Microbial Production of High-Value Products

Contents
Advancements in Inducer Systems for Recombinant Protein Production in E. coli
1 Tuning Recombinant Protein Production in E. coli
2 Promoter Systems of E. coli
3 Inducer Systems in E. coli
3.1 Lactose Induction System
3.2 Arabinose Induction System
3.3 Rhamnose Induction System
3.4 pNEW Induction System
4 Conclusions and Future Trends
References
Microbial Biosynthesis of Straight-Chain Aliphatic Carboxylic Acids
1 Overview
2 Biosynthesis of Straight-Chain Aliphatic Carboxylic Acids
2.1 C1 Formic Acid
2.2 C2 Acetic Acid
2.3 C3 Propionic Acid
2.4 C4 (1) Butyric Acid
2.5 C4 (2) Isobutyric Acid
2.6 C5 Valeric Acid
2.7 C6 (1) Caproic Acid
2.8 C6 (2) Adipic Acid
2.9 C7 Heptanoic Acid
2.10 Medium-Chain Straight Aliphatic Carboxylic Acids
2.10.1 Medium-Chain Fatty Acids
2.10.2 Medium-Chain Dicarboxylic Acids
2.11 Long Straight-Chain Aliphatic Carboxylic Acids
2.11.1 Long-Chain Fatty Acids (>C12)
2.11.2 Long-Chain Dicarboxylic Acids
3 The Challenges and Future Directions
3.1 Product Toxicity
3.2 Genetic Engineering Tools for Microbial Biosynthesis
3.3 Efficiency of the Biosynthesis Pathways
4 Concluding Remarks
References
Microbial Production of Amines and Amino Acids by Fermentation
1 Introduction
2 New Technological Developments for Production of Proteinogenic Amino Acids
3 Non-Proteinogenic Amino Acids
3.1 γ-Aminobutyrate (GABA)
3.2 5-Aminovalerate (5AVA)
3.3 Halogenated Tryptophan
3.4 l-Ornithine
3.5 ε-Aminolevulinic Acid (5-ALA)
3.6 l-Pipecolic Acid
3.7 Ectoine and Hydroxyectoine
3.8 l-Theanine
4 N-Alkylation of Amino Acids
4.1 DpkA Derived Alkylation
4.2 SAM-Dependent Methylation
4.3 N-Hydroxylation
4.4 N-Acetylation
5 Diamines
5.1 Cadaverine (1,5-Diaminopentane)
5.2 Putrescine (1,4-Diaminobutane)
5.3 1,3-Diaminopropane
5.4 1,6-Diaminohexane
6 Concluding Remarks and Outlook
References
Strategies for Improving Biotherapeutic Protein Production in Microbial Cell Factories
1 Introduction
2 Heterologous Protein Expression
3 Role of Molecular Biology
3.1 Cloning Strategies
3.2 Codon Optimization
3.3 Host Selection
3.4 Plasmids
3.4.1 Origin of Replication
3.4.2 Promoter
3.4.3 Ribosome Binding Site (RBS)
3.4.4 Protein Tags, Molecular Chaperone, Affinity Tags, and Signal Sequences
3.4.5 Selectable Marker
4 Upstream Process Development Approach
4.1 Medium Screening and Optimization
4.2 Process Parameter Optimization
4.2.1 Temperature
4.2.2 pH
4.2.3 Inducer Concentration and Induction Phase
4.2.4 Dissolved Oxygen (DO)
4.2.5 Dissolved Carbon Dioxide (CO2)
4.2.6 Pressure
4.2.7 Redox Potential
4.2.8 Ionic Strength
4.2.9 Culture Volume
4.2.10 Foam
5 Conclusions and Future Perspective
References
Current Trends and Prospects in Antimicrobial Peptide Bioprocessing
1 Introduction
2 Antimicrobial Peptides
2.1 Properties
2.2 Mechanisms of Action and Targets
2.3 Classification
3 Upstream Process Development
3.1 Recombinant AMP Production in Microbial Cells
3.2 Strategies to Enhance the Heterologous Expression Level
3.2.1 Cell Line Engineering and Host Strain
3.2.2 Promoters and Codon Usage Optimization Strategies
3.2.3 Tandem Multimeric Expression and Fusion Proteins
3.2.4 AMP Hybridization
4 Scale-Up from Small- to Large-Scale Fermentation
4.1 Batch Processes
4.2 Fed-Batch Processes
4.3 Continuous Processes
5 Purification of AMPs: Downstream Process Development
5.1 Recovery
5.2 Purification
6 Optimization of the Industrial Processes
7 Conclusions and Future Directions
References
Bioproduction of Cyclic Disulfide-Rich Peptides for Drug Modalities
1 Introduction
2 Potential High-Value Applications of CDRPs
3 Production of CDRPs
3.1 Synthetic Peptide Synthesis
3.2 Recombinant Bioproduction of CDRPs
3.2.1 Cyclization Strategies in Bioproduction of CDRPs
3.2.2 Recombinant Systems for Bioproduction of CDRPs
3.2.2.1 Intein-Mediated Microbial Bioproduction
3.2.2.2 AEP-Mediated Plant Bioproduction
3.2.2.3 AEP-Mediated P. pastoris-Based Bioproduction
4 Future Directions and Conclusions
References
Hyaluronic Acid (Hyaluronan)
1 Introduction
2 Biosynthesis Pathway
3 Rheological Properties
4 Fermentative Production
4.1 Natural Producers
4.2 Recombinant Production
4.3 In Vitro Production
5 Extraction and Purification
6 Commercial Producers
7 Patent
8 Conclusion and Future Outlook
References
Polyhydroxyalkanoates (PHA): Microbial Synthesis of Natural Polyesters
1 Introduction
2 PHA: General Aspects
2.1 Early Discovery of PHA
2.2 PHA Are Biosynthesized
