Biocatalysis for Practitioners E-Book

• Herausgeber: Wiley-VCH GmbH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 995

Veröffentlichungsjahr: 2021

Beschreibung

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.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

Foreword

Part I: Enzyme Techniques

1 Techniques for Enzyme Purification

1.1 Introduction

1.2 Traditional Enzyme Purification

1.3 Example of a Traditional Enzyme Purification Protocol

1.4 Purification of Recombinant Enzymes

1.5 Column Materials

1.6 Conclusions

References

2 Enzyme Modification

2.1 Introduction

2.2 Practical Approach: Experimental Information, Analytical Methods, Tips and Tricks, and Examples

2.3 Expectations and Perspectives

2.4 Concluding Remarks

References

Note

3 Immobilization Techniques for the Preparation of Supported Biocatalysts: Making Better Biocatalysts Through Protein Immobilization

3.1 Introduction

3.2 General Aspects to Optimize Enzyme Immobilization Protocols

3.3 Type of Carriers for Immobilized Proteins

3.4 Immobilization Methods and Manners

3.5 Evaluation of the Enzyme Immobilization Process

3.6 Applied Examples of Immobilized Enzymes

3.7 Challenges and Opportunities in Enzyme Immobilization

3.8 Conclusions

List of Abbreviations

References

4 Compartmentalization in Biocatalysis

4.1 Introduction

4.2 Cell as a Compartment

4.3 Compartmentalization Using Protein Assemblies

4.4 Compartmentalization Using Emulsion and Micellar Systems

4.5 Compartmentalization Using Encapsulation

4.6 Compartmentalization Using Tea Bags and Thimbles

4.7 Separation of Reaction Steps Using Continuous Flow

4.8 Conclusions and Prospects

References

Part II: Enzymes Handling and Applications

5 Promiscuous Activity of Hydrolases

5.1 Introduction

5.2 Catalytic Promiscuity

5.3 Hydrolases

5.4 Conclusions

References

Note

6 Enzymes Applied to the Synthesis of Amines

6.1 Introduction

6.2 Hydrolases

6.3 Amine Oxidases

6.4 Transaminases (or Aminotransferases)

6.5 Amine Dehydrogenases, Imine Reductases, and Reductive Aminases

6.6 Ammonia Lyases

6.7 Pictet–Spenglerases

6.8 Engineered Cytochrome P450s (Cytochrome “P411”)

6.9 Protocols for Selected Reactions

6.10 Conclusions

Acknowledgments

References

7 Applications of Oxidoreductases in Synthesis: A Roadmap to Access Value-Added Products

7.1 Introduction

7.2 Reductive Processes

7.3 Oxidative Processes

7.4 Protocols for Selected Reactions Employing Oxidoreductases

7.5 Conclusions

Acknowledgments

References

Note

8 Glycosyltransferase Cascades Made Fit For the Biocatalytic Production of Natural Product Glycosides

8.1 Introduction: Glycosylated Natural Products and Leloir Glycosyltransferases

8.2 Glycosylated Flavonoids and Nothofagin

8.3 Glycosyltransferase Cascades for Biocatalytic Synthesis of Nothofagin

8.4 Enzyme Expression

8.5 Solvent Engineering for Substrate Solubilization

8.6 Nothofagin Production at 100 g Scale

8.7 Concluding Remarks

References

Part III: Ways to Improve Enzymatic Transformations

9 Application of Nonaqueous Media in Biocatalysis

9.1 Introduction

9.2 Advantages and Disadvantages of Reactions in Nonaqueous Media

9.3 Nonaqueous Media Used for Biocatalysis

9.4 Enzymatic Activity and Inactivation in Nonaqueous Media

9.5 Practical Approaches to Stabilize Enzymes in Nonaqueous Media

9.6 Examples of Biocatalyzed Reactions in Solvent-Free Systems

9.7 Examples of Reactions in Micro-aqueous Systems

9.8 Examples of Reactions in Bio-Based Liquids

9.9 Examples of Reactions in Liquid CO2

9.10 Examples of Reactions in CO2-Expanded Bio-based Liquids

9.11 Examples of Reactions in Natural Deep Eutectic Solvents

9.12 Conclusions and Future Perspectives

References

10 Nonconventional Cofactor Regeneration Systems

10.1 Introduction

10.2 Basics of Photocatalytic NADH Regeneration

10.3 Advancements in Photocatalytic NADH Regeneration

10.4 Expectations

10.5 Conclusions and Prospects

List of Abbreviations

References

Note

11 Biocatalysis Under Continuous Flow Conditions

11.1 Introduction

11.2 Practical Approach for Biocatalysis Under Continuous Flow Conditions

11.3 Conclusions and Perspective

References

Notes

Part IV: Recent Trends in Enzyme-Catalyzed Reactions

12 Photobiocatalysis

12.1 Introduction

12.2 Oxidative Processes

12.3 Reductive Processes

12.4 Combination of Photooxidation and Enzymatic Transformation

12.5 Summary and Outlook

Abbreviations

References

13 Practical Multienzymatic Transformations: Combining Enzymes for the One-pot Synthesis of Organic Molecules in a Straightforward Manner

