Pharmaceutical Biocatalysis

This book provides an overview of the world market of therapeutic enzymes and enzyme inhibitors, rare diseases, orphan drugs, the costs of drug development and therapies, and enzymes in downstream processing of pharmaceuticals. It discusses carbonic anhydrase inhibitors and their multiple drug interactions, carboxylesterase inhibitors for pharmaceutical applications, employment of inhibitors for the treatment of neurodegenerative diseases, use of engineered proteins, bioactive peptides, and fibrinolytic enzymes for thrombolytic therapy, and enzymes important for the design and development of new drugs/drug metabolites such as aldehyde oxidases and cytochrome P450 enzymes and the role the latter play in vascular biology and pathophysiology. The treatment of cancer is explored in connection with enzymatic amino acid deprivation therapies and new drugs that act as chemical degraders of oncogenic proteins. The book also introduces the resistance mechanisms of cancer. Furthermore, it provides an insight into the relationship between pathological conditions of cardiovascular disease and oxidative stress. The text also focuses on the potential use of nanoparticles as carriers for enzymes with medical relevance, computer-aided drug design for the identification of multi-target directed ligands, and the development of improved therapeutics through a glycan-“designer” approach. It concludes with an introduction to the chemoenzymatic synthesis of drugs.

This volume provides an insight into the future strategies for commercial biocatalysis with a focus on sustainable technologies, together with chemoenzymatic and biotechnological approaches to synthesize various types of approved and new active pharmaceutical ingredients (APIs) via proven and latest synthetic routes using single-step biocatalytic or enzyme cascade reactions. Many of these drugs act as enzyme inhibitors, as discussed in a chapter with a variety of examples. The targeted enzymes are involved in diseases such as different cancers, metastatic and infectious diseases, osteoporosis, and cardiovascular disorders. The biocatalysts employed for API synthesis include hydrolytic enzymes, alcohol dehydrogenases, laccases, imine reductases, reductive aminases, peroxygenases, cytochrome P450 enzymes, polyketide synthases, transaminases, and halogenases. Many of them have been improved with respect to their properties by engineering methods. The book discusses the syntheses of drugs, including alkaloids and antibiotics, non-ribosomal peptides, antimalarial and antidiabetic drugs, prenylated xanthones, antioxidants, and many important (chiral) intermediates required for the synthesis of pharmaceuticals.

This volume of Pharmaceutical Biocatalysis starts with a discussion on the importance of biocatalytic synthesis approaches for a sustainable and environmentally friendly production of pharmaceuticals and active pharmaceutical ingredients. Among the enzymes discussed in detail with respect to their pharmaceutical relevance are cyclic nucleotide phosphodiesterases playing an important role in modulating signal transduction in various cell types; human DOPA decarboxylase, related to Parkinson's disease and aromatic amino acid decarboxylase deficiency; and phospholipase D enzymes as drug targets. Isocitrate dehydrogenase 1 and 2 mutations are novel therapeutic targets in acute myeloid leukemia. An additional chapter is devoted to the use of enzymes for prodrug activation in cancer therapy. The other topics include small-molecule inhibitors targeting receptor tyrosine kinases in cancer, β-Lactams and related compounds as antibacterials, non-vitamin K oral anticoagulants for the treatment of thromboembolic diseases, and the molecular mechanisms for statin pleiotropy and its clinical relevance in cardiovascular diseases. The last chapter is a review of lysosomal storage disorders with an overview of approved drugs for treating these disorders by enzyme replacement therapy.

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.

Because enzyme-catalyzed reactions exhibit higher enantioselectivity, regioselectivity, substrate specificity, and stability, they require mild conditions to react while prompting higher reaction efficiency and product yields. Biocatalysis in the Pharmaceutical and Biotechnology Industries examines the use of catalysts to produce fine chemicals and chiral intermediates in a variety of pharmaceutical, agrochemical, and other biotechnological applications. Written by internationally recognized scientists in biocatalysis, the authors analyze the synthesis of chiral intermediates for over 60 brand-name pharmaceuticals for a wide range of drug therapies and treatments. From starting material to product, the chapters offer detailed mechanisms that show chiral intermediates and other by-products for each reaction—including hydrolytic, acylation, halogenation, esterification, dehalogenation, oxidation-reduction, oxygenation, hydroxylation, deamination, transamination, and C–C, C–N, C–O bonds formation. Cutting-edge topics include advanced methodologies for gene shuffling and directed evolution of biocatalysts; the custom engineering of enzymes; the use of microbial cells and isolated biocatalysts; the use of renewable starting materials; and generating novel molecules by combinatorial biocatalysis and high-throughput screening. Focusing on industrial applications, the book also considers factors such as bulk processes, instrumentation, solvent selection, and techniques for catalyst immobilization, reusability, and yield optimization throughout. Biocatalysis in the Pharmaceutical and Biotechnology Industries showcases the practical advantages and methodologies for using biocatalysts to develop and produce chiral pharmaceuticals and fine chemicals.

