Contents
Cover
Related Titles
Title Page
Copyright
Preface
List of Contributors
Chapter 1: Development of Sustainable Biocatalytic Reduction Processes for Organic Chemists
1.1 Introduction
1.2 Biocatalytic Reductions of C=O Double Bonds
1.3 Biocatalytic Reductions of C=C Double Bonds
1.4 Biocatalytic Reductions of Imines to Amines
1.5 Biocatalytic Reductions of Nitriles to Amines
1.6 Biocatalytic Deoxygenation Reactions
1.7 Emerging Reductive Biocatalytic Reactions
1.8 Reaction Engineering for Biocatalytic Reduction Processes
1.9 Summary and Outlook
References
Chapter 2: Reductases: From Natural Diversity to Established Biocatalysis and to Emerging Enzymatic Activities
2.1 Reductases: Natural Occurrence and Context for Biocatalysis
2.2 Emerging Cases of Reductases in Biocatalysis
2.3 Concluding Remarks
References
Chapter 3: Synthetic Strategies Based on C=C Bioreductions for the Preparation of Biologically Active Molecules
3.1 Introduction
3.2 Bioreduction of α,β-Unsaturated Carbonyl Compounds
3.3 Bioreduction of Nitroolefins
3.4 Bioreduction of α,β-Unsaturated Carboxylic Acids and Derivatives
3.5 Bioreduction of α,β-Unsaturated Nitriles
3.6 Concluding Remarks
References
Chapter 4: Synthetic Strategies Based on C=O Bioreductions for the Preparation of Biologically Active Molecules
4.1 Introduction
4.2 Synthesis of Biologically Active Compounds through C=O Bioreduction
4.3 Other Strategies to Construct Biologically Active Compounds
4.4 Summary and Outlook
References
Chapter 5: Protein Engineering: Development of Novel Enzymes for the Improved Reduction of C=C Double Bonds
5.1 Introduction
5.2 The Protein Engineering Process and Employed Mutagenesis Methods
5.3 Examples of Rational Design of Old Yellow Enzymes
5.4 Evolving Old Yellow Enzymes (OYEs)
5.5 Conclusions and Perspectives
References
Chapter 6: Protein Engineering: Development of Novel Enzymes for the Improved Reduction of C=O Double Bonds
6.1 Introduction
6.2 Detailed Characterization of PAR
6.3 Detailed Characterization of LSADH
6.4 Engineering of PAR for Increasing Activity in 2-Propanol/Water Medium
6.5 Application of Whole-Cell Biocatalysts Possessing Mutant PARs and LSADH
6.6 Engineering of β-Keto Ester Reductase (KER) for Raising Thermal Stability and Stereoselectivity
6.7 New Approach for Engineering or Obtaining Useful ADHs/Reductases
References
Chapter 7: Synthetic Applications of Aminotransferases for the Preparation of Biologically Active Molecules