13.1 Introduction

13.2 Non-stereoselective Bienzymatic Transformations

13.3 Stereoselective Bienzymatic Transformations

13.4 Multienzymatic Transformations: Increasing Synthetic Complexity

13.5 Summary and Outlook

References

14 Chemoenzymatic Sequential One-Pot Protocols

14.1 Introduction: Theoretical Information and Conceptual Overview

14.2 State of the Art in Sequential Chemoenzymatic One-Pot Synthesis: Selected Examples and Historical Overview About Selected Contributions

14.3 Practical Aspects of the Development of Sequential Chemoenzymatic One-Pot Syntheses

14.4 Conclusions and Outlook

References

Part V: Industrial Biocatalysis

15 Industrial Processes Using Biocatalysts

15.1 Introduction

15.2 Biocatalysis in the Pharmaceutical Industry

15.3 Aspects to Consider for Development of a Biocatalytic Process on Commercial Scale – A Case Study

15.4 Conclusions, Expectations, and Prospects

Acknowledgments

List of Abbreviations

References

Notes

16 Enzymatic Commercial Sources

16.1 Introduction

16.2 European Companies

16.3 American Companies

16.4 Asian Enzyme Suppliers

16.5 Outlook

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Imaginary traditional enzyme purification scheme.

Table 1.2 Ion exchange chromatography of oxidoreductases.

Table 1.3 Purification of 3‐hydroxyphenylacetate 6‐hydroxylase from

Flavobacte

...

Table 1.4 Selection of various commercially available chromatography media.

Chapter 3

Table 3.1 Properties of commercial carriers for protein immobilization.

Table 3.2 Experimental data obtained in the immobilization time course of Gly...

Chapter 5

Table 5.1 Catalytic promiscuity of some enzymes in the aldol reaction between...

Table 5.2 Conversions and diastereoselectivities obtained for the aldol addit...

Chapter 7

Table 7.1 Selection of common ADHs with “Prelog” or “anti-Prelog” selectivity...

Table 7.2 OYE homologs from various sources most frequently applied in the bi...

Table 7.3 Baeyer–Villiger monooxygenases (BVMO) frequently used for biocata...

Chapter 11

Table 11.1 Reactors used for continuous flow synthesis using biocatalysts. Th...

Chapter 14

Table 14.1 Advantages and disadvantages of the chemoenzymatic one-pot synthes...

Chapter 15

Table 15.1 Analysis of residual enzyme, peptide fragments, and single amino a...

Table 15.2 Elements of the control strategy for impurities associated with th...

Chapter 16

Table 16.1 Enzymes supplied by Biocatalysts with applications in food science...

Table 16.2 Some selected examples of the biocatalysts supplied by Enzymicals.

Table 16.3 ADHs and lipases supplied by Evoxx Technologies.

Table 16.4 Some of the enzymes commercialized by GECCO.

Table 16.5 Enzymes supplied by Johnson-Matthey.

Table 16.6 Examples of the enzymatic products supplied by Metgen Oy in the fi...

Table 16.7 Some hydrolytic enzymes commercialized by Novozymes.

Table 16.8 Some of the biocatalysts supplied by Prozomix.

Table 16.9 Screening kits provided by Codexix Inc.

Table 16.10 Selection of biocatalysts supplied by MP Biomedical.

Table 16.11 Selection of biocatalysts provided by Sigma-Aldrich divided by en...

Table 16.12 Selection of biocatalysts that are provided by Worthington Bioche...

Table 16.13 Examples of the enzymes supplied by Amano and their possible appl...

Table 16.14 Hydrolytic enzymes commercialized by Meito Sangyo Co., Ltd.

Table 16.15 Selected enzymes commercialized by Takabio company.

Table 16.16 Selected biocatalysts commercialized by Toyobo Co., Ltd.

List of Illustrations

Chapter 1

Figure 1.1 Enzyme aggregation and proteolytic degradation processes.

Figure 1.2 Example of an SDS‐PAGE gel. (1) Molecular mass markers, (2) cell ...

Figure 1.3 Ammonium sulfate fractionation. In this example, a pilot experime...

