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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5864_Библиотеки_им_академика_М_И_Перельмана.pdf
Introduction to Pharmaceutical Biotechnology, Volume 2 (Second Edition)
3 Industrial enzymes and their applications 3-1
3.1 Industrial enzymes 3-1
3.2 Bacterial α-amylases 3-1
3.3 Fungal α-amylases 3-7
3.4 Bacterial proteases 3-8
3.5 Fungal proteases 3-9
3.6 Glucose isomerase (d-xylose ketol-isomerase; EC. 5.3.1.5) 3-9
3.7 Penicillinase 3-11
3.8 Chloramphenicol acetyltransferase 3-13
3.9 Aminoglycoside antibiotic inactivating enzymes 3-13
3.10 Fibrinolytic enzymes 3-14
3.10.1 Streptokinase 3-15
3.10.2 Urokinase 3-17
3.10.3 Tissue plasminogen activator (t-PA) 3-17
3.11 Biotechnological applications of enzymes 3-18
3.11.1 Algae and plant research 3-18
3.11.2 Immobilization 3-18
3.12 Industrial enzymes 3-19
3.12.1 Glucoamylase 3-19
3.12.2 Cellulases 3-24
3.13 The role of enzymes in the synthesis of functional foods 3-28
3.13.1 Lipases 3-29
3.13.2 Proteases 3-30
3.13.3 Carbohydrate-modifying enzyme 3-31
3.13.4 Tannase 3-32
3.13.5 Asparaginase 3-32
3.13.6 The phytases 3-33
3.14 Enzymes used as additives to food 3-33
3.14.1 The enzymatic synthesis of dietary antioxidants 3-33
3.14.2 The use of ascorbyl esters 3-34
3.14.3 Polyphenolic esters 3-34
3.14.4 Synthesis of sugars esters surfactants by enzymes 3-35
References 3-36
4 Immobilization of enzymes 4-1
4.1 Introduction 4-1
4.2 Types of immobilization 4-3
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Introduction to Pharmaceutical Biotechnology, Volume 2 (Second Edition)
4.2.1 Surface immobilization by covalent coupling 4-3
4.2.2 Adsorption 4-6
4.2.3 Complexation and chelation 4-6
4.2.4 Within-support immobilization 4-7
4.2.5 Cell immobilization 4-8
4.2.6 Commercial production of enzymes 4-10
4.3 Genetic engineering for microbial enzyme production 4-10
4.3.1 Cloning methods 4-11
4.4 Protein studies for modification of commercial enzymes 4-12
4.5 Enzyme and cell immobilization 4-13
4.6 Immobilization methods 4-14
4.6.1 Adsorption methods 4-14
4.6.2 Nonspecific adsorption 4-14
4.6.3 Ionic binding 4-15
4.6.4 Hydrophobic adsorption 4-15
4.6.5 Affinity binding 4-15
4.6.6 Entrapment method 4-15
4.6.7 Covalent binding 4-17
4.6.8 Cross-linking 4-19
4.7 Choice of immobilization technique 4-20
4.7.1 Immobilization of l-amino acid acylase 4-20
4.7.2 Stabilization of soluble enzymes 4-20
4.8 Immobilization of cells 4-21
4.8.1 Immobilization of viable cells 4-22
4.8.2 Immobilized non-viable cells 4-22
4.8.3 Drawbacks of immobilizing eukaryotic cells 4-23
4.8.4 The effect of immobilization on enzyme properties 4-23
4.8.5 Immobilized enzyme reactors 4-23
4.8.6 Applications of immobilized enzymes and cells 4-25
4.9 Manufacture of commercial products 4-25
4.9.1 Production of l-amino acids 4-26
4.9.2 Production of high-fructose syrup 4-26
4.9.3 Immobilized enzyme and cell analytical applications 4-27
4.10 Immobilized enzymes for biomedical applications 4-28
4.11 Detecting biomass with immobilized cells via bioluminescence
4-31
and other biosensor uses
4.11.1 Bioluminescence 4-31
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4.11.2 The measurement of biomass using bioluminescence-based
4-32
techniques
4.11.3 Bioluminescence analysis for biomass captured in a
4-33
microfluidic device