2.2.1 ``Biopolymer´´ versus ``Bioplastic´´
2.3 PHA Play Multifaceted Roles in Nature
2.4 PHA Production Strains: Bacteria and Archaea as Cell Factories for Biopolymer Production
2.5 Renewable Resources as Feedstocks for PHA Production
3 P(3HB) Homopolyester
3.1 P(3HB)´s History
3.2 P(3HB) Properties
4 P(3HB-co-3HV) Copolyester, the Best Researched PHA Heteropolyester
4.1 The First Discovery of PHA Heteropolyesters
4.2 Biosynthesis of P(3HB-co-3HV)
4.3 Properties of P(3HB-co-3HV)
5 P(3HB-co-4HB) Copolyester
6 P(3HB-co-3HHx) Copolyester
7 Other PHA Copolyesters
8 Bioreactors, Cultivation Regimes, and Product Formation Conditions for PHA
8.1 Principle Aspects of PHA Cultivations
8.2 Continuous Cultivation
9 PHA Recovery
10 Commercialization of PHA
11 Spent PHA Is Naturally Degraded
11.1 P(3HB)
11.2 P(3HB-co-3HV)
11.3 P(3HB-co-4HB)
11.4 P(4HB)
11.5 P(3HB-co-3HHx)
12 Conclusions
References
Recent Advances in Poly-(γ-Glutamic Acid) Production by Microbial Fermentation
1 Research Progress of Poly-(γ-Glutamic Acid)-Producing Strains
1.1 Screening and Classification of Poly-(γ-Glutamic Acid)-Producing Strains
1.2 Mutagenic Breeding of γ-PGA-Producing Strains
1.3 Construction and Metabolic Regulation of Efficient Engineered γ-PGA Strains
1.3.1 Research Progress on Engineering of Wild-Strain γ-PGA-Producing Strains
1.3.2 Application of Synthetic Biology Techniques in γ-PGA-Producing Strains
2 Occurrence and Biosynthetic Mechanism of γ-PGA
2.1 Synthesis of γ-PGA Precursors
2.1.1 Synthesis of l-Glutamate
2.1.2 Synthesis of d-Glutamate
2.2 Polymerization of γ-PGA Precursors
3 Fermentation Engineering for γ-PGA Production
3.1 Fermentation Medium for Producing γ-PGA
3.1.1 The Effect of Carbon Source on γ-PGA Production
3.1.2 The Effect of Nitrogen Source on γ-PGA Production
3.1.3 The Effect of Metal Ions on the Yield of γ-PGA
3.2 Fermentation Factors for Producing γ-PGA
3.3 Fermentation Method for Producing γ-PGA
4 Separation and Purification of γ-PGA
5 Applications of γ-Polyglutamic Acid
5.1 Agricultural Planting
5.2 Food
5.2.1 Food Additives
5.2.2 Antifreeze Agents
5.2.3 Food Nutritions
5.3 Daily Chemical Products
5.3.1 Antioxidant
5.3.2 Skin Protection
5.4 Tissue Engineering, Regenerative Medicine, and Drug Delivery
5.4.1 Tissue Engineering and Regenerative Medicine Materials
5.4.2 Drug Carrier
5.5 Environmental Protection
6 Conclusion and Future Outlook
References
Bioengineering and Bioprocessing of Virus-Like Particle Vaccines in Escherichia coli
1 Introduction
2 VLPs and Immunogenicity
3 Bioengineering Strategies for Surface Presentation
3.1 Genetic Fusion
3.1.1 Genetic Fusion to Surface-Exposed Loops
3.1.2 Genetic Fusion to the N-Terminus or C-Terminus
3.2 Chemical Conjugation
3.3 Biochemical Conjugation
3.4 Capsid Protein Stoichiometry
3.5 Encapsulation
4 Bioengineering Strategies for Bioprocess Optimization
4.1 Upstream Bioprocess Optimization
4.2 Downstream Bioprocess Optimization by High-Throughput Screening
4.3 Platform Development to Reduce Production Cost
5 Conclusions and Perspective
References
Functional Inclusion Bodies
1 Introduction
2 Protein Production and IB Formation
3 Structure, Composition, and Activity of IBs
4 Stability of IBs
5 Inclusion Bodies as Active Nanoparticles: Applications
5.1 IBs in Biocatalysis
5.2 IBs in Therapy/Nanopills
5.3 IBs in Cancer
5.4 Antimicrobial IBs
5.5 IBs a Source of Soluble Protein
6 Conclusions
References
Encapsulin Nanocompartments for Biomanufacturing Applications
1 Introduction to Encapsulins
1.1 Encapsulin Structure
1.2 Encapsulin Function
1.3 Encapsulin Genetics and Evolution
2 Engineering Basics for Encapsulins
2.1 Methods for In Vivo Encapsulation
2.2 Methods for In Vitro Encapsulation
3 Examples of Biomanufacturing Using Encapsulins
3.1 Examples of In Vitro Nanoreactors
3.2 In Vivo Applications of Nanoreactors
4 Advanced Engineering and Examples in Biomanufacturing
4.1 Molecular Display on the Encapsulin Surface
4.2 Engineering Encapsulin Pores
4.3 Immobilisation of Encapsulin onto a Surface
4.4 Controlled Disassembly and Reassembly Using GALA Peptide
4.5 Engineering Targeting Peptide Interactions
4.6 Other Advanced Engineering Examples
5 Conclusions and Future Opportunities
References
Lumazine Synthase Nanocompartments
1 Introduction
2 Production of Lumazine Synthase Orthologs
3 Production of Aquifex aeolicus Lumazine Synthase
4 Production of AaLS-Based Nanocompartments
5 Conclusions and Prospects
References