Pharmaceutical Biocatalysis: Drugs, Genetic Diseases, and Epigenetics

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Chapter 1: Fermentative Production of Vitamin B6
	1.1: Introduction
	1.2: De novo Synthesis of Vitamin B6
	1.3: Control of Vitamin B6 Homeostasis
	1.4: Engineering Microorganisms for the Production of B6 Vitamers
	1.5: Novel Routes for Vitamin B6 Biosynthesis and Production
	1.6: Rational Design and Construction of a Vitamin B6-Producing Bacterium
	1.7: Alternative Approaches for Enhancing Vitamin B6 Production
	1.8: Conclusions
Chapter 2: Exploring Alternative Taxol Sources: Biocatalysis of 7-β-Xylosyl-10-Deacetyltaxol and Application for Taxol Production
	2.1: Introduction
	2.2: High-Cell-Density Fermentation of the Engineered Yeast
		2.2.1: General Fed-Batch HCDF Process
		2.2.2: HCDF Process Optimization
			2.2.2.1: Elimination of pure oxygen supplement by increasing air pressure
			2.2.2.2: Fermentation using biomass-stat strategy
			2.2.2.3: Fermentation using reduced induction DO value
			2.2.2.4: Optimization of initial induction biomass
		2.2.3: Scaling Up HCDF from Pilot Scale to Demonstration/Commercial Scale
	2.3: Biocatalysis of 7-β-Xylosyltaxanes
		2.3.1: General Biocatalysis Protocol
		2.3.2: Optimization of the Biocatalysis
			2.3.2.1: Impact of dry cell amount on biocatalysis
			2.3.2.2: Impact of DMSO concentration on biocatalysis
			2.3.2.3: Impact of substrate concentration on product yield
			2.3.2.4: Effect of antifoam supplement on biocatalysis
		2.3.3: Scale-Up Biocatalysis
	2.4: One-Pot Enzymatic Reaction from 7-β-Xylosyl-10-Deacetyltaxol to Taxol
		2.4.1: Reaction System for the Biocatalysis
		2.4.2: Protein Engineering of the 10-β-Acetyltransferase
			2.4.2.1: L-Alanine scanning mutagenesis
			2.4.2.2 Saturation mutagenesis
			2.4.2.3 Construction of one-pot reaction system
	2.5 Summary
Chapter 3: Molecular Farming through Plant Engineering: A Cost-Effective Approach for Producing Therapeutic and Prophylactic Proteins
	3.1: Introduction
	3.2: Strategies for Production of Therapeutics in Plants
		3.2.1: Stable Expression
		3.2.2: Transient Expression
	3.3: Plant-Made Vaccines
	3.4: Plantibodies
	3.5: Conclusions
Chapter 4: Microbial Biotransformations in the Production and Degradation of Fluorinated Pharmaceuticals
	4.1: Introduction
	4.2: Fluorinated Natural Products
	4.3: Production of Fluorinated Antibiotics in Microorganisms
	4.4: Biological Production of [18F]-Labelled Compounds for PET Analysis
	4.5: Microorganisms that Enable Fluorinated Drug Design
	4.6: Production of Fluorinated Drug Metabolites in Microorganisms
	4.7: Microbial Degradation of Fluorinated Drugs
	4.8: Future Prospects and Challenges
Chapter 5: Successful Screening of Potent Microorganisms Producing L-Asparaginase
	5.1: Introduction
	5.2: Purpose of Screening Prospective Source of L-Asparaginase
		5.2.1: High Cost of Treatment
		5.2.2: Minimizing Side Effects
		5.2.3: Prolongation of Half-Life
		5.2.4: Explore the Multifaceted Use of L-Asparaginase
	5.3: Different Methods of Screening Potential Sourceof L-Asparaginase
