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Natural Products: Discourse, Diversity and Design provides an informative and accessible overview of discoveries in the area of natural products in the genomic era, bringing together advances across the kingdoms. As genomics data makes it increasingly clear that the genomes of microbes and plants contain far more genes for natural product synthesis than had been predicted from the numbers of previously identified metabolites, the potential of these organisms to synthesize diverse natural products is likely to be far greater than previously envisaged. Natural Products addresses not only the…mehr
Natural Products: Discourse, Diversity and Design provides an informative and accessible overview of discoveries in the area of natural products in the genomic era, bringing together advances across the kingdoms. As genomics data makes it increasingly clear that the genomes of microbes and plants contain far more genes for natural product synthesis than had been predicted from the numbers of previously identified metabolites, the potential of these organisms to synthesize diverse natural products is likely to be far greater than previously envisaged. Natural Products addresses not only the philosophical questions of the natural role of these metabolites, but also the evolution of single and multiple pathways, and how these pathways and products may be harnessed to aid discovery of new bioactives and modes of action. Edited by recognized leaders in the fields of plant and microbial biology, bioorganic chemistry and natural products chemistry, and with contributions from researchers at top labs around the world, Natural Products is unprecedented in its combination of disciplines and the breadth of its coverage. Natural Produces: Discourse, Diversity and Design will appeal to advanced students and experienced researchers, from academia to industry, in diverse areas including ecology, industrial biotechnology, drug discovery, medicinal chemistry, agronomy, crop improvement, and natural product chemistry.
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The editors Anne Osbourn is Professor at the University of East Anglia, UK, and Director of the Norwich Research Park Industrial Biotechnology and Bioenergy Alliance, and is based at the John Innes Centre. Rebecca J. Goss is Reader in Organic/Biomolecular Chemistry at the School of Chemistry and also at the Biomedical Sciences Research Complex at the University of St Andrews, UK. Guy T. Carter has over 30 years of experience working in Pharmaceutical R&D, primarily in the discovery and development of microbial products. He is currently CEO of Carter-Bernan Consulting and Chief Scientific Officer at Biosortia Pharmaceuticals, USA.
Inhaltsangabe
Contributors ix SECTION I NATURAL PRODUCTS IN THE NATURAL WORLD 1 Part 1 Role and Reason 3 1 The Role of Phytochemicals in Relationships of Plants with Other Organisms 5 Pawe³ Bednarek 2 Designer Microbial Ecosystems - Toward Biosynthesis with Engineered Microbial Consortia 23 David M. Babson, Mark Held, and Claudia Schmidt-Dannert 3 Marine Natural Products - Chemical Defense/Chemical Communication in Sponges and Corals 39 Elodie Qüevrain, Isabelle Domart-Coulon, and Marie-Lise Bourguet-Kondracki Part 2 Self-Protection - Avoiding Autotoxicity 67 4 How Plants Avoid the Toxicity of Self-Produced Defense Bioactive Compounds 69 Supaart Sirikantaramas, Mami Yamazaki, and Kazuki Saito Part 3 Fishing and Pharming 83 5 Marine Bioprospecting 85 Amanda M. Fenner