Download or read book Chemoenzymatic Synthesis of Polyketide Natural Products written by Taylor P. A. Hari and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Polyketide secondary metabolites constitute a structurally-diverse and clinically-important family of natural products. The wide range of biological activities represented by these substrates have contributed to therapeutic agents with annual sales exceeding $20B USD. Large multi-domain proteins called polyketide synthases (PKSs) use simple building blocks to generate highly-oxygenated and stereochemically-rich frameworks with astonishing selectivity. These substrates often feature rigidifying biases imposed by macrocyclic lactones and substituted heterocycles, which can impact their bioactive conformation. The work of this dissertation combines synthetic chemistry and biochemistry to investigate chemoenzymatic production of macrocyclic polyketide natural products. Research focused on validating a transannular oxa-conjugate addition strategy to assembly 2,6-cis-tetrahydropyran (THP) ring systems, as demonstrated by synthesis of the macrocyclic core to neopeltolide. Ultimately, we wish to apply this chemistry to de novo PKS pathways for rapid, reliable, and sustainable production of THP-bearing products like neopeltolide, and toward building SAR libraries. Additionally, a second study probed the specificity of the macrolactonizing thioesterase (TE) domain from the 6-deoxyerythronolide B (DEBS) biosynthetic pathway. This pathway is the paradigm for type-I PKS systems, and is responsible for producing the macrolide core of erythromycin. Our on-going research evaluates the limits of promiscuity within this specific catalytic domain, to characterize the structural elements required to accurately predict macrolactonization. The long-term goal of this study is to assess the potential applicability of DEBS TE as a generalized cyclization biocatalyst for combinatorial biochemistry and chemoenzymatic research.
Download or read book Natural Products via Enzymatic Reactions written by Jörn Piel and published by Springer Science & Business Media. This book was released on 2010-10-21 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Key Building Blocks via Enzyme-Mediated Synthesis, by Thomas Fischer and Jörg Pietruszka * Engineered Biosynthesis of Plant Polyketides: Structure-Based and Precursor-Directed Approach, by Ikuro Abe * Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others, by Joachim Stöckigt, Zhong Chen, and Martin Ruppert * Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products, by Bohdan Ostash, Xiaohui Yan, Victor Fedorenko, and Andreas Bechthold * Total (Bio)Synthesis: Strategies of Nature and of Chemists, by Alexandra A. Roberts, Katherine S. Ryan, Bradley S. Moore, and Tobias A.M. Gulder
Download or read book Synthesis and Biosynthesis of Polyketide Natural Products written by Atahualpa Pinto and published by . This book was released on 2011 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Chemical and Biological Synthesis written by Nick J Westwood and published by Royal Society of Chemistry. This book was released on 2018-08-16 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: Synthetic chemistry plays a central role in many areas of chemical biology; utilising recent case studies, the goal of Chemical and Biological Synthesis is to highlight the full impact that the preparation of novel reagents can have in chemical biology. Covering the synthetic approaches that can be applied across the whole field of chemical biology, this book provides synthetic chemists with the broader context to which their work contributes and the biological questions that can be addressed through it. An ideal guide for postgraduate students and researchers in synthetic organic chemistry and chemical biology, Chemical and Biological Synthesis introduces synthetic techniques and methods to those who wish to incorporate synthesis for the first time in their biology-focused research programmes.
Download or read book New Strategies for the Synthesis of Polyketide Natural Products written by Alessandra Polara and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Efforts Toward an Oxa conjugate Addition Based Approach to Neopeltolide Synthesis written by Taylor P. A. Hari and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: (+)-Neopeltolide is a highly potent marine polyketide natural product with activity against multiple cancer cell lines in vitro. The nanomolar range of antifungal and anticancer cytotoxicity in this tetrahydropyran (THP)-containing polyketide, combined with its limited natural supply, has led to several syntheses. In this study, the feasibility of an oxa-Michael conjugate addition route to cis-2,6-THP rings is examined through the efforts toward a total synthesis of the macrocyclic core of (+)-neopeltolide using a highly convergent route. This study is based on the successful preliminary results with a simple 14-member ring model system and the synthesis of the key aldehyde intermediate shown below. The highlighted transformation of this synthesis will be a transannular oxa-conjugate addition to generate the cis-2,6-tetrahydropyran ring system. This route also highlights a highly convergent Wittig coupling to generate the full carbon framework of (+)-neopeltolide. One of the key goals of this project is to compare this synthesis with a chemo-enzymatic total synthesis that relies on chemistry catalyzed by polyketide synthase enzymes in the late stage of the synthesis.
