinetic Resolution and Asymmetric Reductive Amination Using ATAs 207

10.6 Outlook 213

Acknowledgment 214

References 214

11 Biocatalytic Processes for the Synthesis of Chiral Alcohols 219
Gao-Wei Zheng, Yan Ni, and Jian-He Xu

11.1 Introduction 219

11.2 Statin Side Chain 220

11.3 o-Chloromandelic Acid and Its Derivatives 226

11.4 Ethyl 2-Hydroxy-4-phenylbutyrate 229

11.5 Ethyl 4-Chloro-3-hydroxybutanoate 230

11.6 3-Quinuclidinol 232

11.7 3-Hydroxy-3-phenylpropanenitrile 235

11.8 Menthol 237

11.9 Halogen-Substituted 1-Phenylethanol 240

11.10 Summary and Outlook 243

References 244

Part C Reaction and Process Engineering 251

12 Inorganic Adsorbents in Enzymatic Processes 253
Ulrich Sohling, Kirstin Suck, Patrick Jonczyk, Friederike Sander, Sascha Beutel, Thomas Scheper, Axel Thiefes, Ute Schuldt, Claudia Aldenhoven, Gabriella Egri, Lars Dähne, Annamaria Fiethen, Hubert Kuhn, Oliver Wenzel, Heike Temme, Bernd Niemeyer, Paul Bubenheim, and Andreas Liese

12.1 Introduction 253

12.2 Porous Inorganic Adsorbents for Enzyme Purification Processes (Alumina, Aluminosilicates, Precipitated Silica) 259

12.3 Immobilization of Phospholipase A1 and A2 for the Degumming of Edible Oils 265

12.4 Immobilization of Alcohol Dehydrogenase ‘A’ and Candida antarctica Lipase B on Precipitated Silica by Layer-by-Layer-Technology 270

12.5 Molecular Modeling Calculations of the ADH-‘A‘ Immobilization onto Polyelectrolyte Surfaces 273

12.6 Application of Clays and Zeolites for Adsorption of Educts and Products of Reactions with Alcohol Dehydrogenase in Aqueous Reaction Media 278

12.7 Product Separation from Complex Mixtures of Biocatalytic Transformations 283

12.8 Continuous Production and Discontinuous Selective Adsorption of Short-Chain Alcohols in a Fixed-Bed Reactor with Alumina Oxides 287

12.9 Summary and Outlook 290

Acknowledgment 291

References 291

13 Industrial Application of Membrane Chromatography for the Purification of Enzymes 297
Sascha Beutel, Louis Villain, and Thomas Scheper

13.1 Introduction 297

13.2 Membrane Adsorber 298

13.3 Case Studies and Used Model Enzymes 301

13.4 Experimental 302

13.5 Case Study 1: Purification of Penicillin G Amidase 302

13.6 Case Study 2: Purification of Cellulase Cel5A 307

13.7 Case Study 3: Purification of Lipase aGTL 310

13.8 Conclusion and Outlook 313

Acknowledgment 313

References 314

14 Fermentation of Lactic Acid Bacteria: State of the Art and New Perspectives 317
Ralf Pörtner, Rebecca Faschian, and Detlef Goelling

14.1 Introduction 317

14.2 Factors Effecting Growth and Productivity of Lactic Acid Bacteria 322

14.3 Fermentation Techniques for Growth and Production 323

14.4 Case Study: Fixed-Bed Reactor with Immobilized Cells 328

14.5 Conclusions 335

Acknowledgment 336

References 337

15 The Bubble Column Reactor: A Novel Reactor Type for Cosmetic Esters 343
Sören Baum, Jakob J. Mueller, Lutz Hilterhaus, Marrit Eckstein, Oliver Thum, and Andreas Liese

15.1 Introduction 343

15.2 Bubble Column Reactor in Comparison to Other Reactor Types 346

15.3 Case Study: Enzymatic Production of Cosmetic Esters 349

15.4 In situ Online Measurements in a Bubble Column Reactor by Means of Fourier Transformed Mid-Infrared Spectroscopy 357

15.5 Summary and Outlook 364

References 365

16 Pharmaceutical Intermediates by Biocatalysis: From Fundamental Science to Industrial Applications 367
Ramesh N. Patel

16.1 Introduction 367

16.2 Boceprevir: Oxidation of 6,6-Dimethyl-3-azabicyclo[3.1.0]hexane by Monoamine Oxidase 367

16.3 Pregabalin: Enzymatic Preparation of (S)-3-Cyano-5-methylhexanoic Acid Ethyl Ester 369

16.4 Glucagon-Like Peptide-1 (GLP-1): Enzymatic Synthesis of (S)-Amino-3-[3-{6-(2-methylphenyl)} pyridyl]-propionic Acid 371