and William H. Gerwick 6 Myxobacteria: Chemical Diversity and Screening Strategies 103 Alberto Plaza and Rolf M uller 7 Fungal Endophytes of Grasses and Morning Glories, and Their Bioprotective Alkaloids 125 Christopher L. Schardl, Li Chen, and Carolyn A. Young 8 Fungal-Actinomycete Interactions -Wakening of Silent Fungal Secondary Metabolism Gene Clusters via Interorganismic Interactions 147 Volker Schroeckh, Hans-Wilhelm N utzmann, and Axel A. Brakhage 9 Secondary Metabolites Produced by Plant Pathogens 159 Barbara J. Howlett SECTION II FROM GENES TO MOLECULES 171 Part 1 Reading the Genome 173 10 Analyzing Fungal Secondary Metabolite Genes and Gene Clusters 175 Yi-Ming Chiang, Clay C. C. Wang, and Berl R. Oakley Part 2 Biosynthesis and Heterologous Expression 195 11 RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptides 197 Noah A. Bindman and Wilfred A. Van Der Donk 12 Polyketide Synthase: Sequence, Structure, and Function 219 Joel Bruegger, Grace Caldara, Joris Beld, Michael D. Burkart, and Shiou-Chuan (Sheryl) Tsai 13 Manipulation of Fungal Natural Product Pathways 245 Russell J. Cox and Katherine Williams 14 Production of Therapeutic Products 261 Guojian Zhang and Blaine A. Pfeifer Part 3 Regulation: Waking Sleeping Pathways 277 15 Waking Sleeping Pathways in Filamentous Fungi 279 Joe Spraker and Nancy Keller SECTION III EVOLVING ENZYMES, EVOLVING PATHWAYS: SYNTHETIC BIOLOGY 293 Part 1 Chemical Diversification 295 16 The Oxidosqualene Cyclases: One Substrate, Diverse Products 297 Ikuro Abe 17 Harnessing Sugar Biosynthesis and Glycosylation to Redesign Natural Products and to Increase Structural Diversity 317 Carlos Olano, Carmen M endez, and Jos e A. Salas Part 2 Evolving Pathways 341 18 Evolutionary Mechanisms Involved in Development of Fungal Secondary Metabolite Gene Clusters 343 Geromy G. Moore, J er^ome Collemare, Marc-Henri Lebrun, and Rosie E. Bradshaw Part 3 Synthetic Biology 357 19 Synthetic Biology of Natural Products 359 Rainer Breitling and Eriko Takano SECTION IV SCREENING FOR BIOACTIVITY 371 20 Image-Based Screening Approaches to Natural Products Discovery 373 Christopher J. Schulze and Roger G. Linington 21 Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs 397 David J. Newman and Gordon M. Cragg 22 Is There an Ideal Database for Natural Products Research? 413 John W. Blunt and Murray H. G. Munro SECTION V TO APPLICATION 433 Case Studies 435 23 Daptomycin and A54145: Structure-Activity Relationship (SAR) Studies Enabled by Combinatorial Biosynthesis 437 Richard H. Baltz 24 Discovery and Development of NVB302, a Semisynthetic Antibiotic for Treatment of Clostridium difficile Infection 455 Steven Boakes and Michael J. Dawson 25 ILS-920: A Rapamycin Analog for Ischemic Stroke 469 Edmund I. Graziani 26 BC265: A Nonquinone Ansamycin Hsp90 Inhibitor Developed Using Biosynthetic Medicinal Chemistry 483 Matthew A. Gregory, Steven J. Moss, and Barrie Wilkinson 27 Discovery and Development of Caspofungin (CANCIDAS): Concept to Clinic 497 James M. Balkovec, David L. Hughes, Prakash S. Masurekar, Carole A. Sable, Robert E. Schwartz, and Sheo B. Singh Index 523