		5.3.1: In silico Approach
		5.3.2: Dye-Based Method
		5.3.3: Assay-Based Method
			5.3.3.1: Radioactive isotope assays
			5.3.3.2: Indophenol assay
			5.3.3.3: Coupled assay
			5.3.3.4: Aspartic acid determination assay
			5.3.3.5: Hydroxylamine assay
			5.3.3.6: Fluorometric assay
			5.3.3.7: Direct nesslerization assay
	5.4: Activators and Inhibitors of L-Asparaginase
	5.5: Various Microbial Sources of L-Asparaginase
		5.5.1: Microbial Sources
			5.5.1.1: Bacterial source
			5.5.1.2: Fungal source
		5.5.2: Plant Source
		5.5.3: Animal and Other Sources
	5.6: Pharmaceutical Application of L-Asparaginase
		5.6.1: Chemotherapy
		5.6.2: Infectious Disease
		5.6.3: Autoimmune Disorder
		5.6.4: Veterinary
		5.6.5: Food Additive
		5.6.6: Medical/Food Biosensor
	5.7: Conclusion
Chapter 6: Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
	6.1: Introduction
	6.2: Liver Metabolism
		6.2.1: Phase I Biotransformation
			6.2.1.1: Oxidations
			6.2.1.2: Reductions
			6.2.1.3: Hydrolysis
		6.2.2: Phase II Biotransformation
			6.2.2.1: Uridine diphosphate-glucuronosyltransferases
			6.2.2.2: Glutathione S-transferases
			6.2.2.3: Methyltransferases
			6.2.2.4: N-Acetyltransferases
			6.2.2.5: Sulfotransferases
	6.3: Metabolism of Xenobiotics in Gut
		6.3.1: Luminal and Cell Wall Metabolism of Drugs
		6.3.2: Gut Microflora Implication in Xenobiotic Metabolism
			6.3.2.1: Reduction of drugs by microbiota
			6.3.2.2: Microbial metabolism of drugs by hydrolysis
	6.4: Conclusion
Chapter 7: Degradation of Pharmaceutically Active Compounds by White-Rot Fungi and Their Ligninolytic Enzymes
	7.1: Introduction
	7.2: PhAC Removal by WRF and Their Ligninolytic Enzymes
		7.2.1: Effect of Fungal Species
		7.2.2: Effect of Enzyme Types
		7.2.3: Effect of PhAC Properties on Their Removal
			7.2.3.1: Removal of PhACs containing EDGs
			7.2.3.2: Removal of PhACs containing EWGs
			7.2.3.3: Removal of PhACs containing both EDGs and EWGs
			7.2.3.4: Effect of hydrophobicity
		7.2.4: Laccase-Redox Mediator System
	7.3: Impact of Physicochemical Characteristics of Wastewater
	7.4: Treatment of Real Wastewater by WRF and Ligninolytic Enzymes
	7.5: Future Research
	7.6: Conclusion
Chapter 8: Removal of Pharmaceutical Pollutants from Municipal Sewage Mediated by Laccases
	8.1: Introduction
	8.2: Political and Societal Framework Conditions
		8.2.1: Situation in Germany
		8.2.2: Situation in Switzerland
	8.3: Elimination of Pharmaceuticals with Physical and Chemical Methods
		8.3.1: Use of Activated Carbon
			8.3.1.1: Granulated activated carbon
			8.3.1.2: Powdered activated carbon
		8.3.2: Use of Ozonation
		8.3.3: Combined and Other Treatment Processes
			8.3.3.1: Combined ozonation and activated carbon
			8.3.3.2: Combined ozone and hydrogen peroxide
			8.3.3.3: UV light
			8.3.3.4: Membrane filtration
	8.4: Theoretical Background and Application of Laccases
		8.4.1: Occurrence, Structure and Functionality of Laccases
			8.4.1.1: Origin and characterization
			8.4.1.2: Reaction mechanism and stoichiometry
			8.4.1.3: Substrates and products
			8.4.1.4: Inhibition of laccase activity