Download or read book Chemoenzymatic synthesis of chromodepsipeptides and natural product discovery via genome mining written by Lars Robbel and published by . This book was released on 2010 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Flavin Dependent Enzymes Mechanisms Structures and Applications written by and published by Academic Press. This book was released on 2020-09-21 with total page 568 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Enzymes, Volume 47, highlights new advances in the field, with this new volume presenting interesting chapters on The Multipurpose Family of Oxidases, Vanillyl alcohol oxidase, Choline oxidases, Aryl alcohol oxidase, D- and L-amino acid oxidases, Sugar oxidases, Phenolic Compounds hydroxylases, Baeyer-Villiger Monooxygenases, Flavin-dependent halogenases, Flavin-dependent dehalogenases, Styrene Monooxygenases, Bacterial luciferases, Cellobiose Dehydrogenases, Prenylated flavoenzymes, Ene-reductases, Flavoenzymes in Biocatalysis. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in The Enzymes series
Download or read book Towards Preparative in Vitro Enzymatic Synthesis of New Polyketide Metabolites written by Amanda Jane Hughes and published by . This book was released on 2013 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Modular polyketide synthases (PKSs) are the largest enzymes known to man and are responsible for synthesizing some of the most important human medicines. Their ability to construct stereochemically-rich carbon chains containing diverse substituents has inspired the biosynthetic community to engineer these factories for the in vitro synthesis of a small library of polyketide compounds. New complex polyketides are discovered every year, yet the lack of compound prohibits characterization and testing of these new compounds for medicinal properties. Smaller polyketide compounds generated in vitro could be organically manipulated to generate larger, more complex polyketide natural products and natural product analogs. Chemoenzymatic approaches like this would be extremely beneficial to the scientific community; however, there are still obstacles that must be overcome before the use of PKS for the preparative synthesis of an in vitro generated polyketide library would prove fruitful: purchasing substrates such as methylmalonyl-CoA is cost-prohibitive, PKSs are often difficult to express and purify, and the products generated are typically nonchromophoric. The use of a malonyl-CoA ligase from Streptomyces coelicolor (MatB) was investigated for the enzymatic synthesis of polyketide extender units such as methylmalonyl-CoA (Chapter 2). MatB synthesized a total of 5 CoA-linked extender units in vitro: malonyl-, methylmalonyl-, ethylmalonyl-, hydroxymalonyl- and methoxymalonyl-CoA. Two ternary complex structures of MatB with bound product and leaving group were also solved to sub-2Å resolution. MatB generated extender units were employed in the module-catalyzed synthesis of a triketide pyrone. The selectivity of a PKS module to incorporate a variety of side chains into triketide pyrones was also investigated (Chapter 3). A total of 10 triketide pyrone compounds were synthesized, 5 produced via modular "stuttering" and one possessing a terminal alkyne chemical handle. Lastly, nonchromphoric polyketide products were made visible upon copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) with fluorescent sulforhodamine B azide revealing insights into in vitro reactivites of a PKS module (Chapter 4). The work described in this dissertation has helped advance the scientific community towards procuring an in vitro synthesized polyketide library for future synthetic applications.