This book provides an overview of the world market of therapeutic enzymes and enzyme inhibitors, rare diseases, orphan drugs, the costs of drug development and therapies, and enzymes in downstream processing of pharmaceuticals. It discusses carbonic anhydrase inhibitors and their multiple drug interactions, carboxylesterase inhibitors for pharmaceutical applications, employment of inhibitors for the treatment of neurodegenerative diseases, use of engineered proteins, bioactive peptides, and fibrinolytic enzymes for thrombolytic therapy, and enzymes important for the design and development of new drugs/drug metabolites such as aldehyde oxidases and cytochrome P450 enzymes and the role the latter play in vascular biology and pathophysiology. The treatment of cancer is explored in connection with enzymatic amino acid deprivation therapies and new drugs that act as chemical degraders of oncogenic proteins. The book also introduces the resistance mechanisms of cancer. Furthermore, it provides an insight into the relationship between pathological conditions of cardiovascular disease and oxidative stress. The text also focuses on the potential use of nanoparticles as carriers for enzymes with medical relevance, computer-aided drug design for the identification of multi-target directed ligands, and the development of improved therapeutics through a glycan-“designer” approach. It concludes with an introduction to the chemoenzymatic synthesis of drugs.

Biocatalysis is rapidly evolving into a key technology for the discovery and production of chemicals, especially in the pharmaceutical industry, where high yielding chemo-, regio-, and enantioselective reactions are critical. Taking the latest breakthroughs in genomics and proteomics into consideration, Biocatalysis for the Pharmaceutical Industry concisely yet comprehensively discusses the modern application of biocatalysis to drug discovery, development, and manufacturing. Written by a team of leading experts, the book offers deep insight into this cutting edge field. Covers a wide range of topics in a systematic manner with an emphasis on industrial applications Provides a thorough introduction to the latest biocatalysts, modern expression hosts, state-of-the-art directed evolution, high throughput screening, and bioprocess engineering Addresses frontier subjects such as emerging enzymes, metabolite profiling, combinatorial biosynthesis, metabolic engineering, and autonomous enzymes for the synthesis and development of chiral molecules, drug metabolites, and semi-synthetic medicinal compounds and natural product analogs Highlights the impact of biocatalysis on green chemistry Contains numerous graphics to illustrate concepts and techniques Biocatalysis for the Pharmaceutical Industry is an essential resource for scientists, engineers, and R&D policy makers in the fine chemical, pharmaceutical, and biotech industries. It is also an invaluable tool for academic researchers and advanced students of organic and materials synthesis, chemical biology, and medicinal chemistry.

This volume provides an insight into the future strategies for commercial biocatalysis with a focus on sustainable technologies, together with chemoenzymatic and biotechnological approaches to synthesize various types of approved and new active pharmaceutical ingredients (APIs) via proven and latest synthetic routes using single-step biocatalytic or enzyme cascade reactions. Many of these drugs act as enzyme inhibitors, as discussed in a chapter with a variety of examples. The targeted enzymes are involved in diseases such as different cancers, metastatic and infectious diseases, osteoporosis, and cardiovascular disorders. The biocatalysts employed for API synthesis include hydrolytic enzymes, alcohol dehydrogenases, laccases, imine reductases, reductive aminases, peroxygenases, cytochrome P450 enzymes, polyketide synthases, transaminases, and halogenases. Many of them have been improved with respect to their properties by engineering methods. The book discusses the syntheses of drugs, including alkaloids and antibiotics, non-ribosomal peptides, antimalarial and antidiabetic drugs, prenylated xanthones, antioxidants, and many important (chiral) intermediates required for the synthesis of pharmaceuticals.