Applied Biocatalysis

John Whittall, PhD, works at the Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture (CoEBio3), Manchester Institute of Biotechnology, University of Manchester, UK. Peter W. Sutton, PhD, was Scientific Investigator, GlaxoSmithKline Research and Development Limited, UK, now R&D Director at GlycoScience S.L., Barcelona, Spain.

• Abbreviations xi1 Directed Evolution of Enzymes Driving Innovation in API Manufacturing at GSK 11.1 Introduction 11.2 Drug Development Stages 31.3 Enzyme Panels 61.4 Enzyme Engineering 101.5 Case Studies 181.6 Outlook 222 Survey of Current Commercial Enzyme and Bioprocess Service Providers 272.1 Commercial Enzyme Suppliers/Distributors 282.2 Bioprocess Service Providers 922.3 Chemical Transformations of Selected Commercially Available Enzymes 1033 Imine Reductases 1353.1 Imine Reductase-Catalysed Enantioselective Reductive Amination for the Preparation of a Key Intermediate to Lysine-Specific Histone Demethylase 1 (LSD1) Inhibitor GSK2879552 1353.2 Expanding the Collection of Immine Reductases Towards a Stereoselective Reductive Amination 1383.3 Asymmetric Synthesis of the Key Intermediate of Dextromethorphan Catalysed by an Imine Reductase 1433.4 Identification of Imine Reductases for Asymmetric Synthesis of 1-Aryl-Tetrahydroisoquinolines 1483.5 Preparation of Imine Reductases at 15 L Scale and Their Application in Asymmetric Piperazine Synthesis 1563.6 Screening of Imine Reductases and Scale-Up of an Oxidative Deamination of an Amine for Ketone Synthesis 1624 Transaminases 1654.1 A Practical Dynamic Kinetic Transamination for the Asymmetric Synthesis of the CGRP Receptor Antagonist Ubrogepant 1654.2 Asymmetric Biosynthesis of L-Phosphinothricin by Transaminase 1684.3 Application of In Situ Product Crystallisation in the Amine Transaminase from Silicibacter pomeroyi-Catalysed Synthesis of (S)-1-(3-Methoxyphenyl)ethylamine 1734.4 Enantioselective Synthesis of Industrially Relevant Amines Using an Immobilised ω-Transaminase 1784.5 Amination of Sugars Using Transaminases 1824.6 Converting Aldoses into Valuable ω-Amino Alcohols Using Amine Transaminases 1875 Other Carbon–Nitrogen Bond-Forming Biotransformations 1935.1 Biocatalytic N-Acylation of Anilines in Aqueous Media 1935.2 Enantioselective Enzymatic Hydroaminations for the Production of Functionalised Aspartic Acids 1965.3 Biocatalytic Asymmetric Aza-Michael Addition Reactions and Synthesis of L-Argininosuccinate by Argininosuccinate Lyase ARG4-Catalysed Aza-Michael Addition of L-Arginine to Fumarate 2045.4 Convenient Approach to the Biosynthesis of C2,C6-Disubstituted Purine Nucleosides Using E. coli Purine Nucleoside Phosphorylase and Arsenolysis 2115.5 Production of L- and D-Phenylalanine Analogues Using Tailored Phenylalanine Ammonia-Lyases 2155.6 Asymmetric Reductive Amination of Ketones Catalysed by Amine Dehydrogenases 2215.7 Utilisation of Adenylating Enzymes for the Formation of N-Acyl Amides 2316 Carbon–Carbon Bond Formation or Cleavage 2376.1 Improved Enzymatic Method for the Synthesis of (R)-Phenylacetyl Carbinol 2376.2 Tertiary Alcohol Formation Catalysed by a Rhamnulose-1-Phosphate Aldolase : Dendroketose-1-Phosphate Synthesis 2416.3 Easy and Robust Synthesis of Substituted L-Tryptophans with Tryptophan Synthase from Salmonella enterica 2476.4 Biocatalytic Friedel–Crafts-Type C-Acylation 2506.5 MenD-Catalysed Synthesis of 6-Cyano-4-Oxohexanoic Acid 2566.6 Production of (R)-2-(3,5-Dimethoxyphenyl)propanoic Acid Using an Aryl Malonate Decarboxylase from Bordetella bronchiseptica 2597 Reductive Methods 2637.1 Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High-pH Dynamic Kinetic Reduction 2637.2 Synthesis of a GPR40 Partial Agonist Through a Kinetically Controlled Dynamic Enzymatic Ketone Reduction 2657.3 Lab-Scale Synthesis of Eslicarbazepine 2677.4 Direct Access to Aldehydes Using Commercially Available Carboxylic Acid Reductases 2707.5 Preparation of Methyl (S)-3-Oxocyclohexanecarboxylate Using an Enoate Reductase 2778 Oxidative Methods 2818.1 Macrocyclic Baeyer–Villiger Monooxygenase Oxidation of Cyclopentadecanone on 1 L Scale 2818.2 Regioselective Lactol Oxidation with O2 as Oxidant on 1 L Scale Using Alcohol Dehydrogenase and NAD(P)H Oxidase 2868.3 Synthesis of (3R)-4-[2-Chloro-6-[[(R)-Methylsulphinyl]methyl]-Pyrimidin-4-yl]-3-Methyl-Morpholine Using BVMO-P1-D08 2918.4 Oxidation of Vanillyl Alcohol to Vanillin with