Biomanufacturing for sustainable production of biomolecules: 2023

This book elucidates the sustainable production of commercially important biomolecules in medicines, food, and beverage processing, through biological systems, including microorganisms, animal cells, plant cells, tissues, enzymes, and in vitro. It discusses promising technologies for the manipulation of cells including, genetic engineering, synthetic biology, genome editing, and metabolic engineering. The initial chapters of the book introduce topics on biomanufacturing, circular economy, strain design and improvement, upstream and downstream processing. The subsequent chapters cover artificial intelligence-assisted production, designer cell factories, biosensors for monitoring biomolecules, different cells factories, biosynthetic pathways, and genome editing approaches for scale-up biomanufacturing. Lastly, the book discusses the opportunities and challenges of implementing biological systems for the production of biomolecules. ​This book is a valuable source for students, researchers, scientists, clinicians, stakeholders, policymakers, and practitioners to understand biomanufacturing for the sustainable production of biomolecules. Foreword Preface Acknowledgment Contents Editors and Contributors 1: Strain Design and Optimization Methods for Sustainable Production 1.1 Introduction 1.2 Strain Design and Development 1.2.1 Concept 1.2.2 Methods and Tools 1.2.2.1 Chassis Selection 1.2.2.2 Pathway Implementation 1.2.3 Rewiring the Cell and Production Optimization 1.3 Success Stories 1.3.1 E. coli Cell Factories on the Horizon 1.3.2 An Explorative Journey into Yeast Platform Strains 1.3.3 Fungi as Cell Factories 1.3.4 Towards Mammalian Cell Factories 1.4 Perspectives References 2: Minimal Cells and Genome Minimization: Top-Down and Bottom-Up Approaches to Construct Synthetic Cells 2.1 Genome Minimization 2.1.1 Construction of a Minimal Genome 2.1.1.1 Top-Down Approach for Genome Minimization 2.1.1.2 Bottom-Up Approach for Genome Minimization 2.1.2 Essential and Non-essential Genes 2.1.2.1 Essential Genes 2.1.2.1.1 Transposon Mutagenesis 2.1.2.1.2 Antisense RNA 2.1.2.1.3 Systematic Inactivation of Genes 2.1.2.2 Non-essential Genes 2.1.3 Minimal Genomes 2.1.3.1 Bacterial Genome Minimization 2.1.3.1.1 E. coli 2.1.3.1.2 Mycoplasma 2.1.3.1.3 B. subtilis 2.1.3.2 Yeast 2.1.4 Naturally Occurring Minimal Genomes 2.1.5 Applications of Minimal Genomes 2.1.6 Limitations of Genome Minimization 2.2 Synthetic Minimal Cells 2.2.1 Membrane 2.2.1.1 GUVs 2.2.1.2 Proteinosomes 2.2.1.3 Polymersomes 2.2.2 RNA Cell 2.2.3 Cell-Matrix-Cell Dynamics 2.2.4 Synthetic Cell Communication 2.2.5 Energy Currency 2.3 Conclusion References 3: Recent Advances in Downstream Processing Deployed in the Treatment of Pharmaceutical Effluents 3.1 Introduction 3.2 Pharmaceutical Wastewater 3.2.1 The Sources of Pharmaceutical Waste 3.2.2 Requirement of Effluent Treatment Linked with Pharmaceutical Waste 3.2.3 Treatment of Wastewater 3.3 Current Approaches in Downstream Processing Related to Treatments of Pharmaceutical Wastewater 3.3.1 Coagulation and Sedimentation 3.3.2 Flotation 3.3.3 Absorption of Activated Charcoal 3.4 Emerging Treatment Processes 3.4.1 Advanced Oxidation Processes 3.4.1.1 Application of AOPS 3.4.2 Wet Air Oxidation (WAO) 3.4.2.1 Wet-Air Oxidation Industrial Applications 3.4.3 Supercritical Water Oxidation (SCWO) 3.4.3.1 Application of Supercritical Water Oxidation 3.4.4 Photocatalysis 3.4.4.1 Advantages of Photocatalysis 3.5 Conclusion References 4: Microbial Conversion of Waste to Biomolecules 4.1 Introduction 4.1.1 Waste for Biomolecule Production 4.1.1.1 Food Waste 4.1.1.2 Lignocellulosic Biomass 4.1.1.3 Municipal Solid Waste 4.2 Microbial Conversion of Waste by Microorganism 4.2.1 Introduction to Microbial