Pharmaceutical Biocatalysis: Drugs, Genetic Diseases, and Epigenetics

Description

Volume 7 of the Jenny Stanford Series on Biocatalysis deals with several different aspects of pharmaceuticals, which include not only various applications of drugs and their metabolism but also natural resources for active pharmaceutical ingredients as well as the removal of pharmaceutical pollution. In detail, novel approaches for developing microbial fermentation processes to produce vitamin B6 using microorganisms are described together with novel routes for vitamin B6 biosynthesis. The other topics discussed are new approaches for producing the successful anticancer drug Taxol from naturally occurring precursors, molecular farming through plant engineering as a cost-effective means to produce therapeutic and prophylactic proteins, and successful screening of potent microorganisms producing L-asparaginase for various chemotherapeutic applications. Furthermore, microbial biotransformations in the production and degradation of fluorinated pharmaceuticals are described. The other chapters inform the reader about the biotransformation of xenobiotics/drugs in living systems, the degradation of pharmaceuticals by white-rot fungi and their ligninolytic enzymes, and the removal of pharmaceutical pollution from municipal sewage using laccase. 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