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Author: Roland David Kersten Publisher: ISBN: 9781303212000 Category : Languages : en Pages : 233
Book Description
Scientific progress in organic synthesis, biochemistry and biology and cures to many infectious diseases and cancer rely on discovery of microbial natural products and their biosynthetic pathways. `Omics' approaches such as genome mining have opened new opportunities for natural product discovery within the last decade as ~90% of pathways in microbial genomes are uncharacterized in their products. Genome mining for natural product discovery can be defined as the connection of a natural product (chemotype) with its biosynthetic genes (genotype) by applied biosynthetic knowledge. Traditional genome mining approaches are in silico-guided approaches in which the isolation of a new natural product is guided by bioinformatic predictions from a target cryptic gene cluster. The problem of in silico-guided genome mining in natural product discovery is its low-throughput rate as only one pathway is characterized per experiment. In this dissertation, mass spectrometry (MS)-guided genome mining approaches are introduced which rapidly connect a natural product with its biosynthetic genes by matching de novo tandem MS structures of biosynthetic building blocks such as amino acids and sugars to metabolite structures predicted from microbial genomes. As MS guided genome mining starts at the chemotype level by e.g. liquid chromatography-tandem mass spectrometry analysis of a microbial extract and subsequently connects putative natural products with their gene clusters, it has the potential for automation. In Chapter 2, peptidogenomics is introduced as a MS-guided genome mining approach for characterization of ribosomal and nonribosomal peptide chemotypes and their corresponding genotypes. Peptidogenomics characterized ten new peptide chemo- and genotypes from Streptomyces cultures including lanthipeptides, lassopeptides, linaridins and lipopeptides. In Chapter 3, a combination of imaging mass spectrometry, tandem MS and genome mining characterized the biosynthetic pathway of the didemnin anti-cancer agents in the marine alpha-proteobacterium Tistrella mobilis. In Chapter 4, glycogenomics is introduced as a MS-guided genome mining approach to connect chemo- and genotypes of glycosylated natural products. Glycogenomics enabled the discovery of putative arenimycin B, a glycosylated aromatic polyketide from the marine actinobacterium Salinispora arenicola and its biosynthetic pathway. In Chapter 5, bioactivity-guided genome mining combined with genetic knockouts and glycogenomics characterized the biosynthetic gene cluster of the lomaiviticins anti cancer agents in the marine actinobacterium Salinispora tropica.
Author: Roland David Kersten Publisher: ISBN: 9781303212000 Category : Languages : en Pages : 233
Book Description
Scientific progress in organic synthesis, biochemistry and biology and cures to many infectious diseases and cancer rely on discovery of microbial natural products and their biosynthetic pathways. `Omics' approaches such as genome mining have opened new opportunities for natural product discovery within the last decade as ~90% of pathways in microbial genomes are uncharacterized in their products. Genome mining for natural product discovery can be defined as the connection of a natural product (chemotype) with its biosynthetic genes (genotype) by applied biosynthetic knowledge. Traditional genome mining approaches are in silico-guided approaches in which the isolation of a new natural product is guided by bioinformatic predictions from a target cryptic gene cluster. The problem of in silico-guided genome mining in natural product discovery is its low-throughput rate as only one pathway is characterized per experiment. In this dissertation, mass spectrometry (MS)-guided genome mining approaches are introduced which rapidly connect a natural product with its biosynthetic genes by matching de novo tandem MS structures of biosynthetic building blocks such as amino acids and sugars to metabolite structures predicted from microbial genomes. As MS guided genome mining starts at the chemotype level by e.g. liquid chromatography-tandem mass spectrometry analysis of a microbial extract and subsequently connects putative natural products with their gene clusters, it has the potential for automation. In Chapter 2, peptidogenomics is introduced as a MS-guided genome mining approach for characterization of ribosomal and nonribosomal peptide chemotypes and their corresponding genotypes. Peptidogenomics characterized ten new peptide chemo- and genotypes from Streptomyces cultures including lanthipeptides, lassopeptides, linaridins and lipopeptides. In Chapter 3, a combination of imaging mass spectrometry, tandem MS and genome mining characterized the biosynthetic pathway of the didemnin anti-cancer agents in the marine alpha-proteobacterium Tistrella mobilis. In Chapter 4, glycogenomics is introduced as a MS-guided genome mining approach to connect chemo- and genotypes of glycosylated natural products. Glycogenomics enabled the discovery of putative arenimycin B, a glycosylated aromatic polyketide from the marine actinobacterium Salinispora arenicola and its biosynthetic pathway. In Chapter 5, bioactivity-guided genome mining combined with genetic knockouts and glycogenomics characterized the biosynthetic gene cluster of the lomaiviticins anti cancer agents in the marine actinobacterium Salinispora tropica.