Conversion 4.2.2 Biowaste to Biomolecules 4.2.2.1 Biowaste Conversion to Biomolecules from Plant Origin 4.2.2.1.1 Polysaccharides 4.2.2.1.2 Lactic Acids 4.2.2.1.3 Pectins 4.2.2.2 Biowaste Conversion to Biomolecules from Animal Origin 4.2.2.2.1 Hydroxyapatite 4.2.2.2.2 Collagen 4.2.2.2.3 Biohydrogen 4.3 Potential and Challenges of Microbial Conversion of Waste 4.3.1 Potential Solution to Environmental Concern on Waste Management 4.3.2 Waste as Feedstock for Bioeconomy 4.3.3 Sustainable Production of Value-Added Product 4.3.4 Challenges to Microbial Conversion of Waste 4.4 Conclusion References 5: Biosensor for Detecting Biomolecules 5.1 Introduction 5.2 Concept 5.2.1 Principles of Optical Biosensors 5.2.2 Principles of Electrochemical Biosensors 5.2.3 Principles of Thermal Biosensors 5.2.4 Principles of Piezoelectric Biosensors 5.3 Biosensor Design: Materials, Fabrication, and Modification 5.3.1 Acetylcholinesterase Inhibition-Based Biosensors 5.3.2 Microalgae Biosensors 5.3.3 Yeast-Based Biosensors 5.3.4 Nanomaterial-Based Biosensors 5.3.5 Microbial Fuel Cell-Based Biosensors 5.4 Recent Advances in Biosensor Technology 5.4.1 Functionalization of Sensing Material 5.4.2 Configuration of Porous Detection Platform to Ease the Sensing Activities 5.4.3 Development of Biosensor for COVID-19 Detection 5.5 Conclusions, Future Prospects, and Challenges References 6: Artificial Intelligence-Assisted Production of Biomolecules 6.1 Introduction 6.2 Machine Learning in Production of Biomolecules 6.3 Deep Learning in the Production of Biomolecules 6.4 Polymeric Biomaterial Applications Using Machine Learning 6.5 Self-Assembled Dipeptide Hydrogels Using Machine Learning 6.6 Response of Cell and Adsorption of Proteins on Polymeric Surfaces Using Machine Learning 6.7 Prediction of Protein Structure Using Deep Learning 6.8 Emerging Trends in ML-Based Enzyme Engineering Approaches 6.9 Artificial Intelligence-Assisted Ultrasonic Extraction of Flavonoids 6.10 Biological Data Interpretation and Integration with Other Omic 6.11 NMR Databases and Software for Metabolite Identification 6.12 Automated Structural Classification of Lipids Using Machine Learning 6.13 AI Research on the Production of Nutrient Biomolecules 6.14 Summary References 7: Escherichiacoli Cell Factory for Synthesis of Biomolecules 7.1 Introduction 7.2 Metabolic Engineering of Escherichia coli 7.2.1 Central Metabolism 7.2.2 Production of Ethanol 7.2.3 Production of Acetate 7.2.4 Production of Lactate 7.2.5 Production of Succinate 7.3 Optimisation for the Production of Bioactive Compounds 7.3.1 Precursor Pools 7.3.2 Cofactor Levels 7.3.3 Gene Expression Balancing Levels 7.3.4 Substrate Channelling 7.3.5 Pathway Modularisation 7.4 Bioactive Compounds from E. coli 7.4.1 Organic Acids 7.4.2 Biodiesels 7.4.3 Polyhydroxyalkanoates 7.4.4 Hydrogen 7.4.5 Flavour and Fragrance 7.5 Future, Advances and Applications 7.6 Conclusion References 8: Bacillus subtilis Cell Factory 8.1 Introduction 8.2 Bacillus subtilis Cell Factory for Vitamin Production 8.3 Bacillus subtilis Cell Factory in the Production of Industrially Important Enzymes 8.3.1 Amylase 8.3.2 Xylanases 8.3.3 Lichenase 8.4 Role of Bacillus subtilis in Terpenoid Biosynthesis 8.5 Genetic Engineering Tools and Strategies to Improve B. subtilis Cell Factory 8.6 Potential Application of Bacillus subtilis in Agriculture References 9: Biomanufacturing for Sustainable Production of Biomolecules: Pseudomonas putida Cell Factory 9.1 Introduction 9.2 Cell Factory Engineering and Tolerance 9.2.1 Cell Genetic Tolerance 9.2.2 Optimal Flux Engineering 9.2.3 Biosurfactant Synthesis 9.2.4 Biofilm Cultivation 9.3 Metabolic Engineering Production 9.3.1 Rhamnolipids 9.3.2 Ethylene Glycol 9.3.3 Terpenoids 9.3.4 Polyketides and Non-ribosomal Peptides 9.4 Industrial Application 9.5 Conclusion