Figure 1.4 IEC of isoforms of highly pure 4‐hydroxybenzoate 3‐hydroxylase (P...

Figure 1.5 Gel filtration. (a) Elution profile and (b)

K

AV

vs log

M

r

plot.

Figure 1.6

N

‐(4‐Hydroxybenzoyl)aminohexyl agarose affinity matrix.

Figure 1.7 Preparation and reconstitution of apo‐flavoproteins on Phenyl Sep...

Figure 1.8 Oligomeric state of

Tt

ProDH and its site‐directed mutants. EE: F1...

Chapter 2

Figure 2.1 Overview of the rational enzyme engineering strategy.

Figure 2.2 Kemp elimination reaction and summery of the computational approa...

Figure 2.3 Mechanism of the histidine-catalyzed ester hydrolysis and the ove...

Figure 2.4 Prelog's rule for predicting the outcome of an alcohol dehydrogen...

Figure 2.5 Structure of Subtilisin Carlsberg is shown in surface mode. The t...

Scheme 2.1 Chemoenzymatic route of lactone

3

from (−)-α-pinene

1

. This lacto...

Figure 2.6 The detectable access tunnels in the crystal structures of cytoch...

Chapter 3

Figure 3.1 Scheme of main enzyme immobilization chemistries

.

Figure 3.2 Immobilization chemistry of enzymes on MANAE-agarose. Dashed line...

Figure 3.3 Graphical representation of the time course immobilization of the...

Figure 3.4 Graphical representation of the time course inactivation of GlyDH...

Figure 3.5 Enzyme inactivation with more than one step.

Chapter 4

Scheme 4.1 Examples of concurrent cascade metal-biocatalytic processes. (a) ...

Figure 4.1 Strategies for using cells for compartmentalization of a two-enzy...

Figure 4.2 The incorporation of nano-metallic palladium (Pd) into the core o...

Scheme 4.2 Examples of sequential chemoenzymatic and multienzyme cascades in...

Scheme 4.3 Bioamination of hydrophobic substrates by a compartmentalized ATA...

Scheme 4.4 Practical applications of CAL-B Pickering emulsions (CAL-B@PE): (...

Scheme 4.5 Combination of encapsulated phenolic acid decarboxylase (PAD) wit...

Scheme 4.6 Use of polymersomes to achieve selective transport as a strategy ...

Scheme 4.7 Concurrent enzymatic cascade toward enantiopure diols employing t...

Scheme 4.8 Chemoenzymatic cascades employing PDMS thimbles for compartmental...

Scheme 4.9 Flow separation of a gold-catalyzed oxidation coupled to an enzym...

Scheme 4.10 Continuous flow coupling of an enzymatic decarboxylation mediate...

Scheme 4.11 Chemoenzymatic deracemization of chiral alcohols employing a con...

Chapter 5

Scheme 5.1 Mechanism of the aldol condensation reaction between acetaldehyde...

Scheme 5.2 Enantioselective hydrolysis of glycidyl butyrate by PPL.

Scheme 5.3 Dynamic kinetic resolution in the preparation of the enantiopure ...

Scheme 5.4 Kazlauskas model to explain the enantiopreference of subtilisin e...

Scheme 5.5 Synthesis of enantiopure Ticagrelor precursor catalyzed by lipase...

Scheme 5.6 Hydrolysis reaction of triacylglycerols catalyzed by lipases.

Figure 5.1 Crystallographic structure of the CAL-B lipase (PDB code: 1TCA). ...

Scheme 5.7 General simplified mechanism of lipase-catalyzed ester hydrolysis...

Scheme 5.8 Preparation of the amide intermediate for the synthesis of Saxagl...

Scheme 5.9 Synthesis of 3-arylidenes through a Knoevenagel condensation cata...

Scheme 5.10 Regioselective enzymatic transesterification of Lobucavir cataly...

Scheme 5.11 Mannich reaction catalyzed by lipases. [63], (b) adapted from He...

Scheme 5.12 Synthesis of two-substituted benzimidazoles catalyzed by α-chymo...

Scheme 5.13 Examples of promiscuous reactions on benzaldehyde derivatives ca...

Scheme 5.14 Examples of promiscuous lipase-mediated reactions on α,β-unsatur...

Scheme 5.15 Aldol reaction between 4-nitrobenzaldehyde and acetone catalyzed...

Scheme 5.16 Aldol condensation between

p

-nitrobenzaldehyde with

in situ

gene...

Scheme 5.17 Hemiacetal formation and its stabilization through interaction w...

Figure 5.2 Aldol reaction progress between hexenal and acetone catalyzed by ...

Scheme 5.18 Aldol reaction between 4-cyanobenzaldehyde and cyclohexanone cat...