Author: Cheng-Hsuan Wu Publisher: ISBN: 9781267904751 Category : Languages : en Pages : 113
Book Description
Genome mining has become an invaluable approach in aiding the discovery of peptide natural products; a large and diverse group of potentially bioactive molecules. Here we propose nanoDESI based MS/MS networking to map the searchable molecular universe of a large number of strains. The organization of the molecular universe via MS/MS networking enables molecular family guided genome mining to connect NRPS molecular families produced by unsequenced organisms to candidate gene cluster families found in publicly available genome databases. As proof-of-principle, we collected nanoDESI MS/MS data on 42 bacilli and 17 pseudomonads and used molecular MS/MS networking to identify the peptidic products through generation of amino acid sequence tags from the MS/MS data. Furthermore, we use these studied dataset to identify unknown molecules from unsequenced microbes.
Author: Taícia Pacheco Fill Publisher: Springer Nature ISBN: 3031417410 Category : Science Languages : en Pages : 256
Book Description
This book focuses on the importance of omics strategies and de-replication analysis to unveil new molecules from microbial sources with diverse chemical structures and biological functions. Chapters address metabolomics strategies, which will lead to a better understanding of the chemical interactions between microorganisms, plant-microorganisms, and virus-microorganisms. Authors also describe analytical tools used in microbial metabolomics and natural products discovery, in addition to describing a step-by-step protocol to identify and annotate metabolites using various databases and online platforms. The book presents the newest research, tools, and protocols for chemists, biochemists, bio-and chemical engineers, and biotechnologists, among others.
Author: Publisher: Elsevier ISBN: 0081026919 Category : Science Languages : en Pages : 4266
Book Description
Comprehensive Natural Products III, Third Edition, Seven Volume Set updates and complements the previous two editions, including recent advances in cofactor chemistry, structural diversity of natural products and secondary metabolites, enzymes and enzyme mechanisms and new bioinformatics tools. Natural products research is a dynamic discipline 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. This book reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine and to stimulate new ideas among the established natural products community. Provides readers with an in-depth review of current natural products research and a critical insight into the future direction of the field Bridges the gap in knowledge by covering developments in the field since the second edition published in 2010 Split into 7 sections on key topics to allow students, researchers and professionals to find relevant information quickly and easily Ensures that the knowledge within is easily understood by and applicable to a large audience
Author: Yanyan Li Publisher: Springer ISBN: 1493910108 Category : Medical Languages : en Pages : 113
Book Description
Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.
Author: Atta-ur-Rahman Publisher: Bentham Science Publishers ISBN: 1681083698 Category : Science Languages : en Pages : 236
Book Description
Frontiers in Clinical Drug Research - Anti infectives is an eBook series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the treatment of infectious diseases. The scope of the eBook series covers a range of topics including the chemistry, pharmacology, molecular biology and biochemistry of natural and synthetic drugs employed in the treatment of infectious diseases. Reviews in this series also include research on multi drug resistance and pre-clinical / clinical findings on novel antibiotics, vaccines, antifungal agents and antitubercular agents. Frontiers in Clinical Drug Research – Anti infectives is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critically important information for developing clinical trials and devising research plans in the field of anti infective drug discovery and epidemiology. The third volume of this series features reviews that cover a variety of topics including: -Geomic mining and metabolomic techniques for developing antimcrobials -Probiotic use in complementary antiretroviral therapy -Anti-HIV pharmaceuticals -Phytochemicals used for antimicrobial purposes - Antimicrobial photodynamic therapy (APDT)
Author: Lesley-Ann Giddings Publisher: Springer ISBN: 3319148362 Category : Science Languages : en Pages : 63
Book Description
This SpringerBrief sheds new light on bioactive materials from extremophiles with the focus on the biosynthesis processes and related genomics. It deals with all aspects of the chemical compounds produced by organisms living under extreme conditions that may have potential as drugs or lead to novel drugs for human use.
