Enzyme Cascade Design and Modelling

✍ Scribed by Selin Kara (editor), Florian Rudroff (editor)

• Publisher: Springer
• Year: 2021
• Tongue: English
• Leaves: 184
• Category: Library

✦ Synopsis

This book provides a comprehensive overview of the recent developments achieved in the field of chemo/enzymatic cascades with topics spanning from design (in vitro and in vivo) to kinetic- and process modelling as well as process control. Opportunities and challenges of building multi-step chemo/enzymatic reactions are discussed, whereby the latter are critically assessed in each chapter and methods to ease the implementation are explored. Both, multi-enzymatic cascades and chemo-enzymatic cascades are presented with the motivation of combining the strengths of these two worlds (e.g. selectivity, activity and robustness) not neglecting the obstacles and challenges of such endeavour. Furthermore, the use of non-conventional media for catalytic cascade reactions, recent achievements and potential for future developments in a technical environment are addressed.

✦ Table of Contents

Preface
Contents
Chapter 1: Introduction
References
Chapter 2: Enzyme Cascade Design: Retrosynthesis Approach
2.1 Introduction
2.1.1 Biocatalytic Retrosynthesis
2.1.2 Enzyme Cascade Design (Biosynthetic)
2.1.3 Enzyme Cascade Design (Synthetic)
2.2 Retrosynthesis to Produce Pathways to the Target Molecule (Step 1)
2.2.1 Manual Retrosynthesis
2.2.2 Moving Towards Automated Biocatalytic Retrosynthesis
2.3 Identifying Enzymes to Fulfil Steps in the Proposed Pathways (Step 2)
2.3.1 Selection of Enzymes Manually by Literature Searches or Enzyme Screening
2.3.2 Selection from Databases Based on Molecular Similarity
2.3.3 Selection Based on Enzyme Structure
2.4 Selection of the Most Promising Pathways (Step 3)
2.5 Experimental Evaluation of Selected Pathways (Step 4)
2.5.1 Build and Test
2.5.2 Analyse
2.6 Conclusions and Outlook
References
Chapter 3: Multi-Enzymatic Cascades In Vitro
3.1 Introduction
3.2 Cascades to Solve Synthetic Problems
3.2.1 Combination of Selective Enzymatic Steps with Isomerizing Reactions
3.2.2 Cascade Reactions for Cofactor Regeneration
3.3 Examples of In Vitro Cascades from Industry
3.4 Conclusion and Outlook
References
Chapter 4: Multi-Enzymatic Cascades In Vivo
4.1 Introduction
4.1.1 Biocatalysis
4.1.2 Biocatalytic Cascade Reactions
4.1.3 In Vivo Cascades
4.2 Enzymatic Cascades In Vivo: Advantages and Challenges
4.2.1 Comparison to In Vitro Systems
4.2.2 What to Consider When Designing a Biocatalytic Cascade in the Whole-Cell
4.2.3 Challenges: What Can Go Wrong
4.2.4 Improvements: How to Tackle these Challenges
4.3 Examples for In Vivo Cascades on the Laboratory Scale
4.4 Examples from Metabolic Engineering: Industrially Applicable Cell Factories
4.5 Conclusion and Prospects
References
Chapter 5: Design and Development of Chemoenzymatic Cascades
5.1 Introduction
5.2 ``Flow Scheme´´ for Developing Chemoenzymatic Cascades
5.3 Studies on Catalyst Compatibilities and Conclusions for the Set-up of One-Pot Processes
5.4 Studies on Undesired Side-Reactions As Well As Unfavored Thermodynamics and Conclusions for the Set-up of One-Pot Processes
5.5 Studies on the Impact of Solvents and Conclusions for the Set-up of One-Pot Processes
5.6 Compartmentalization as a Process Concept to Overcome Hurdles of Incompatibility
5.7 Modeling of Processes
5.8 Conclusions and Outlook
References
Chapter 6: Enzyme Cascade Kinetic Modelling
6.1 Enzyme Kinetic Models and Their Benefits
6.2 Setting-up Conditions of an Enzymatic Cascade System and Kinetic Model Development
6.2.1 Selection of Reaction Conditions
6.2.2 Enzyme Kinetics and Kinetic Model
6.2.2.1 Determination of Kinetic Parameters
6.2.3 Mathematical Model Development and Validation
6.2.4 Model Application
6.3 Conclusions
References
Chapter 7: Enzyme Cascade Reaction Engineering
7.1 Introduction
7.2 Single-Step Enzymatic Catalysis: Reactor Configurations and Operation Mode
7.2.1 Batch-Wise Operated Stirred-Tank Reactor (BSTR)
7.2.2 Continuously Operated Packed-Bed Reactor (CPBR)
7.2.3 Continuously Operated Stirred-Tank Reactor (CSTR)
7.3 Enzymatic Cascade Reactions: Essential Characteristics and Examples of Recent Developments
7.3.1 Enzymatic Cascade Reactions in Continuous Flow
7.3.2 Enzymatic Cascade Reactions in Discontinuous Systems
References
Chapter 8: Enzyme Cascade Process Design and Modelling
8.1 Introduction
8.2 Biocatalytic Cascades
8.3 System Design
8.3.1 Strategic Considerations
8.3.2 Proof-of-Concept Cascade Design
8.3.3 Scalable Cascade Design
8.3.4 Process Design
8.4 The Role of Kinetic Modelling
8.4.1 Introduction
8.4.2 Modelling Modules
8.4.3 Modelling of Complete Cascades
8.5 Remaining Challenges
8.6 Future Perspectives
8.7 Concluding Remarks
References
Chapter 9: Enzyme Cascade Reaction Monitoring and Control
9.1 Introduction
9.1.1 Differentiation of Off-, At-, On-, and Inline Analytics and Chemometric Modelling
9.1.2 Challenges in Monitoring Sequential Reactions, Especially Enzyme Cascades
9.1.3 Resolution and Precision
9.2 Measurement Techniques Being Applied in Biotransformations
9.2.1 Inline Measurement Techniques
9.2.1.1 Infrared Spectroscopy (NIR and MIR)
9.2.1.2 Raman Spectroscopy
9.2.1.3 Measurement of pH
9.2.2 Online Measurement Techniques
9.2.2.1 UV/VIS Spectroscopy
9.2.2.2 Fluorescence Spectroscopy
9.2.2.3 Nuclear Magnetic Resonance Spectroscopy
9.2.3 Atline Measurement Techniques
9.2.4 Suitability of Different Measurement Techniques
9.2.5 General Workflow Generating Inline Analytics
9.3 Aim of Inline Analytics in Reaction Cascades
9.3.1 Real-Time Analysis Enabling Reaction Control
9.3.2 Optimizing Productivity and Quality
References
Chapter 10: Enzymatic Cascade Reactions in Non-Conventional Media
10.1 Introduction
10.2 Chemo-enzymatic Cascades in Non-conventional Media
10.3 Enzymatic Cascades in Non-conventional Media
10.4 Recent Developments
10.5 Conclusions and Future Prospects
References
Chapter 11: Perspectives