Chapter 6

Figure 6.1 The most commonly applied enzymes for the synthesis of α-chiral a...

Scheme 6.1 Simplified catalytic mechanism of serine proteases and lipases.

Scheme 6.2 Depiction of a classical kinetic resolution of racemic primary or...

Scheme 6.3 Dynamic kinetic resolution through the combination of a chemocata...

Scheme 6.4 BASF industrial-scale KR of α-methylbenzylamine (

rac

-

1

) catalyzed...

Scheme 6.5 DKR of 1-aminotetralin (

rac

-

3

) toward the synthesis of norsertral...

Scheme 6.6 Simplified catalytic cycle of FAD-dependent amine oxidases.

Scheme 6.7 Classical deracemization of primary, secondary, and tertiary (mai...

Scheme 6.8 Chemoenzymatic synthetic route from tryptamine (

6

) to (

R

)-harmici...

Scheme 6.9 Reversible catalytic cycle of the enzymatic transamination reacti...

Scheme 6.10 Practical approaches to biocatalytic transamination.

Scheme 6.11 One-pot, two-step (separated in time) deracemization of mexileti...

Scheme 6.12 Biocatalytic transamination of bulky–bulky ketones using enginee...

Scheme 6.13 Comparison between the catalytic mechanisms of (a) amine dehydro...

Scheme 6.14 Characterized substrate scope for the reduction of cyclic imines...

Scheme 6.15 Substrate scope of the currently available IReds/RedAms (a) and ...

Scheme 6.16 KR and deracemization of α-chiral amines: (a) combination of an ...

Scheme 6.17 Biocatalytic synthesis of lysine-specific demethylase-1 (LSD1) i...

Scheme 6.18 Biocatalytic asymmetric reductive amination of acetophenone (

14

)...

Scheme 6.19 Simplified depiction of two typical reaction mechanisms of ammon...

Scheme 6.20 Reactivity and substrate scope of ammonia lyases applied in bioc...

Scheme 6.21 Chemoenzymatic synthesis of (

S

)-2-indolinecarboxylic acid ((

S

)-

1

...

Scheme 6.22

E. coli

/aspartase-immobilized cells catalyze the multiton-scale ...

Scheme 6.23 Enzymatic and chemoenzymatic synthesis of toxin A (

24

) and asper...

Scheme 6.24 Catalytic mechanism of the enzymatic Pictet–Spengler reaction.

Scheme 6.25 Typical substrate scope of the available norcoclaurine synthases...

Scheme 6.26 Chemoenzymatic synthesis of (

R

)-harmicine ((

R

)-

8

) using

Rauvolfi

...

Scheme 6.27 Chemoenzymatic synthesis of (

S

)-trolline ((

S

)-

33

) and analogs....

Scheme 6.28 Proposed catalytic cycle for nitrene transfer catalyzed by engin...

Scheme 6.29 Reaction conditions and substrate scope of cytochrome P411

CHA

.

Chapter 7

Scheme 7.1 Strategies to obtain enantiopure molecules using oxidoreductases:...

Scheme 7.2 NAD(P)H regeneration strategies via (i) coupled-substrate approac...

Scheme 7.3 Stereoselective reduction of carbonyl compounds with an alcohol d...

Scheme 7.4 ADH (engineered KRED)-catalyzed reduction of a carbonyl substrate...

Scheme 7.5 Bi-enzymatic sequence toward the formation of a chiral precursor ...

Scheme 7.6 General concept for the dynamic kinetic resolution of α-substitut...

Scheme 7.7 Dynamic reductive kinetic resolution of

rac

-2-(6-methoxynaphthale...

Scheme 7.8 Disproportionation of

rac

-2-arylpropanals catalyzed by horse live...

Scheme 7.9 Redox isomerization of Achmatowicz pyranones to enantiopure γ-hyd...

Scheme 7.10 Mechanism of old yellow enzymes (OYEs) in the asymmetric reducti...

Scheme 7.11 Overview of activated α,β-unsaturated compounds classified accor...

Scheme 7.12 Overview of all possible binding poses for trisubstituted alkene...

Scheme 7.13 Substrate-based stereocontrol via (a) alkene configuration (bior...

Scheme 7.14 Enzyme-based stereocontrol strategies via (a) protein diversity ...

Scheme 7.15 Dynamic kinetic resolution by reduction of

rac

-3-methyl-5-phenyl...

Scheme 7.16 Overview of the reactions of flavin-dependent monooxygenases. (a...

Scheme 7.17 Strategies employed on carbonyl compounds with Baeyer–Villiger m...

Scheme 7.18 Overview of products obtained by (a) kinetic resolution and (b) ...