Download or read book Comprehensive Natural Products II written by and published by Elsevier. This book was released on 2010-03-05 with total page 7944 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work presents a definitive interpretation of the current status of and future trends in natural products—a dynamic field at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids, and enzymes. With more than 1,800 color figures, Comprehensive Natural Products II features 100% new material and complements rather than replaces the original work (©1999). Reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine Stimulates new ideas among the established natural products research community—which includes chemists, biochemists, biologists, botanists, and pharmacologists Informs and inspires students and newcomers to the field with accessible content in a range of delivery formats Includes 100% new content, with more than 6,000 figures (1/3 of these in color) and 40,000 references to the primary literature, for a thorough examination of the field Highlights new research and innovations concerning living organisms and their distinctive role in our understanding and improvement of human health, genomics, ecology/environment, and more Adds to the rich body of work that is the first edition, which will be available for the first time in a convenient online format giving researchers complete access to authoritative Natural Products content
Download or read book Medicinal Natural Products written by Paul M. Dewick and published by John Wiley & Sons. This book was released on 2002-01-03 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: This guide covers classes of natural products in medicine, whether derived from plants, micro-organisms or animals. Structured according to biosynthetic pathway, it is written from a chemistry-based approach.
Download or read book Pharmaceutical Biocatalysis written by Peter Grunwald and published by CRC Press. This book was released on 2019-11-07 with total page 567 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Synthesis of Polyketide Derived Natural Products and Putative Biosynthetic Intermediates written by Chengsen Cui and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Complex Enzymes in Microbial Natural Product Biosynthesis Part B Polyketides Aminocoumarins and Carbohydrates written by and published by Academic Press. This book was released on 2009-04-11 with total page 644 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microbial natural products have been an important traditional source of valuable antibiotics and other drugs but interest in them waned in the 1990s when big pharma decided that their discovery was no longer cost-effective and concentrated instead on synthetic chemistry as a source of novel compounds, often with disappointing results. Moreover understanding the biosynthesis of complex natural products was frustratingly difficult. With the development of molecular genetic methods to isolate and manipulate the complex microbial enzymes that make natural products, unexpected chemistry has been revealed and interest in the compounds has again flowered. This two-volume treatment of the subject will showcase the most important chemical classes of complex natural products: the peptides, made by the assembly of short chains of amino acid subunits, and the polyketides, assembled from the joining of small carboxylic acids such as acetate and malonate. In both classes, variation in sub-unit structure, number and chemical modification leads to an almost infinite variety of final structures, accounting for the huge importance of the compounds in nature and medicine. Gathers tried and tested methods and techniques from top players in the field Provides an extremely useful reference for the experienced research scientist Covers biosynthesis of Polyketides, Tarpenoids, Aminocoumarins and Crabohydrates
Download or read book Chemoenzymatic Formation of Hydroxypiperidines written by Maria Antonia Wijdeven and published by . This book was released on 2010 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Natural Product Biosynthesis written by Christopher T. Walsh and published by Royal Society of Chemistry. This book was released on 2017-04-28 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook describes the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era.
Download or read book Application of Asymmetric Catalysis for the Synthesis and Medicinal Chemistry Study of Polyketide Natural Products written by Yanping Wang and published by . This book was released on 2014 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most polyketide natural products are chiral and exist in enantiomerically pure form, often containing more than one stereogenic centers. During synthesis of the polyketide natural products, these centers can be either derived from nature's chiral pools or from resolution of racemic mixtures. Alternatively, the chiral center can be installed using asymmetric catalysis. The asymmetric catalysis approach has the potential to be the most efficient strategy for the construction of libraries of stereochemical polyketide natural products by the installation stereochemistry into the achiral starting materials. Asymmetric catalysis was used to synthesize two categories of polyketide natural products, cryptocaryols and tetrahydrolipstatin, in 25 and 10 longest linear steps, respectively. In addition, five cryptocaryol and eight tetrahydrolipstatin stereochemical analogues were also accessed, which demonstrated the versatility of the catalytic asymmetric approach. The asymmetric catalysis strategy is also applied to an ongoing project the total synthesis of EBC-23. These stereochemical analogues were used to develop structure activity relationship profiles for cryptocaryols and tetrahydrolipstatin cytotoxicity against cancer cell lines (e.g. MCF-7 and H460).