16.5 Rhinovirus Protease Inhibitor: Enzymatic Preparation of (R)-3-(4-Fluorophenyl)-2-hydroxy Propionic Acid 373

16.6 Saxagliptin: Enzymatic Synthesis of (S)-N-boc-3-Hydroxyadamantylglycine 374

16.7 Sitagliptin: Enzymatic Synthesis of Chiral Amine 375

16.8 Montelukast: Enzymatic Reduction for the Synthesis of Leukotriene D (LTD) 4 Antagonists 377

16.9 Clopidogrel: Enzymatic Preparation of (S)-2-Chloromandelic Acid Esters 378

16.10 Calcitonin Gene-Related Peptide Receptors Antagonist: Enzymatic Preparation of (R)-2-Amino-3-(7-methyl-1 H-indazol-5-yl)propanoic Acid 379

16.11 Chemokine Receptor Modulators: Enzymatic Desymmetrization of Dimethyl Ester 381

16.12 Regioselective Enzymatic Acylation of Ribavirin 383

16.13 Atorvastatin: Enzymatic Preparation of (R)-4-Cyano-3-hydroxybutyrate 384

16.14 Atazanavir, Telaprevir, Boceprevir: Enzymatic Synthesis of (S)-Tertiary-leucine 385

16.15 Relenza (Zanamivir): Enzymatic Synthesis of N-Acetylneuraminic Acid 387

16.16 Atorvastatin, Rosuvastatin: Aldolase-Catalyzed Synthesis of Chiral Lactol Intermediates 389

16.17 Anticancer Drugs: Epothilone B and Microbial Hydroxylation of Epothiolone B 390

16.18 Corticotropin-Releasing Factor-1 (CRF-1) Receptor Antagonist: Enzymatic Synthesis of (S)-1-Cyclopropyl-2-methoxyethanamine 392

16.19 Conclusion 393

Acknowledgment 394

References 395

17 Biocatalysis toward New Biobased Building Blocks for Polymeric Materials 405
Katrien Bernaerts, Luuk Mestrom, and Stefaan DeWildeman

17.1 Introduction 405

17.2 Questions and Answers that Lead Us toward Sustainability in Plastic Materials 406

17.3 Criteria and Qualifiers for New Biobased Building Blocks for Plastics Applications 413

17.4 Criteria and Qualifiers for Launching New Biobased Building Blocks for Plastics Applications in New Value Chains 414

17.5 Position of Biobased Building Blocks Innovation in the Plastics Pyramid 414

17.6 Biocatalysis Conversions and Challenges toward newBBBB 415

17.7 Biocatalytic Cascade Reactions to Functional Building Blocks for Materials 423

17.8 Conclusion 424

References 426

Index 429

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Author Information

Dr. Lutz Hilterhaus carried out his studies of chemistry at the University Münster before moving to Hamburg. Having obtained his PhD from the Hamburg University of Technology (TUHH) in the working group of Prof. Liese in 2008, he spent one year with Prof. Bornscheuer at the University Greifswald before taking up the possibility to start as a Junior Group Leader at the Institute of Technical Biocatalysis at the TUHH. Dr. Lutz Hilterhaus finalized his habilitation in 2016 and has authored over 30 scientific publications and has received the "Karl-Heinz-Ditze Preis für besondere Leistungen in den Ingenieurwissenschaften" in 2008.

Dr. Andreas Liese is Professor at the Hamburg University of Technology, where he is head of the Institute of Technical Biocatalysis. He studied chemistry at the University of Bonn, Germany, and carried out his doctoral research at the Research Center Jülich, Germany. From 1998 to 2003 he was head of the Enzyme Group within the Institute of Biotechnology II (Prof. Dr. C. Wandrey), Research Center Jülich. During a sabbatical in 2000 at Pfizer Global Research & Development, San Diego, USA, he there initiated a R&D group on biocatalysis. From 2003 to 2004 he worked as associate professor at the University of Münster. In 2003 Liese received the Award of Up-and-Coming Teacher in Higher Education in the field of biotechnology (DECHEMA, Germany). Since 2014 he is elected member of the steering committee of the DECHEMA e.V.

Dr. Ulrich Kettling is Global Director and Head of Market Segment Industrial Enzymes at Clariant. Before he was Head of Biotechnology R&D and Global Director Biotechnology and Biorefinery at Clariant and Süd-Chemie. Before joining Süd-Chemie, Dr. Kettling was co-founder and Chief Scientific Officer of Direvo Biotech AG. Dr. Kettling graduated in Biotechnology at the Technical University Braunschweig and obtained his PhD at the Max Planck Institute for Biophysical Chemistry in Göttingen.

Dr. Garabed Antranikian is Professor at the Hamburg University of Technology, where he is head of the Institute of Technical Microbiology. He studied Biology at the American University in Beirut. At the University of Göttingen he completed his PhD in Microbiology in 1980 in the laboratory of Professor Gerhard Gottschalk and qualified as a post-doctoral lecturer (Habilitation) in 1988. In 1989 he was appointed to a professorship in Microbiology at the Hamburg University of Technology. He was president of the International Society for Extremophiles and is chief editor of the scientific journal Extremophiles. In 2004 he was awarded the most prestigious prize for environment protection by the president of the Federal Republic of Germany. Since 2007 he is the coordinator of the "Biocatalysis2021" Cluster and the "Biorefinery2021" Cluster of the Ministry of Education and Research and he is chairman of IBN Industrial Biotechnology North. Since 2011 he is the president of Hamburg University of Technology.
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