References 10: Cyanobacteria for Marine-Based Biomolecules 10.1 Introduction 10.2 An Outlook of Cyanobacteria Metabolites 10.3 Potentials of Cyanobacteria 10.3.1 Cyanobacteria Potential: Biofuel 10.3.2 Cyanobacteria Potential: Parasitic Nematodes Management 10.3.3 Cyanobacteria Potential: Nutraceutical 10.3.4 Cyanobacteria Potential: Biofertilizer 10.4 Biomolecules Diversity and Genetic Engineering of Cyanobacteria 10.4.1 Pigments 10.4.2 Carbohydrates 10.4.3 Protein 10.5 Medicinal and Clinical Applications 10.6 Sustainable Production of Cyanobacteria-Based Biomolecules 10.7 Overall Challenges in the Development of Cyanobacteria 10.8 Future Perspective 10.9 Summary References 11: Yeast Cell Factory for Production ofBiomolecules 11.1 Introduction 11.1.1 Why Yeast Is Used as Cell Factory? 11.1.1.1 Methylotrophic Yeast 11.1.1.2 Non-methylotrophic Yeast 11.1.1.2.1 Saccharomyces cerevisiae 11.1.1.2.2 Pichia pastoris 11.1.1.2.3 Hansenula polymorpha 11.1.1.2.4 Yarrowia lipolytica 11.1.1.2.5 Kluyveromyces lactis 11.1.1.2.6 Schizosaccharomyces pombe 11.2 Tools and Strategies 11.2.1 Promoters as Tool 11.2.1.1 Structure of Yeast Promoters 11.2.1.1.1 Core Promoter Region 11.2.1.1.2 UAS and URS 11.2.1.1.3 Nucleosomes Disfavoring Sequences 11.2.1.2 Types of Promoters 11.2.1.3 Promoter Engineering 11.2.2 Native Promoters 11.2.3 Hybrid Promoters 11.2.4 Synthetic Promoters 11.2.4.1 Synthetic Promoters Controlled by Bacterial Proteins 11.2.4.1.1 Promoters Regulated by LexA 11.2.4.1.2 Promoters Regulated by TetR 11.2.4.1.3 Promoters Regulated by LacI 11.2.4.1.4 Promoters Regulated by XylR 11.2.4.2 Synthetic Promoters for Expanding Dynamic Ranges 11.2.4.3 Synthetic Promoters for Reducing Homologous Recombination 11.2.4.4 Synthetic Promoters with Minimal Size 11.2.4.5 Synthetic Promoters for Multi-host Application 11.2.4.6 Applications of Yeast Cell Factories 11.2.4.7 Biofuel Synthesis 11.2.4.8 Production of Virus-Like Particles (VLP) 11.2.4.9 Biomass Utilization 11.2.4.10 Synthesis of Fatty Acids and Derived Products 11.2.4.11 Pharmaceutical Protein Production 11.2.4.12 Genome Editing 11.2.4.13 Miscellaneous Applications 11.2.4.13.1 Yarrowia lipolytica as Cell Factory 11.2.4.13.2 Production of Lipids 11.2.4.13.3 Pichia pastoris as Cell Factory 11.2.4.13.4 Heterologous Protein Production 11.2.4.13.5 Production of Industrial Enzymes 11.2.4.13.6 Schizosaccharomyces pombe as Cell Factory 11.2.4.13.7 Kluyveromyces lactis as Cell Factory 11.3 Concluding Remarks References 12: Plant Cell Factory for Production ofBiomolecules 12.1 Introduction 12.2 Production of Iron-Containing Biomolecules 12.2.1 Role of Transcription Factors in Equanimity of Iron 12.2.2 Classical and Traditional Avenue for Biofortifying Iron 12.2.3 How Hindrance of Iron Affects Plastids 12.2.4 Iron Deficiency-Induced Genes 12.3 In Vitro Culture of Varied Plant Species in the Production of Caffeoylquinic Acids CQAs and Their By-Products 12.3.1 Involvement of Shikimic Pathway in Synthesizing CQAs 12.3.2 CQAs Compound Isolation from Epiphytes 12.3.3 Quantitative and Qualitative Approaches for Identification 12.4 Biosynthesis of Zinc/ZnO-Containing Nanoparticles in Plants 12.4.1 Enhancing Attributes of Maize Plant Using ZnO Nanoparticles 12.4.2 Distinct Approaches for Forming Zinc NP Using Plant Extracts 12.4.3 Zn Nanoparticle in Regard to Toxicity 12.4.4 Effect of Zn NP on Mutagenicity of Barley References 13: Genetic Manipulation of Crop for Enhanced Food Quality and Nutrition Toward Sustainable Production 13.1 Introduction 13.2 Improving Food Quality and Nutrition Through Plant Breeding 13.3 Chromosome and Embryo Manipulation 13.4 Transgenic Technologies 13.5 Potential of Genome Editing in Crop Improvement 13.6 Synthetic Biology for Future Agriculture and Nutrition 13.7 Application of Plant Biotechnology in Nutritional