4.11.4 Biosensors relying on bioluminescence 4-33
4.12 Bioluminescence-based microbial biosensors 4-34
4.12.1 The microencapsulation process involves the utilization
4-35
of polymers and cells
4.12.2 Microcapsule evaluation 4-36
4.12.3 Potential health benefits 4-38
4.12.4 Modern developments in cell encapsulation 4-38
4.13 Immobilization of microalgae 4-39
4.13.1 Techniques for immobilization 4-40
4.13.2 Use of cryopreserved algae 4-41
4.13.3 Removal of nitrogen and phosphorous 4-42
4.13.4 Disposal of metals 4-44
4.13.5 Biosensor development 4-46
References 4-47
5 Biosensors 5-1
5.1 Introduction 5-1
5.2 Principles of a biosensor 5-2
5.3 Different types of biosensors 5-3
5.3.1 Electrochemical biosensors 5-4
5.3.2 Thermometric biosensors 5-9
5.3.3 Optical biosensors 5-10
5.3.4 Piezoelectric biosensors 5-13
5.3.5 Whole-cell biosensors 5-14
5.3.6 Immunobiosensors 5-14
5.4 Applications of biosensors 5-15
5.4.1 Applications in medicine and health 5-16
5.4.2 Applications in industry 5-16
5.4.3 Applications in pollution control 5-16
5.4.4 Applications in the military 5-16
5.4.5 Immobilized enzymes and cell therapeutic applications 5-16
5.5 Recent advancements in biosensor technology 5-17
5.5.1 Electrochemical biosensors 5-18
5.5.2 Optical/visual biosensors 5-21
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Introduction to Pharmaceutical Biotechnology, Volume 2 (Second Edition)
5.5.3 Silica, quartz/crystal, and glass biosensors 5-22
5.5.4 Nanomaterials-based biosensors 5-23
5.5.5 Fluorescent biosensors that are either genetically encoded or
5-23
synthetic
5.6 Microbial biosensors utilizing synthetic biology and genetic/protein
5-24
engineering techniques
5.7 Technological comparison of biosensors 5-25
5.8 Prospective challenges, and inherent limitations associated with
5-29
biosensor technology
5.9 Grand challenges in biosensors and biomolecular electronics 5-30
5.9.1 Sensitivity 5-31
5.9.2 Multiplex capability 5-32
5.9.3 Continuous monitoring in vivo 5-32
5.10 The Implementation and commercialization of biosensing devices 5-33
5.10.1 Sustainability to the ecosystem 5-34
References 5-35
6 Biotransformation and enzymes 6-1
6.1 Introduction 6-1
6.2 Types of biotransformation reactions 6-1
6.3 Sources of biocatalysts and techniques for biotransformation 6-2
6.3.1 Growing cells 6-3
6.3.2 Non-growing cells 6-3
6.3.3 Immobilized cells 6-3
6.3.4 Immobilized enzymes 6-3
6.4 Product recovery in biotransformations 6-4
6.5 Application of biotransformation in the production of
pharmaceutical products
6.5.1 Biotransformation of steroids 6-4
6.5.2 Biotransformation of antibiotics 6-6
6.5.3 Biotransformation of arachidonic acid to prostaglandins 6-10
6.5.4 Biotransformation for the production of ascorbic acid 6-10
6.5.5 Biotransformation of glycerol to dihydroxyacetone 6-10
6.5.6 Biotransformation for the production of indigo 6-11
6.6 Mechanisms of enzyme action in biotransformation 6-11
6.6.1 Enzyme kinetics and biotransformation 6-11
6.6.2 Cofactors and coenzymes in biotransformation 6-12
6.6.3 Enzyme inhibition and activation 6-12
6-4
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6.6.4 Role of enzyme specificity and selectivity 6-13
6.7 Biotransformation in environmental applications 6-13
6.7.1 Degradation of pollutants 6-14
6.7.2 Enzymatic breakdown of pesticides 6-15