Scheme 7.19 Overview of products obtained by (a) desymmetrization of prochir...

Scheme 7.20 Selection of well reacting substrates with styrene monooxygenase...

Scheme 7.21 Substrate acceptance of (a) alkane monooxygenase and (b) alkene ...

Scheme 7.22 Range of chiral sulfoxides obtained in optically pure form throu...

Scheme 7.23 Asymmetric sulfoxidation of pyrmetazole to esomeprazole using an...

Scheme 7.24 Selective oxyfunctionalization reactions catalyzed by unspecific...

Chapter 8

Figure 8.1 Structures of natural product glycosides that are of interest for...

Figure 8.2 Retaining (a) and inverting (b) glycosyltransferase reaction. A s...

Scheme 8.1 Parallel cascade reaction for synthesis of nothofagin from phlore...

Figure 8.3 Time course analysis for individual enzymatic reactions catalyzed...

Figure 8.4 Time courses of growth, glycerol consumption, and enzyme formatio...

Figure 8.5 Synthesis of nothofagin in fed-batch reaction. Reaction condition...

Figure 8.6 (a) Chemical structures of cyclodextrins and (b) molecular shape ...

Figure 8.7 Nothofagin synthesis from phloretin suspension that contained phl...

Figure 8.8 Scale-up of nothofagin synthesis from liquid phloretin/2-hydroxyp...

Chapter 9

Figure 9.1 Nonaqueous media for biocatalysis with their more environmentally...

Figure 9.2 Distribution of water and CO

2

molecules on the surface of

Candida

...

Figure 9.3 Protein engineering methods employed to enhance enzyme stability ...

Scheme 9.1 Synthesis of sebacic bicyclocarbonate by CALB

Immo

Plus in a solv...

Figure 9.4 Whole cell expressing ADH and cofactor regenerating enzyme utiliz...

Figure 9.5 Example of cascade reactions conducted in micro-aqueous system: (...

Scheme 9.2 Kinetic resolution of

rac

-1-(2-fluoro-4-iodophenyl)-3-hydroxypyrr...

Scheme 9.3 The synthesis of (

S

)-3-chloro-1-phenylpropanol by asymmetric redu...

Scheme 9.4 Dynamic kinetic resolution to obtain (

S

)-benzoin butyrate.

Scheme 9.5 Reduction of an α-chloroketone by using the Codex KRED screening ...

Scheme 9.6 Novozym 435-catalyzed transesterification of a bulky α-cyclopropy...

Scheme 9.7 Butyraldehyde reduction catalyzed by HLADH in liquid CO

2

with sol...

Scheme 9.8 Gram-scale Novozym 435-catalyzed transesterification of

rac

-1-ada...

Figure 9.6 Relationship between π* and the activity of Novozym 435 in variou...

Scheme 9.9 The comparison between wild-type CALB and CALB Ser105Ala mutant i...

Scheme 9.10 Design of a designer NADES that can be utilized as a cosolvent a...

Chapter 10

Figure 10.1 Molecular structure of nicotinamide adenine dinucleotide cofacto...

Figure 10.2 Schematic illustration of NAD(P)H enzymatic regeneration with (a...

Figure 10.3 Schematic illustration of photocatalytic NADH regeneration.

Figure 10.4 Mechanism of selective hydrogenation of NAD

+

to 1,4-NADH by

Rh

c...

Figure 10.5 (a) Mechanism of photosensitized Zn-porphyrins in NADH photocata...

Figure 10.6 (a) Schematic illustration of phosphorus-doped TiO

2

(P-TiO

2

) in ...

Figure 10.7 (a) Schematic illustration of graphitic C

3

N

4

in NADH photocataly...

Chapter 11

Figure 11.1 Diagram of a CPR reactor. The rotor consists of 21 disks that ar...

Scheme 11.1 Esterification reaction between racemic 1,2-isopropylidene glyce...

Scheme 11.2 Glycerol carbonate synthesis by applying a combination of the bi...

Scheme 11.3 Representation of the continuous flow reaction enzymatic synthes...

Scheme 11.4 Kinetic resolution of racemic 1-phenylethylamine using PEG600 di...

Scheme 11.5 Flow reactor setup in the application of EZiG

3

-AsR for the kinet...

Scheme 11.6 Lipase Novozym

®

435 in the resolution of

rac

-1-(trityloxy)p...

Scheme 11.7 Dynamic kinetic resolution of racemic

N

-Boc-phenylalanine ethyl ...

Scheme 11.8 Asymmetric reduction of prochiral ketones (

21a-j

) and racemic al...

Chapter 12

Scheme 12.1 Common Photocatalysts (PCs).