7.1 Introduction
7.2 Applications
7.3 Challenges
7.4 Future Research Needs
7.5 Conclusions
References
Chapter 8: Strategies for Cofactor Regeneration in Biocatalyzed Reductions
8.1 Introduction: NAD(P)H as the Universal Reductant in Reduction Biocatalysis
8.2 The Most Relevant Cofactor Regeneration Approaches – and How to Choose the Most Suitable One
8.3 Coupling the Reduction Reaction to a Regeneration Reaction Producing a Valuable Compound
8.4 Avoiding NAD(P)H: Does It Also Mean Avoiding the Challenge?
8.5 Conclusions
References
Chapter 9: Solvent Effects in Bioreductions
9.1 Introduction
9.2 Solvent Systems for Biocatalytic Reductions
9.3 Solvent Control of Enzyme Selectivity
9.4 Concluding Remarks
References
Chapter 10: Application of In situ Product Removal (ISPR) Technologies for Implementation and Scale-Up of Biocatalytic Reductions
10.1 Introduction
10.2 Process Requirements for Scale-Up
10.3 Bioreduction Process Engineering
10.4 In situ Product Removal
10.5 Biocatalyst Format
10.6 Selected Examples
10.7 Future Outlook
10.8 Conclusions
References
Chapter 11: Bioreductions in Multienzymatic One-Pot and Cascade Processes
11.1 Introduction
11.2 Coupled Oxidation and Reduction Reactions
11.3 Consecutive and Cascade One-Pot Reductions
11.4 Cascade Processes Including Biocatalyzed Reductive Amination Steps
11.5 Other Examples of Multienzymatic Cascade Processes, Including Bioreductive Reactions
References
Chapter 12: Dynamic Kinetic Resolutions Based on Reduction Processes
12.1 Introduction
12.2 Cyclic Compounds
12.3 Acyclic α-Substituted-β-Keto Esters and 2-Substituted-1,3-Diketones
12.4 Acyclic Ketones and Aldehydes
12.5 Conclusions
References
Chapter 13: Relevant Practical Applications of Bioreduction Processes in the Synthesis of Active Pharmaceutical Ingredients
13.1 Introduction
13.2 Ketoreductases
13.3 Ene Reductases
13.4 Others
13.5 Bioreduction-Supported Processes
13.6 Outlook
Acknowledgments
References
Index
Related Titles
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Preface
Since the last decade, chemical industry has been showing a continuous and urgent need for the development of sustainable manufacturing processes, with the reduction of greenhouse gas emission and waste output and replacement of toxic and/or dangerous reagents. Process chemists have turned their attention to the employment of enzyme catalysis in the development of synthetic procedures, especially for the preparation of high-value products in the life science area, such as biologically active molecules and active pharmaceutical ingredients. Efforts have been devoted to optimize biotechnological tools for organic synthesis and to investigate the efficiency and the substrate specificity of biocatalyzed reactions in order to make them a first choice in practical synthetic applications.
This book is intended to describe the state of the art of these efforts for the advantage of both the academic and the industrial audience. The book will focus on the current available toolbox of biocatalyzed reductions of C=O, C=C, and formal C=N double bonds, in order to show (i) which are the reliable biocatalyzed transformations to be used by organic chemists involved in the development of manufacturing processes, and (ii) which are the biotransformations still requiring improvements and investigations. Bioreductions have been chosen as the main topic of the book, because of their widespread applications in organic synthesis and their versatility in the creation of stereogenic centers in chiral molecules.
Chapters 1 and 2 will give an overview of the advantages of enzyme-catalyzed reductions and of the efforts devoted to investigate the emerging enzyme-reducing capabilities. Chapters 3 and 4 will present the synthetic strategies that are currently available for the reduction of C=C and C=O double bonds by means of whole-cell catalysts and isolated enzymes. Chapters 5 and 6 will describe the improvements achieved up to now for these two kinds of bioreduction by manipulation of the enzymes, according to the different approaches of protein engineering. These chapters will show the versatility that is currently possible in adapting the enzymes to the requests of organic synthesis. Chapter 7 will give a survey of the application of the process of enzymatic reductive amination catalyzed by transaminases for the preparation of chiral amines.
Chapters 8–12 will present the improvements brought about by the optimization of reaction conditions (e.g., the choice of the cofactor regeneration system, the nature of the solvent, and the employment of in situ product removal technologies) and the use of particular synthetic procedures (e.g., multienzymatic one-pot and cascade reactions or dynamic kinetic resolution methods).
Finally, Chapter 13 will describe the actual practical applications of bioreductions for the synthesis of important types of biologically active molecules.
Elisabetta Brenna
Politecnico di Milano
Dipartimento di Chimica
Materiali ed Ingegneria Chimica
Milano
Italy
List of Contributors
Elisabetta Brenna
Politecnico di Milano
Via Mancinelli 7
20131 Milano
Italy
Aníbal Cuetos
University of Oviedo
Departamento de Química Orgánica e Inorgánica
c/Julian Claveria 8
33006 Oviedo
Spain
Pablo Domínguez de María
RWTH Aachen University
Institut für Technische und Makromolekulare Chemie (ITMC)
Worringer Weg 1
52074 Aachen
Germany
Alba Díaz-Rodríguez
University of Oviedo
Departamento de Química Orgánica e Inorgánica
c/Julian Claveria 8
33006 Oviedo
Spain
Elena Fernández-Álvaro
GlaxoSmithKline
Diseases of the Developing World Medicines Development Campus
Parque Tecnológico de Madrid
c/Severo Ochoa, 2
28760 Tres Cantos
Spain
Erica E. Ferrandi
Istituto di Chimica del Riconoscimento Molecolare, CNR
Via Mario Bianco 9
20131 Milano
Italy
Francesco G. Gatti
Politecnico di Milano
Dipartimento di Chimica
Materiali e Ingegneria Chimica “Giulio Natta”
Via Mancinelli 7
20131 Milano
Italy
Mélanie Hall
University of Graz
Department of Chemistry
Organic and Bioorganic Chemistry
Heinrichstraße 28
8010 Graz
Austria
Frank Hollmann
Delft University of Technology
Department of Biotechnology
Julianalaan 136
2628BL Delft
The Netherlands
Nobuya Itoh
Toyama Prefectural University
Biotechnology Research Center and
Department of Biotechnology
Kurokawa 5180
Imizu
Toyama 939-0398
Japan
Dimitris Kalaitzakis
University of Crete
Department of Chemistry
Heraklion-Voutes Campus
Heraklion
71003 Crete
Greece
Sanjay Kamat
Hospira Inc.