Contributors ix SECTION I NATURAL PRODUCTS IN THE NATURAL WORLD 1 Part 1 Role and Reason 3 1 The Role of Phytochemicals in Relationships of Plants with Other Organisms 5 Pawe³ Bednarek 2 Designer Microbial Ecosystems - Toward Biosynthesis with Engineered Microbial Consortia 23 David M. Babson, Mark Held, and Claudia Schmidt-Dannert 3 Marine Natural Products - Chemical Defense/Chemical Communication in Sponges and Corals 39 Elodie Qüevrain, Isabelle Domart-Coulon, and Marie-Lise Bourguet-Kondracki Part 2 Self-Protection - Avoiding Autotoxicity 67 4 How Plants Avoid the Toxicity of Self-Produced Defense Bioactive Compounds 69 Supaart Sirikantaramas, Mami Yamazaki, and Kazuki Saito Part 3 Fishing and Pharming 83 5 Marine Bioprospecting 85 Amanda M. Fenner and William H. Gerwick 6 Myxobacteria: Chemical Diversity and Screening Strategies 103 Alberto Plaza and Rolf M uller 7 Fungal Endophytes of Grasses and Morning Glories, and Their Bioprotective Alkaloids 125 Christopher L. Schardl, Li Chen, and Carolyn A. Young 8 Fungal-Actinomycete Interactions -Wakening of Silent Fungal Secondary Metabolism Gene Clusters via Interorganismic Interactions 147 Volker Schroeckh, Hans-Wilhelm N utzmann, and Axel A. Brakhage 9 Secondary Metabolites Produced by Plant Pathogens 159 Barbara J. Howlett SECTION II FROM GENES TO MOLECULES 171 Part 1 Reading the Genome 173 10 Analyzing Fungal Secondary Metabolite Genes and Gene Clusters 175 Yi-Ming Chiang, Clay C. C. Wang, and Berl R. Oakley Part 2 Biosynthesis and Heterologous Expression 195 11 RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptides 197 Noah A. Bindman and Wilfred A. Van Der Donk 12 Polyketide Synthase: Sequence, Structure, and Function 219 Joel Bruegger, Grace Caldara, Joris Beld, Michael D. Burkart, and Shiou-Chuan (Sheryl) Tsai 13 Manipulation of Fungal Natural Product Pathways 245 Russell J. Cox and Katherine Williams 14 Production of Therapeutic Products 261 Guojian Zhang and Blaine A. Pfeifer Part 3 Regulation: Waking Sleeping Pathways 277 15 Waking Sleeping Pathways in Filamentous Fungi 279 Joe Spraker and Nancy Keller SECTION III EVOLVING ENZYMES, EVOLVING PATHWAYS: SYNTHETIC BIOLOGY 293 Part 1 Chemical Diversification 295 16 The Oxidosqualene Cyclases: One Substrate, Diverse Products 297 Ikuro Abe 17 Harnessing Sugar Biosynthesis and Glycosylation to Redesign Natural Products and to Increase Structural Diversity 317 Carlos Olano, Carmen M endez, and Jos e A. Salas Part 2 Evolving Pathways 341 18 Evolutionary Mechanisms Involved in Development of Fungal Secondary Metabolite Gene Clusters 343 Geromy G. Moore, J er^ome Collemare, Marc-Henri Lebrun, and Rosie E. Bradshaw Part 3 Synthetic Biology 357 19 Synthetic Biology of Natural Products 359 Rainer Breitling and Eriko Takano SECTION IV SCREENING FOR BIOACTIVITY 371 20 Image-Based Screening Approaches to Natural Products Discovery 373 Christopher J. Schulze and Roger G. Linington 21 Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs 397 David J. Newman and Gordon M. Cragg 22 Is There an Ideal Database for Natural Products Research? 413 John W. Blunt and Murray H. G. Munro SECTION V TO APPLICATION 433 Case Studies 435 23 Daptomycin and A54145: Structure-Activity Relationship (SAR) Studies Enabled by Combinatorial Biosynthesis 437 Richard H. Baltz 24 Discovery and Development of NVB302, a Semisynthetic Antibiotic for Treatment of Clostridium difficile Infection 455 Steven Boakes and Michael J. Dawson 25 ILS-920: A Rapamycin Analog for Ischemic Stroke 469 Edmund I. Graziani 26 BC265: A Nonquinone Ansamycin Hsp90 Inhibitor Developed Using Biosynthetic Medicinal Chemistry 483 Matthew A. Gregory, Steven J. Moss, and Barrie Wilkinson 27 Discovery and Development of Caspofungin (CANCIDAS): Concept to Clinic 497 James M. Balkovec, David L. Hughes, Prakash S. Masurekar, Carole A. Sable, Robert E. Schwartz, and Sheo B. Singh Index 523
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