Author: Frank Petersen Publisher: Springer Science & Business Media ISBN: 3764381175 Category : Medical Languages : en Pages : 380
Book Description
In a real tour de force of pharmacological literature, this edited volume’s chapters highlight the biodiversity-driven approaches which are now of eminent importance in natural products research. It addresses the question why natural products display such complex chemical information, what makes them unique, as they often are, and what their characteristics are. Practical questions such as supply of natural substances and production optimization strategies are also covered.
Author: Learn-Han Lee Publisher: Frontiers Media SA ISBN: 2889636399 Category : Languages : en Pages : 312
Book Description
There is a large market demand for new drugs. The existing chronic or common ailments without cures, development of new diseases with unknown causes, and the widespread existence of antibiotic-resistant pathogens, have driven this field of research further by looking at all potential sources of natural products. To date, microbes have made a significant contribution to the health and well-being of people globally. The discoveries of useful metabolites produced by microbes have resulted in a significant proportion of pharmaceutical products in today’s market. Therefore, the investigation and identification of bioactive compound(s) producing microbes is always of great interest to researchers. Actinobacteria are one of the most important and efficient groups of natural metabolite producers. Among the numerous genera, Streptomyces have been recognized as prolific producers of useful natural compounds, as they provide more than half of the naturally-occurring antibiotics isolated to-date and continue to emerge as the primary source of new bioactive compounds. Certainly, these potentials have attracted ample research interest and a wide range of biological activities have been subsequently screened by researchers with the utilization of different In vitro and In vivo model of experiments. Literature evidence has shown that a significant number of interesting compounds produced by Actinobacteria were exhibiting either strong anticancer or neuroprotective activity. The further in depth studies have then established the modulation of apoptotic pathway was involved in those observed bioactivities. These findings indirectly prove the biopharmaceutical potential possessed by Actinobacteria and at the same time substantiate the importance of diverse pharmaceutical evaluations on Actinobacteria. In fact, many novel compounds discovered from Actinobacteria with strong potential in clinical applications have been developed into new drugs by pharmaceutical companies. Together with the advancement in science and technology, it is predicted that there would be an expedition in discoveries of new bioactive compounds producing Actinobacteria from various sources, including soil and marine sources. In light of these current needs, and great interest in the scope of this research, this book seeks to contribute on the investigation of different biological active compound(s) producing actinobacteria which are exhibiting antimicrobial, antioxidant, neuroprotective, anticancer activities and similar.
Author: Loganathan Karthik Publisher: Springer Nature ISBN: 9811658358 Category : Science Languages : en Pages : 285
Book Description
This book summarizes the basics of actinobacteria, from microbiology to synthetic biology. It focuses on diversity, NRPS, sesquiterpenes, lantipeptide, bioinformatics apparatuses, cloning, CRISPR, reverse engineering, FDA supported medications, and marine actinobacteria. It also covers the latest trends in drug discovery from actinobacteria, and introduces several recently developed bioinformatics and synthetic biology tools to explore new antibiotics from actinobacteria. Many natural products such as polyketides, isoprenoids, phenazines, peptides, indolocarbarbazoles, sterols, and others have been isolated and characterized from actinobacteria. Some products are synthesized by the non-ribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs), or other functional genes. Although genome sequencing has uncovered the differing qualities of these chemicals, recognizing new items and their biosynthetic pathways is still under examination. Cryptic metabolic pathways have been explored using molecular techniques or culture-dependent approaches. In recent years, researchers’ primary interest is to identify the specific conditions or agents that wake the cryptic antibiotics. Several bioinformatics and synthetic biology tools were developed to explore new antibiotics from actinobacteria. The book comprises 14 chapters with different aspects of application and utilization of actinomycetes from the microbiology; systems biology, pharmacology of natural products, bioinformatics, actinomycete and its diversity, CRISPR, artificial Intelligence, synthetic biology, metabolic engineering, expressional studies, and biosynthetic gene clusters. The book delivers useful information on actinomyces to researchers, novices in genome designing, specialists, clinicians, policymakers, and professionals.
Author: Roland David Kersten
Author: Roland David Kersten
Author: Cheng-Hsuan Wu
Author: Taícia Pacheco Fill
Author: 
Author: Yanyan Li
Author: Atta-ur-Rahman
Author: Lesley-Ann Giddings
Author: Frank Petersen
Author: Learn-Han Lee
Author: Loganathan Karthik