6.8 Emerging technologies in biotransformation 6-16
6.8.1 Enzyme engineering and directed evolution 6-16
6.8.2 Production of flavors and fragrances 6-17
6.8.3 Biotransformation of lipids for healthy oils 6-17
6.8.4 Fermentation and enzymatic modification of food products 6-18
6.9 Biotransformation challenges and future perspectives 6-18
6.9.1 Scalability issues in industrial applications 6-18
6.9.2 Regulatory and safety concerns 6-19
6.9.3 Challenges in enzyme storage and stability 6-19
6.9.4 Future trends and emerging areas of research 6-19
6.9.5 Biotransformation in biofuel production 6-20
6.9.6 Biotransformation in the cosmetic industry 6-20
6.9.7 Specialized enzyme systems: lignin-modifying enzymes in
6-20
biotransformation
References 6-21
7 Introduction to genomics 7-1
7.1 Introduction 7-1
7.2 Characterizations in genomics 7-2
7.3 Historical background 7-3
7.4 Genome sequencing 7-3
7.4.1 Clone-by-clone sequencing 7-4
7.4.2 Human whole-genome shotgun sequencing 7-5
7.4.3 Compilation of genome resources 7-7
7.5 Understanding bioinformatics and sequencing 7-9
7.6 Comparative genomics as a technique to understand evolution 7-12
7.6.1 The role of exon shuffling 7-12
7.6.2 Horizontal or lateral gene transfer 7-13
7.6.3 Genome similarity or homology 7-14
7.6.4 SNPs 7-15
7.6.5 Inferences from comparative genomics 7-17
7.6.6 Gene order comparisons (for phylogenetic inference) 7-21
7.6.7 Phylogenetic footprinting (computational method) 7-21
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Introduction to Pharmaceutical Biotechnology, Volume 2 (Second Edition)
7.6.8 Origins, evolution and phenotypic impact of new genes 7-22
7.6.9 The concept of minimum genome size 7-23
7.6.10 Comparative genomics analysis of mitochondria and
7-24
chloroplasts
7.7 Gene estimation and counting 7-26
7.7.1 Genome similarity, SNPs and comparative genomics 7-26
7.8 Genomes: genome evolution 7-27
7.8.1 Microbial genome reduction in bacteria 7-28
7.8.2 Role of duplications in the origin and evolution of the
7-29
eukaryotic genome
7.8.3 Gene duplications increase genetic diversity and complexity 7-31
7.9 Algae bioinformatics 7-32
7.9.1 Scope of algae bioinformatics 7-33
7.9.2 What is involved in algae bioinformatics 7-33
7.9.3 Role of algae bioinformatics 7-33
7.9.4 Steps involved in obtaining the data for analysis using
7-33
bioinformatics
7.10 Functional genomics 7-33
7.10.1 Introduction to functional genomics 7-34
7.10.2 Transcriptomics: studying the RNA molecules 7-34
7.10.3 Proteomics: understanding the world of proteins 7-34
7.10.4 Metabolomics: exploring cellular metabolites 7-34
7.10.5 Interactomics investigating protein–protein interactions 7-35
7.11 Structural genomics 7-35
7.11.1 Introduction to structural genomics 7-36
7.11.2 The approaches used in the domain of structural genomics 7-36
7.11.3 Importance of structural genomics in drug design 7-36
7.12 Epigenomics and epigenetics 7-37
7.12.1 Epigenetic inheritance and diseases 7-38
7.13 Pharmacogenomics 7-39
7.13.1 The importance of personalized medicine 7-39
7.13.2 The impact of genetic variations on drug response 7-40
7.13.3 Additional insights on pharmacogenomics 7-40
7.13.4 Pharmacogenomic tests in the market 7-41
7.13.5 Challenges in implementing pharmacogenomics 7-41
7.14 Population genomics 7-41
7.14.1 Studying genetic variation across populations 7-42