Therapy, Phytonutrients, and Phytotherapy 13.8 Conclusions and Future Remarks References 14: Insect Cell Factory for Production of Biomolecules 14.1 Introduction 14.2 Insect Cells 14.3 Insect Cell Metabolism 14.4 By-products of Insect Cells 14.5 Vector for Insect Cell Infection 14.6 Cultivation of Insect Cells 14.7 Insect Cell-Baculovirus System Proteolysis 14.8 Screening Transformed Insect Cell Lines for Recombinant Protein Production 14.9 Potential for O-Glycosylation in Lepidopteran Insect Cell Lines 14.10 Post-translational Events and Protein Folding 14.11 Expression of Human Sialic Acid Pathway Gene in Insect Cells (Spodoptera frugiperda) 14.12 Enhanced Secreted and Membrane-Targeted Protein Expression in Insect Cells References 15: Mammalian Cell Culture: An Edge to Biopharmaceutical Industry 15.1 Introduction 15.1.1 Current Situation of Mammalian Cell Culture Market 15.2 Market Size 15.3 Geographic Distribution of Cell Culture Capacity 15.4 Equipment Required for Mammalian Cell Culture 15.4.1 Cell Culture Process 15.4.1.1 Seed Train Expansion or Inoculum Train 15.4.1.2 Production Bioreactor 15.4.2 Bioreactor Types 15.4.2.1 Homogeneous System 15.4.2.1.1 Stirred Tank Bioreactor 15.4.2.1.2 Bubble Tank Bioreactor 15.4.2.1.3 Airlift Bioreactor 15.4.2.1.4 WAVE Bioreactor 15.4.2.1.5 Rocking Bioreactor 15.4.2.2 Heterogeneous System 15.4.2.2.1 Stirred Tank Bioreactor with Microcarriers 15.4.2.2.2 Fixed-Bed Bioreactor 15.4.2.2.3 Fluidized-Bed Bioreactor 15.4.2.2.4 Immobilized-Bed Bioreactor 15.4.2.2.5 Hollow-Fiber Bioreactor 15.4.3 Bioreactor Operation Modes 15.4.3.1 Batch Culture 15.4.3.2 Fed-Batch Culture 15.4.3.3 Continuous Culture 15.4.3.4 Repeated Fed-Batch/ Semicontinuous Culture 15.5 Approaches for Protein Expression 15.5.1 Internal Ribosome Entry Site (IRES) 15.5.2 Ubiquitous Chromatin Opening Element (UCOE) 15.5.3 Selection Marker Attenuation 15.5.4 Matrix Attachment Regions 15.5.5 Site-Specific Recombination 15.6 Conclusion References 16: Genome Editing in the Synthetic Biology for Sustainable Production of Biomolecules 16.1 Introduction 16.2 Synthetic Biology Tools for Biomolecules Production 16.2.1 Conventional Genetic Engineering Techniques for Biomolecule Production 16.2.2 Genome Editing Based on CRISPR/Cas9 System 16.2.3 Mechanism of CRISPR/Cas9 16.3 Potential Advantages 16.3.1 Role in Gene Therapy 16.3.2 Therapeutic Role of CRISPR/Cas9 16.4 Disadvantages or Drawbacks of CRIPSR 16.4.1 Lack of Equipment 16.4.2 Lack of Assured Efficiency 16.4.3 Due to Off-Target Pairing 16.5 Genome Editing for the Production of High-Value Biomolecules 16.5.1 Genome Editing for Production of High-Value Biomolecules in Bacteria 16.5.2 Genome Editing for High-Value Production of Biomolecules in Yeast 16.5.3 Genome Editing for Production of High Value Biomolecules in Fungi 16.6 Summary References 17: Cell-Free Systems for Sustainable Production of Biofuels 17.1 Introduction 17.2 Cell-Free System for Production of Ethanol 17.3 Cell-free System for Butanol Production 17.4 Cell-free System for Hydrogen Production 17.5 Production of Advanced Biofuels 17.5.1 Isoprene 17.5.2 Bisabolene 17.5.3 Limonene 17.5.4 Pinene 17.5.5 Sabinene 17.5.6 Farnesene 17.6 Conclusion and Future Remarks References 18: Challenges and Opportunities in Biomanufacturing 18.1 Introduction 18.2 Biomanufacturing Revolutions 18.2.1 Premodern Biomanufacturing 18.2.2 Biomanufacturing 1.0 18.2.3 Biomanufacturing 2.0 18.2.4 Biomanufacturing 3.0 18.2.5 Emerging Biomanufacturing 4.0 18.3 Challenges and Opportunities in Biomanufacturing 18.3.1 Food and Beverage Biomanufacturing 18.3.2 Biomanufacturing in Tissue Engineering and Regenerative Medicine 18.3.3 Biomanufaturing of Medicines and Pharmaceuticals 18.3.4 Biomanufacturing of Therapeutic Cells 18.4 Concluding Remarks and Future Directions References