215 North Field Drive, Bldg. H3-3N
Lake Forest
IL 60045
USA
Selin Kara
Delft University of Technology
Department of Biotechnology
Julianalaan 136
2628BL Delft
The Netherlands
Sabrina Kille
Max-Planck-Institut für Kohlenforschung
Kaiser-Wilhelm-Platz 1
45470 Mülheim an der Ruhr
Germany
and
Department of Chemistry
Philipps-University Marburg
Hans-Meerwein-Strasse
35032 Marburg
Germany
Iván Lavandera
University of Oviedo
Departamento de Química Orgánica e Inorgánica
c/Julian Claveria 8
33006 Oviedo
Spain
Yoshihide Makino
Toyama Prefectural University
Biotechnology Research Center and
Department of Biotechnology
Kurokawa 5180
Imizu
Toyama 939-0398
Japan
Daniela Monti
Istituto di Chimica del Riconoscimento Molecolare, CNR
Via Mario Bianco 9
20131 Milano
Italy
Abraham R. Mártin-García
Universidad de Sonora
Departamento de Ingeniería Química y Metalurgia
Blvd. Luis Encinas y Rosales S/N
Hermosillo
Sonora 83000
México
Yan Ni
East China University of Science and Technology
State Key Laboratory of Bioreactor Engineering
Laboratory of Biocatalysis and Synthetic Biotechnology
Meilong Road 130
Shanghai 200237
China
Sachin Pannuri
Agennix Ag
101 College Road East
Princeton
NJ 08540
USA
Fabio Parmeggiani
Politecnico di Milano
Dipartimento di Chimica
Materiali e Ingegneria Chimica “Giulio Natta”
Via Mancinelli 7
20131 Milano
Italy
Manfred T. Reetz
Max-Planck-Institut für Kohlenforschung
Kaiser-Wilhelm-Platz 1
45470 Mülheim an der Ruhr
Germany
and
Department of Chemistry
Philipps-University Marburg
Hans-Meerwein-Strasse
35032 Marburg
Germany
Alessandro Sacchetti
Politecnico di Milano
Dipartimento di Chimica
Materiali e Ingegneria Chimica “Giulio Natta”
Via Mancinelli 7
20131 Milano
Italy
Joerg H. Schrittwieser
Delft University of Technology
Department of Biotechnology
Julianalaan 136
2628BL Delft
The Netherlands
Ioulia Smonou
University of Crete
Department of Chemistry
Heraklion-Voutes Campus
Heraklion
71003 Crete
Greece
Gábor Tasnádi
University of Graz
ACIB GmbH c/o
Organic and Bioorganic Chemistry
Heinrichstraße 28
8010 Graz
Austria
Roland Wohlgemuth
Sigma-Aldrich Chemie GmbH
Industriestrasse 25
9470 Buchs
Switzerland
John M. Woodley
Technical University of Denmark
Department of Chemical and Biochemical Engineering
Center for Process Engineering and Technology
Søltofts Plads
2800 Lyngby
Denmark
Jian-He Xu
East China University of Science and Technology
State Key Laboratory of Bioreactor Engineering
Laboratory of Biocatalysis and Synthetic Biotechnology
Meilong Road 130
Shanghai 200237
China
Hui-Lei Yu
East China University of Science and Technology
State Key Laboratory of Bioreactor Engineering
Laboratory of Biocatalysis and Synthetic Biotechnology
Meilong Road 130
Shanghai 200237
China
