Biocatalysis is rapidly evolving into a key technology for the
discovery and production of chemicals, especially in the
pharmaceutical industry, where high yielding chemo-, regio-, and
enantioselective reactions are critical. Taking the latest
breakthroughs in genomics and proteomics into consideration,
Biocatalysis for the Pharmaceutical Industry concisely yet
comprehensively discusses the modern application of biocatalysis to
drug discovery, development, and manufacturing. Written by a team
of leading experts, the book offers deep insight into this cutting
edge field.

* Covers a wide range of topics in a systematic manner with an
emphasis on industrial applications

* Provides a thorough introduction to the latest biocatalysts,
modern expression hosts, state-of-the-art directed evolution, high
throughput screening, and bioprocess engineering

* Addresses frontier subjects such as emerging enzymes,
metabolite profiling, combinatorial biosynthesis, metabolic
engineering, and autonomous enzymes for the synthesis and
development of chiral molecules, drug metabolites, and
semi-synthetic medicinal compounds and natural product analogs

* Highlights the impact of biocatalysis on green chemistry

* Contains numerous graphics to illustrate concepts and
techniques

Biocatalysis for the Pharmaceutical Industry is an
essential resource for scientists, engineers, and R&D policy
makers in the fine chemical, pharmaceutical, and biotech
industries. It is also an invaluable tool for academic researchers
and advanced students of organic and materials synthesis, chemical
biology, and medicinal chemistry.

Dr. Junhua Tao is co-founder and Chief Scientific Officer at
BioVerdant, Inc.USA. He was the Head of the Biotransformation Group
at Pfizer Global R&D from 2000 to 2005. Trained in synthetic
organic chemistry, Dr. Tao has published over 50 papers and serve
as an advisory board member of Engineering in Life Sciences

Prof. Guo-Qiang Lin is a professor at Shanghai Institute
of Organic Chemistry, the Chinese Academy of Sciences, China. With
over 150 publications, Prof. Lin is well recognized in synthetic
organic chemistry and medicinal chemistry. He is associate editors
for three journals in the fields and an Executive Board Member for
Tetrahedron.

Prof. Andreas Liese is Professor of Technical
Biochemistry and Head of Institute of Technical Biocatalysis,
Hamburg University of Technology, Germany. Worked in both academia
and pharmaceutical industry, Prof. Liese has made significant
contributions to industrial biotransformations, enzyme technology
and biochemical engineering. He is a member of the editorial board,
Journal of Molecular Catalysis B and has published over 50 papers
and 2 books.

• Covers a wide range of topics in a systematic manner with an emphasis on industrial applications
• Provides a thorough introduction to the latest biocatalysts, modern expression hosts, state-of-the-art directed evolution, high throughput screening, and bioprocess engineering
• Addresses frontier subjects such as emerging enzymes, metabolite profiling, combinatorial biosynthesis, metabolic engineering, and autonomous enzymes for the synthesis and development of chiral molecules, drug metabolites, and semi-synthetic medicinal compounds and natural product analogs
• Highlights the impact of biocatalysis on green chemistry
• Contains numerous graphics to illustrate concepts and techniques

Biocatalysis for the Pharmaceutical Industry is an essential resource for scientists, engineers, and R&D policy makers in the fine chemical, pharmaceutical, and biotech industries. It is also an invaluable tool for academic researchers and advanced students of organic and materials synthesis, chemical biology, and medicinal chemistry.

1 Enzymes and Their Synthetic Applications: An Overview.

1.1 Introduction.

1.2 Enzyme Families.

1.3 Enzyme Discovery and Optimization.

1.4 Enzyme Production.

1.5 Enzymes and Synthetic Applications.

1.5.1 Ketoreductases (EC 1.1.1.2).

1.5.2 Enoate Reductases or Ene Reductases (EC 1.3.1.16).

1.5.3 Oxygenases (EC. xxxx).

1.5.4 Alcohol Oxidases (EC 1.1.3.X).

1.5.5 Peroxidases (EC 1.11.1.X).

1.5.6 Halogenases (EC. xxxx).

1.5.7 Nitrilases (EC 3.5.5.1).

1.5.8 Nitrile Hydratases (EC 4.2.1.84).

1.5.9 Epoxide Hydrolases (EC 3.3.2.X).

1.5.10 !-Transaminases (EC 2.6.1.X).

1.5.11 Hydroxynitrile Lyases (EC 4.1.2.X).

1.5.12 Aldolases (EC. xxxx).

1.5.13 Glycosidases (EC. xxxx).

1.5.14 Glycosyltransferase (EC. xxxx).

1.6 Conclusions.

2 Expression Hosts for Enzyme Discovery and Production.

2.1 Introduction.

2.2 How to Choose an Expression System.

2.3 Prokaryotic Expression Systems.

2.3.1 Posttranslational Modification in Prokaryotes.

2.3.2 Escherichia coli.

2.3.3 Bacilli.

2.3.4 Pseudomonas fluorescens.

2.3.5 Other Prokaryotic Expression Systems.

2.4 Eukaryotic Expression Systems.

2.4.1 Yeasts.

2.4.2 Filamentous Fungi.

2.4.3 Insect/Baculovirus System.

2.4.4 Mammalian Cell Cultures.

2.4.5 Other Expression Systems.

2.5 Cell-Free Expression Systems.

2.6 Conclusions.

3 Directed Enzyme Evolution and High-Throughput Screening.

3.1 Introduction.

3.2 Directed Evolution Library Creation Strategies.

3.2.1 Random and Semi-Rational Mutagenesis.

3.2.2 Gene Shuffling.

3.3 Directed Evolution Library Screening/Selection Methods.

3.3.1 In Vivo Methods: Genetic Complementation.

3.3.2 In Vivo Methods: Chemical Complementation.

3.3.3 In Vivo Methods: Surface Display.

3.3.4 In Vitro Methods: Lysate Assay.

3.3.5 In Vitro Methods: Ribosome Display.

3.3.6 In Vitro Methods: In Vitro Compartmentalization.

3.3.7 Equipment/Automation.

3.4 Selected Industrial Examples.

3.4.1 Activity.

3.4.2 Thermostability.

3.4.3 Substrate Specificity.

3.4.4 Product Specificity.

3.4.5 Enantioselectivity.

3.5 Conclusions and Future Directions.

4 Applications of Reaction Engineering to Industrial Biotransformations.

4.1 Introduction.

4.2 Metabolic Bioconversion.

4.3 Enzymatic Biotransformations.

4.3.1 Cofactor Regeneration.

4.3.2 Racemic Mixtures.

4.3.3 Equilibrium Conversion.

4.3.4 By-Product Formation.

4.3.5 Substrate Inhibition.

4.3.6 Low Solubility.

4.4 Conclusions.

5 Chiral Synthesis of Pharmaceutical Intermediates Using Oxynitrilases.

5.1 Introduction.

5.2 HNL.

5.2.1 The Natural Function and Distribution of HNLs.

5.2.2 Classification of HNLs.

5.2.3 New HNLs and High-Throughput Screening.

5.3. Reaction of HNLs.

5.3.1 Reaction System.

5.3.2 Immobilization of Enzyme.

5.3.3 Continuous Reactors.

5.3.4 Henry Reaction.

5.4 Transformation of C…