Scheme 12.2 Common processes involved in radical chemistry.

Scheme 12.3 General scheme for a Photobiocatalyzed Baeyer–Villiger oxidation...

Scheme 12.4 Baeyer–Villiger oxidation with photocatalytic cofactor regenerat...

Scheme 12.5 General procedure for Photoenzymatic alkane hydroxylation.

Scheme 12.6 Mechanism involved in the alkane hydroxylation reaction with

in

...

Scheme 12.7 Alkane hydroxylation catalyzed by peroxygenase involving H

2

O

2

ph...

Scheme 12.8 Photocatalytic recycling system of NADPH for the P450-mediated

O

Scheme 12.9 Biodecarboxylation with photogeneration of hydrogen peroxide.

Scheme 12.10 Biodecarboxylation of fatty acids to obtain 1-alkenes by means ...

Scheme 12.11 General scheme for enzymatic decarboxylation.

Scheme 12.12 Bienzymatic cascade to convert triolein into (

Z

)-heptadec-8-ene...

Scheme 12.13 Photobiocatalytic epoxidation of styrenes.

Scheme 12.14 General scheme of a photobiocatalytic carbonyl reduction.

Scheme 12.15 Photo(bio)chemical regeneration of reduced cofactor for nicotin...

Scheme 12.16 Promiscuous ERED photobiocatalytic enantioselective reduction o...

Scheme 12.17 Asymmetric bioreduction of activated alkenes by ene-reductases ...

Scheme 12.18 Photoregeneration of reduced flavin in ene-reductase-catalyzed ...

Scheme 12.19 Photoregeneration of reduced flavin using metal complexes and c...

Scheme 12.20 Flavocytochrome c3-catalyzed alkene reduction employing photore...

Scheme 12.21 Photobiocatalytic reduction of imines into enantioenriched amin...

Scheme 12.22 Photobiocatalytic cascade for the asymmetric amine synthesis in...

Scheme 12.23 Bioreductive amination of α-ketoglutarate coupled with differen...

Scheme 12.24 Photobiocatalytic enantioselective radical dehalogenation of α-...

Scheme 12.25 Photobiocatalytic enantioselective radical deacetoxylation of α...

Scheme 12.26 Sequential strategies involving photocatalysis and biocatalysis...

Scheme 12.27 Synthesis of chiral amines by photoenzymatic one-pot, two-step ...

Scheme 12.28 Different combined approaches involving photocatalytic and enzy...

Scheme 12.29 Synthesis of chiral 1,3-mercaptoalkanols by photoenzymatic one-...

Chapter 13

Scheme 13.1 (a) Stepwise, (b) cascade, and (c) sequential transformations: S...

Scheme 13.2 Type of cascade processes: (a) linear; (b) orthogonal; (c) paral...

Scheme 13.3 Amination of (a) 7-hydroxyheptanitrile, oct-7-yn-1-ol and (b) ri...

Scheme 13.4 Transformation of cyclohexane-1,4-dione into 4-aminocyclohexanol...

Scheme 13.5 Biocatalytic synthesis of N-alkylated amines using reductive ami...

Scheme 13.6 One-pot hydrolysis, transamination, and decarboxylative Mannich ...

Scheme 13.7 Enzyme-catalyzed synthesis of (a) nonivamide from vanillin in a ...

Scheme 13.8 One-pot combination of P450 monooxygenase-catalyzed hydroxylatio...

Scheme 13.9 Transformation of 2,6-dimethoxy-4-allylphenol into syringaresino...

Scheme 13.10 Synthesis of ethyl (

S

)-3-4-chloro-3-hydroxybutyrate using a hal...

Scheme 13.11 Stereoselective hydrogen-borrowing amination of alcohols using ...

Scheme 13.12 Amination of primary and secondary alcohols combining the

Asp

Re...

Scheme 13.13 Combination of laccase-mediator systems and selective amine tra...

Scheme 13.14 One-pot deracemization of racemic amines combining two enantioc...

Scheme 13.15 Deracemization of benzylisoquinolines by bio-oxidative kinetic ...

Scheme 13.16 Combination of an artificial transfer hydrogenase with a monoam...

Scheme 13.17 Aldolase–transaminase recycling cascade for the synthesis of DH...

Scheme 13.18 Bienzymatic carboligation-transamination sequence for the one-p...

Scheme 13.19 Stepwise formation of all four 4-amino-1-phenylpentan-2-ol ster...

Scheme 13.20 Combination of ene-reductases and amine transaminases for the s...

Scheme 13.21 Telescopic sequence combining ERED and IRED for the production ...

Scheme 13.22 Bienzymatic cascade production of dihydropinidine using the ATA...