			8.4.1.5: Immobilization types for laccases
		8.4.2: Laccase-Mediator-System
		8.4.3: Industrial Use of Laccase
	8.5: Elimination of Pharmaceuticals by the Use of Laccase
	8.6: Comparison of Different Technologies for the Elimination of Pharmaceuticals
	8.7: Assessing the Use of Laccase in Municipal Wastewater Treatment
		8.7.1: Use of Native Laccases
		8.7.2: Use of Immobilized Laccase
	8.8: Summary and Conclusions towards Removal of Pharmaceuticals
Chapter 9: Mechanism of Drug Resistance in Staphylococcus aureus and Future Drug Discovery
	9.1: Introduction
	9.2: Drugs, Targets and Resistance Mechanism
	9.3: Future Drug Discovery and New Drugs
	9.4: Conclusion
Chapter 10: Genome Editing and Gene Therapies: Complex and Expensive Drugs
	10.1: Introduction
	10.2: Some General Aspects
	10.3: Genome Editing Techniques: Fundamentals
		10.3.1: Zinc Finger Nucleases
		10.3.2: TALENs
		10.3.3: CRISPR/Cas Systems
			10.3.3.1: Other applications of CRISPR-systems
	10.4: Therapeutic Genome Editing
		10.4.1: HDR-Mediated Genome Editing
		10.4.2: Ex vivo and in vivo Somatic Genome Editing
		10.4.3: Delivery Strategies
			10.4.3.1: Adeno-associated viral vectors
			10.4.3.2: Lentiviral vectors
			10.4.3.3: Nanocarrier-based gene/drug delivery
			10.4.3.4: Physical methods
		10.4.4: Genome Editing and Disease Models
		10.4.5: Induced Pluripotent Stem Cells
			10.4.5.1: Human diseases: From 2D to 3D iPSC models
			10.4.5.2: Genome editing and human iPSCs
		10.4.6: Genome Editing and Diseases
			10.4.6.1: Genome editing studies in non-clinical development and clinical trials
			10.4.6.2: Examples of non-clinical developments
			10.4.6.3: CAR-T cell therapy and CRISPR
		10.4.7: Gene Therapies without Modifying the Existing DNA
		10.4.8: Genome Editing-Based Therapeutics in Clinical Trials and Off-Target Effects
			10.4.8.1: Off-target effects
		10.4.9: Genome Editing: Commercialization
		10.4.10: Ethical Concerns and Regulatory Aspects
	10.5: Summary and Outlook
Chapter 11: Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
	11.1: Introduction
	11.2: Epigenetic Alterations in Human Cancers
	11.3: Metabolic Alterations in Human Cancers
	11.4: Interplay between Epigenetics and Tumor Metabolism
		11.4.1: Modulation of Epigenetics by Tumor Metabolism
		11.4.2: Acetyl-CoA Influences Histone Acetylation
		11.4.3: SAM/SAH Ratio Regulates DNA and Histone Methylation
		11.4.4: TCA Cycle Metabolites Modulate DNA and Histone Demethylation
		11.4.5: Succinate and Fumarate drive DNA/Histone Methylation
		11.4.6: 2-Hydroxylglutarate in IDH1/IDH2 Mutant Cancers Drive DNA/Histone Methylation
	11.5: Therapeutic Approaches
		11.5.1: Inhibition of Acetyl-CoA Production Using Glycolysis Inhibitors
		11.5.2: Inhibition of Succinate/Fumarate/2-Hydroxylglutarate Using Glutaminolysis Inhibitors
		11.5.3: Inhibition of 2-Hydroxylglutarate Using IDH1/2 Inhibitors
		11.5.4: Inhibition of One Carbon Metabolism by Limiting Methionine Cycle
		11.5.5: Inhibition of DNA Methylation by DNMTs
		11.5.6: Inhibition of Tumor Metabolism by HDACi
	11.6: Conclusion
Index