Molecular Oxygen Catalysed by Eugenol Oxidase on 1 L Scale 2958.5 Synthesis of Syringaresinol from 2,6-Dimethoxy-4-Allylphenol Using an Oxidase/Peroxidase Enzyme System 3018.6 Biocatalytic Preparation of Vanillin Catalysed by Eugenol Oxidase 3088.7 Vanillyl Alcohol Oxidase-Catalysed Production of (R)-1-(4′-Hydroxyphenyl) Ethanol 3128.8 Enzymatic Synthesis of Pinene-Derived Lactones 3198.9 Enzymatic Preparation of Halogenated Hydroxyquinolines 3269 Hydrolytic and Dehydratase Enzymes 3339.1 Synthesis of (S)-3-(4-Chlorophenyl)-4-Cyanobutanoic Acid by a Mutant Nitrilase 3339.2 Nitrilase-Mediated Synthesis of a Hydroxyphenylacetic Acid Substrate via a Cyanohydrin Intermediate 3379.3 Production of (R)-2-Butyl-2-Ethyloxirane Using an Epoxide Hydrolase from Agromyces mediolanus 3399.4 Preparation of (S)-1,2-Dodecanediol by Lipase-Catalysed Methanolysis of Racemic Bisbutyrate Followed by Selective Crystallisation 3449.5 Biocatalytic Synthesis of n-Octanenitrile Using an Aldoxime Dehydratase from Bacillus sp. OxB-1 3499.6 Access to (S)-4-Bromobutan-2-ol through Selective Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase 35410 Glycosylation, Sulphation and Phosphorylation 36310.1 Rutinosidase Synthesis of Glycosyl Esters of Aromatic Acids 36310.2 Biocatalytic Synthesis of Kojibiose Using a Mutant Transglycosylase 36910.3 Biocatalytic Synthesis of Nigerose Using a Mutant Transglycosylase 37710.4 Easy Sulphation of Phenols by a Bacterial Arylsulphotransferase 38110.5 Shikimate Kinase-Catalysed Phosphorylations and Synthesis of Shikimic Acid 3-Phosphate by AroL-Catalysed Phosphorylation of Shikimic Acid 38610.6 Kinase-Catalysed Phosphorylations of Ketohexose Phosphates and LacC-Catalysed Synthesis of D-Tagatose 1,6-Diphosphate Lithium Salt 39310.7 Kinase-Catalysed Phosphorylations of Xylulose Substrates and Synthesis of Xylulose-5-Phosphate Enantiomers 39710.8 Phosphoramidates by Kinase-Catalysed Phosphorylation and Arginine Kinase-Catalysed Synthesis of Nω-Phospho-L-Arginine 40111 Enzymatic Cascades 40911.1 Redox-Neutral Ketoreductase and Imine Reductase Enzymatic Cascade for the Preparation of a Key Intermediate of the Lysine-Specific Histone Demethylase 1 (LSD1) Inhibitor GSK2879552 40911.2 Asymmetric Synthesis of α-Amino Acids through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids 41311.3 Enantioselective, Catalytic One-Pot Synthesis of γ-Butyrolactone-Based Fragrances 42011.4 Synthesis of Six out of Eight Carvo-Lactone Stereoisomers via a Novel Concurrent Redox Cascade Starting from (R)-and (S)-Carvones 42611.5 One-Pot Biocatalytic Synthesis of D-Tryptophan Derivatives from Substituted Indoles and L-Serine 43511.6 Escherichia coli Lysate Multienzyme Biocatalyst for the Synthesis of Uridine-5’-Triphosphate from Orotic Acid 4 and Ribose 1 44111.7 Aerobic Synthesis of Aromatic Nitriles from Alcohols and Ammonia Using Galactose Oxidase 44911.8 Hydrogen-Borrowing Conversion of Alcohols into Optically Active Primary Amines by Combination of Alcohol Dehydrogenases and Amine Dehydrogenases 45511.9 Ene-Reductase-Mediated Reduction of C=C Double Bonds in the Presence of Conjugated C≡C Triple Bonds: Synthesis of (S)-2-Methyl-5-Phenylpent-4-Yn-1-Ol 46812 Chemo-Enzymatic Cascades 47512.1 Synergistic Nitroreductase/Vanadium Catalysis for Chemoselective Nitroreductions 47512.2 Chemo-Enzymatic Synthesis of (S)-1,2,3,4-Tetrahydroisoquinoline Carboxylic Acids Using D-Amino Acid Oxidase 48212.3 Amine Oxidase-Catalysed Deracemisation of (R,S)-4-Cl-Benzhydrylamine into the (R)-Enantiomer in the Presence of a Chemical Reductant 48812.4 Asymmetric Synthesis of 1-Phenylpropan-2-Amine from Allylbenzene through a Sequential Strategy Involving a Wacker–Tsuji Oxidation and a Stereoselective Biotransamination 49712.5 Chemoenzymatic Synthesis of (2S,3S)-2-Methylpyrrolidin-3-Ol 50413 Whole-Cell Procedures 50913.1 Semipreparative Biocatalytic Synthesis of (S)-1-Amino-1-(3’-Pyridyl)methylphosphonic Acid 50913.2 Practical and User-Friendly Procedure for the Regio- and Stereoselective Hydration of Oleic, Linoleic and Linolenic Acids, Using Probiotic Lactobacillus Strains as Whole-Cell Biocatalysts 51513.3 Clean Enzymatic Oxidation of 12α-Hydroxysteroids to 12-Oxo-Derivatives Catalysed by Hydroxysteroid Dehydrogenase 52113.4 Whole-Cell Biocatalysis Using PmlABCDEF Monooxygenase and Its Mutants: A Versatile Toolkit for Selective Synthesis of Aromatic N-Oxides 528Index 535