Scheme 13.23 Multienzymatic synthesis of chiral 2,5-substituted pyrrolidines...

Scheme 13.24 Alkaloid syntheses by combination of amine transaminases and sy...

Scheme 13.25 Lyases and ADHs for the synthesis of optically active diols: (a...

Scheme 13.26

In situ

generation of aldehydes using an oxidoreductase for the...

Scheme 13.27 Intramolecular C─C bond formation and carbonyl reduction for th...

Scheme 13.28 Stereoselective hydrogen-borrowing conversion of α-substituted ...

Scheme 13.29 Bienzymatic transformations over carvones involving the use of ...

Scheme 13.30 ERED and ADH in sequential one-pot synthesis of γ-butyrolactone...

Scheme 13.31 ADHs and monooxygenases for the asymmetric synthesis of epoxy a...

Scheme 13.32 Redox isomerization of secondary allylic alcohols.

Scheme 13.33 Laccase mediator system and alcohol dehydrogenase-catalyzed bio...

Scheme 13.34 Chemoenzymatic synthesis of (

S

)-tembamide through bienzymatic h...

Scheme 13.35 One-pot cascade synthesis of

L

-tyrosine derivatives combining a...

Scheme 13.36 Dynamic kinetic resolution of serine to produce

L

-noncanonical ...

Scheme 13.37 Deracemization of amino acids using a

D

-amino acid transaminase...

Scheme 13.38 Deracemization or stereoinversion of amino acids using

L

-amino ...

Scheme 13.39 Synthesis via kinetic resolution of β-arylalanines using enzyme...

Scheme 13.40 Sequential synthesis of chiral cyclic γ-oxo esters involving en...

Scheme 13.41 Sequential synthesis of 3-methylcyclohexanol diastereoisomers i...

Scheme 13.42 One-pot syntheses of 2-phenylethanol from cinnamaldehyde (a) an...

Scheme 13.43 One-pot syntheses of phenethylamines and 2-phenylethanols throu...

Scheme 13.44 One-pot nine-step synthesis of benzylamine from

L

-phenylalanine...

Scheme 13.45 Amino alcohol synthesis involving epoxide hydrolase, alcohol de...

Scheme 13.46 Regio- and stereoselective aminohydroxylation of

cis

- and

trans

Scheme 13.47 Three-step stepwise synthesis of (1

S

,3

S

,4

R

)-1,2,3,4-tetrahydroi...

Scheme 13.48 Cascade synthesis of pyrrolidines and piperidines using CAR, AT...

Scheme 13.49 Synthesis of

p

-hydroxyphenyl lactic acid enantiomers starting f...

Scheme 13.50 Two consecutive multienzymatic cascades for the transformation ...

Scheme 13.51 Three-step biocascade for the conversion of the transformation ...

Scheme 13.52 Independent cascades for the synthesis of

D

-phenylglycine in

E.

...

Scheme 13.53 Biocatalytic cascades for the valorization of

L

-phenylalanine....

Chapter 14

Figure 14.1 Conceptual overview about variants of chemoenzymatic one-pot syn...

Scheme 14.1 Combination of a metal-catalyzed hydrogenation and an enzymatic ...

Scheme 14.2 Combination of a Pd-catalyzed Suzuki reaction with an enzymatic ...

Scheme 14.3 Combination of a Pd-catalyzed Heck reaction with an enzymatic ke...

Scheme 14.4 Combination of a Ru-catalyzed metathesis reaction with an enzyma...

Scheme 14.5 Combination of a Rh-catalyzed isomerization of racemic allylic a...

Scheme 14.6 Combination of a Rh-catalyzed heterocoupling of diazoesters with...

Scheme 14.7 Combination of an organocatalytic aldol reaction under neat cond...

Scheme 14.8 Combination of an organocatalytic Mannich reaction with a subseq...

Scheme 14.9 Combination of an organocatalytic oxidation with a subsequent en...

Scheme 14.10 Combination of an organocatalytic oxidation with a subsequent e...

Scheme 14.11 Combination of an organocatalytic oxidation in the presence of ...

Scheme 14.12 Combination of a regio- and diastereoselective epoxidation with...

Scheme 14.13 Combination of an aldol reaction with a homogeneous organocatal...

Scheme 14.14 Combination of a Suzuki cross coupling reaction with a heteroge...

Scheme 14.15 Combination of biocatalytic, organocatalytic, and metal-catalyz...

Scheme 14.16 Combination of two biocatalytic and a chemocatalytic reaction t...

Figure 14.2 Overview about the impact of reaction parameters on the enzyme u...

Chapter 15

Scheme 15.1 Key enzymatic step in the synthesis of pregabalin (

3

).