7.14.2 Population genomics techniques 7-42
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7.14.3 Understanding human migration and evolution through
7-42
population genomics
7.14.4 Conservation genomics in endangered species 7-43
7.15 Microbiome genomics 7-43
7.15.1 Introduction to the human microbiome 7-44
7.15.2 Techniques in studying microbial communities 7-44
7.15.3 Role of microbiome in human health and disease 7-44
7.15.4 Environmental microbiomes and their importance 7-45
7.16 Synthetic biology and genome editing 7-45
7.16.1 Techniques like CRISPR/Cas9 in genome editing 7-46
7.17 Systems biology and genomics 7-46
7.17.1 Integrative approaches in genomics 7-47
7.17.2 Modeling biological systems and networks 7-48
7.17.3 Challenges and opportunities in systems biology 7-48
7.18 Genome-wide association studies (GWAS) 7-48
7.18.1 Introduction to GWAS 7-48
7.18.2 Techniques and platforms for GWAS 7-49
7.18.3 Challenges in interpreting GWAS results 7-49
7.18.4 Case studies: notable findings from GWAS 7-49
7.19 Future of genomics 7-49
7.19.1 Next-generation sequencing technologies 7-50
7.19.2 Ethical considerations in genomics research 7-50
7.19.3 The role of AI and machine learning in genomics 7-51
7.19.4 Personalized medicine and its potential impact 7-51
References 7-51
8 Basics of proteomics 8-1
8.1 Introduction 8-1
8.2 Types of proteomics 8-2
8.2.1 Structural proteomics 8-2
8.2.2 Functional proteomics (strategy) 8-4
8.2.3 Expression proteomics 8-4
8.3 Basic techniques involved in proteomics 8-5
8.3.1 Sequence alignment (algorithms) 8-5
8.3.2 Protein structure (annotation resources) 8-6
8.3.3 Protein structural investigation 8-7
8.3.4 Two-dimensional gel electrophoresis in proteomics 8-7
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8.3.5 Domain fusion method (or rosetta stone method) 8-8
8.4 Complete proteome of Mycoplasma genitalium 8-9
8.5 Architecture and design of the nuclear pore complex 8-9
8.6 Functional genomics and systems biology 8-10
8.6.1 Gene expression profiling 8-12
8.6.2 Transcriptome, proteome and genomes 8-14
8.6.3 DNA arrays: a potential genomic tool 8-16
8.6.4 Gene function determination from sequence information 8-20
8.6.5 Protein interactions 8-22
8.7 Synthetic genomics 8-28
8.8 Advanced techniques in proteomics 8-30
8.8.1 Mass spectrometry in proteomics 8-30
8.8.2 Tandem mass spectrometry 8-31
8.8.3 Quantitative proteomics using mass spectrometry 8-31
8.8.4 Other advanced techniques in proteomics 8-32
8.8.5 Chromatography in proteomics 8-33
8.9 Proteogenomics 8-34
8.9.1 Proteogenomics role in precision medicine 8-35
8.9.2 Novel peptide identification in proteogenomics 8-35
8.10 Single-cell proteomics 8-36
8.10.1 Technologies enabling single-cell proteomics 8-37
8.11 Clinical and diagnostic proteomics 8-38
8.12 Metaproteomics 8-39
8.13 Emerging topics in proteomics 8-40
8.13.1 Data-independent acquisition (DIA) 8-40
8.13.2 Top-down proteomics 8-40
8.13.3 Targeted proteomics and selected reaction monitoring (SRM) 8-41
8.13.4 Proteomics in plant research 8-41
8.14 Ethical and data management issues in proteomics 8-41
8.14.1 Open-source platforms for proteomic analysis 8-43
8.15 Cellular and molecular dynamics 8-43
8.15.1 Molecular mechanisms of protein function 8-44
8.15.2 Protein degradation pathways 8-44
8.15.3 Post-translational modifications and protein function 8-45
8.15.4 Cellular signaling pathways 8-45
8.15.5 Proteomic analysis of signaling networks 8-46
8.15.6 Signaling pathway dysregulation in disease 8-46
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8.15.7 Targeting signaling pathways in drug discovery 8-46
8.15.8 Crosstalk between signaling pathways 8-47
8.16 Membrane proteomics 8-48
8.16.1 Techniques for membrane protein analysis 8-48
8.16.2 Membrane protein structure and function 8-48
8.16.3 Membrane proteins in disease 8-49
8.16.4 Drug targeting of membrane proteins 8-49
8.17 Subcellular proteomics 8-50
8.17.1 Organelle-specific proteomics 8-50
8.17.2 Protein localization and trafficking 8-50
8.17.3 Proteomics of cellular compartments 8-51
8.17.4 Techniques for subcellular proteomic analysis 8-51
References 8-52
9 Bioinformatics 9-1
9.1 Introduction 9-1
9.2 History of bioinformatics 9-2
9.3 Sequences and nomenclature 9-4
9.3.1 DNA sequences 9-5
9.3.2 Amino acid sequences of proteins 9-5
9.3.3 Types of sequences in nucleotide sequence databases 9-5
9.3.4 Databases 9-7
9.3.5 Search engines and analysis tools 9-9
9.3.6 Various indian databases 9-12
9.4 Investigation by means of bioinformatics tools 9-12
9.4.1 Identification of genes 9-13
9.4.2 Identification of the function of a new gene 9-14
9.4.3 Identification of functional domains 9-14
9.4.4 Detection of noncoding RNA 9-14
9.4.5 Genome annotation 9-15
9.4.6 Molecular phylogenetics 9-15
9.5 Computational approaches in bioinformatics 9-15
9.5.1 Algorithm development 9-15
9.5.2 Phylogenetic tree construction algorithms 9-16
9.5.3 Machine learning algorithms in bioinformatics 9-17
9.5.4 High-performance computing (HPC) in bioinformatics 9-19
9.5.5 Cloud computing in genomics 9-19
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9.5.6 GPGPU (general-purpose computing on graphics
9-20
processing units)
9.5.7 Big data analytics in bioinformatics 9-21
9.5.8 Systems biology modelling 9-21
9.5.9 Systems pharmacology 9-22
9.5.10 Multiscale modeling 9-22
9.5.11 Computational genomics 9-23
9.5.12 Functional genomics 9-23
9.5.13 Comparative genomics 9-24
9.5.14 Epigenomics 9-24
9.5.15 Metagenomics 9-24
9.6 Bioinformatics in precision medicine 9-25
9.7 Translational bioinformatics 9-26
9.8 Bioinformatics in drug discovery and development 9-27
9.8.1 Artificial intelligence (AI) and machine learning in
9-29
bioinformatics
9.8.2 AI-driven drug discovery 9-29
9.9 CRISPR and genome editing in bioinformatics 9-31
9.10 Integrative and multi-omics analysis 9-32
References 9-33
10 Protein and enzyme engineering 10-1
10.1 Protein and enzyme engineering 10-1
10.2 Designing macromolecules 10-1
10.3 Protein engineering versus enzyme engineering 10-4
10.4 Protein engineering 10-5
10.5 Foundation of protein (enzyme) engineering 10-6
10.6 Basic assumptions for protein engineering 10-7
10.7 Steps involved in protein engineering 10-8
10.7.1 Studying three-dimensional protein structure 10-8
10.7.2 Protein modeling 10-9
10.7.3 Perturbation theory 10-10
10.8 Methods of protein engineering 10-10
10.9 Mutagenesis and selection of mutant enzymes 10-10
10.10 Gene modifications or gene synthesis for protein engineering 10-11
10.11 Multi-enzyme systems 10-12
10.12 Chemical modification of enzyme 10-13
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