Scheme 15.2 Synthesis of a precursor of vernakalant (

6

) through an enzymatic...

Scheme 15.3 Synthesis of sitagliptin (

8

) through a biocatalytic transaminati...

Scheme 15.4 Synthesis of esomeprazole (

10

) through BVMO-mediated oxidation....

Scheme 15.5 Synthesis of a precursor of montelukast (

13

) via stereoselective...

Scheme 15.6 Synthesis of boceprevir (

19

) involving an enzymatic desymmetriza...

Scheme 15.7 Development of a transamination reaction for (

R

)-biphenylalanine...

Figure 15.1 Separation of amino acids under the analytical conditions descri...

Guide

Cover Page

Table of Contents

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Biocatalysis for Practitioners

Techniques, Reactions and Applications

Edited by

Gonzalo de Gonzalo

Iván Lavandera

Editors

Prof. Gonzalo de GonzaloUniversidad de SevillaDpto. de Química Orgánicac/ Profesor García González 241012 SevillaSpain

Prof. Iván LavanderaUniversidad de OviedoDpto. de Química Orgánica e InorgánicaAvenida Julián Clavería 833006 OviedoSpain

All books published by WILEY-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

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© 2021 WILEY-VCH, GmbH, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-34683-7ePDF ISBN: 978-3-527-82444-1ePub ISBN: 978-3-527-82445-8oBook ISBN: 978-3-527-82446-5

Cover Design Adam-Design, Weinheim, Germany

Foreword

The application of biocatalysis to chemical processes has had an exponential growth in the past 20 years. Biotransformations provide the central tools in industrial biotechnology because they address the need for processes with less environmental impact in terms of energy, raw materials, and waste production. Over the past few years, the use of enzymes as biocatalysts for the introduction of enantiopure active compounds has become an established manufacturing process in the specialty and pharmaceutical industry. It has demonstrated that synthetic and computational tools can be exploited to generate new biocatalysts with novel structure and chemical properties. The employment of biocatalysts is attractive for synthetic organic chemists for producing optically active molecules.

In the present book “Biocatalysis for Practitioners,” the authors have attempted to cover some of the most challenging areas in practical enzymatic catalysis through 16 interesting chapters by different specialists of recognized prestige in their field. In my opinion, it is important to recognize the work that the editors have carried out to cover in five sections the most current trends in the field of biocatalysis, which makes this work very useful not only for researchers in this field but also for students who are beginning to understand biocatalysis, so it can be a good textbook for some careers.

The first section consists of four chapters where different techniques to improve and discover new biocatalysts are described. Thus, purification, modification, immobilization, and compartmentalization techniques are treated in each of the chapters with great success, updating the reader on the progress of the different methodologies.

The second section also consists of four chapters of varied themes whose general title is Enzymes Handling and Applications. The fifth chapter tries to explain formal aspects of the so-called catalytic promiscuity, where processes that in principle were difficult to imagine can be nowadays catalyzed by different biocatalysts. Enzymes applied to the synthesis of amines, some applications of oxidoreductases, and the use of glycosyltransferases for the preparation of glycosides are the other chapters of this part.

Recently, many efforts are aimed to optimize the different biocatalytic processes by modifying the reaction medium or improving the recycling of the cofactor. Thus, in Section 3, entitled Ways to Improve Enzymatic Transformations, three very interesting reviews are described on topics of great importance, such as Application of nonaqueous media in biocatalysis, non-conventional cofactor regeneration systems, and Biocatalysis under continuous flow conditions.

A vision of current trends and evolution in synthetic aspects of biotransformations can be found in Section 4 with three chapters, where we can verify the usefulness of photobiocatalysis, multienzymatic transformations, and finally an interesting subject as chemoenzymatic sequential protocols.

To end this interesting book, in the fifth part, two chapters that deal with the increasing possibilities that biocatalysis has in the industry make a very successful closing of this work, on the one hand check the possibilities and the growth of enzymatic catalysis in industrial processes to end with a review of the editors of the book with a very practical chapter, where researchers and industrial sectors can go to check which biocatalysts are commercially available.

Finally, for the subscriber of this prologue, it is an honor to be able to verify how two excellent researchers and people such as Drs Lavandera and de Gonzalo, for whom I was their supervisor of their doctoral theses, have evolved in an extraordinary way with great work since they started their studies, with postdoctoral stays and today with a permanent position at the Universities of Oviedo and Seville. They are doing a great job. For me, it is a great satisfaction to be able to see how the disciples have overcome the teacher.

Vicente Gotor

Professor Emeritus and Ex-Rector of the University of Oviedo (Spain)

Part IEnzyme Techniques