The editorsAnne 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.

• SECTION I NATURAL PRODUCTS IN THE NATURAL WORLD 1Part 1 Role and Reason 31 The Role of Phytochemicals in Relationships of Plants with Other Organisms 5Paweł Bednarek2 Designer Microbial Ecosystems – Toward Biosynthesis with Engineered Microbial Consortia 23David M. Babson, Mark Held, and Claudia Schmidt-Dannert3 Marine Natural Products – Chemical Defense/Chemical Communication in Sponges and Corals 39Elodie Quévrain, Isabelle Domart-Coulon, and Marie-Lise Bourguet-KondrackiPart 2 Self-Protection – Avoiding Autotoxicity 674 How Plants Avoid the Toxicity of Self-Produced Defense Bioactive Compounds 69Supaart Sirikantaramas, Mami Yamazaki, and Kazuki SaitoPart 3 Fishing and Pharming 835 Marine Bioprospecting 85Amanda M. Fenner and William H. Gerwick6 Myxobacteria: Chemical Diversity and Screening Strategies 103Alberto Plaza and Rolf Müller7 Fungal Endophytes of Grasses and Morning Glories, and their Bioprotective Alkaloids 125Christopher L. Schardl, Li Chen, and Carolyn A. Young8 Fungal-Actinomycete Interactions –Wakening of Silent Fungal Secondary Metabolism Gene Clusters via Interorganismic Interactions 147Volker Schroeckh, Hans-Wilhelm Nützmann, and Axel A. Brakhage9 Secondary Metabolites Produced by Plant Pathogens 159Barbara J. HowlettSECTION II FROM GENES TO MOLECULES 171Part 1 Reading the Genome 17310 Analyzing Fungal Secondary Metabolite Genes and Gene Clusters 175Yi-Ming Chiang, Clay C. C. Wang, and Berl R. OakleyPart 2 Biosynthesis and Heterologous Expression 19511 RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptides 197Noah A. Bindman and Wilfred A. Van Der Donk12 Polyketide Synthase: Sequence, Structure, and Function 219Joel Bruegger, Grace Caldara, Joris Beld, Michael D. Burkart and Shiou-Chuan (Sheryl) Tsai13 Manipulation of Fungal Natural Product Pathways 245Russell J. Cox and Katherine Williams14 Production of Therapeutic Products 261Guojian Zhang and Blaine A. PfeiferPart 3 Regulation: Waking Sleeping Pathways 27715 Waking Sleeping Pathways in Filamentous Fungi 279Joe Spraker and Nancy KellerSECTION III EVOLVING ENZYMES, EVOLVING PATHWAYS: SYNTHETIC BIOLOGY 293Part 1 Chemical Diversification 29516 The Oxidosqualene Cyclases: One Substrate, Diverse Products 297Ikuro Abe17 Harnessing Sugar Biosynthesis and Glycosylation to Redesign Natural Products and to Increase Structural Diversity 317Carlos Olano, Carmen Mndez, and José A. SalasPart 2 Evolving Pathways 34118 Evolutionary Mechanisms Involved in Development of Fungal Secondary Metabolite Gene Clusters 343Geromy G. Moore, Jérôme Collemare, Marc-Henri Lebrun, and Rosie E. BradshawPart 3 Synthetic Biology 35719 Synthetic Biology of Natural Products 359Rainer Breitling and Eriko TakanoSECTION IV SCREENING FOR BIOACTIVITY 37120 Image-Based Screening Approaches to Natural Products Discovery 373Christopher J. Schulze and Roger G. Linington21 Making Sense of Structures by Utilizing Mother Nature’s Chemical Libraries as Leads to Potential Drugs 397David J. Newman and Gordon M. Cragg22 Is There an Ideal Database for Natural Products Research? 413John W. Blunt and Murray H. G. MunroSECTION V TO APPLICATION 433Case Studies 43523 Daptomycin and A54145: Structure–Activity Relationship (SAR) Studies Enabled by Combinatorial Biosynthesis 437Richard H. Baltz24 Discovery and Development of NVB302, a Semisynthetic Antibiotic for Treatment of Clostridium difficile Infection 455Steven Boakes and Michael J. Dawson25 ILS-920: A Rapamycin Analog for Ischemic Stroke 469Edmund I. Graziani26 BC265: A Nonquinone Ansamycin Hsp90 Inhibitor Developed Using Biosynthetic Medicinal Chemistry 483Matthew A. Gregory, Steven J. Moss, and Barrie Wilkinson27 Discovery and Development of Caspofungin (CANCIDAS): Concept to Clinic 497James M. Balkovec, David L. Hughes, Prakash S. Masurekar, Carole A. Sable, Robert E. Schwartz, and Sheo B. SinghIndex 523

The editorsAnne 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.

• SECTION I NATURAL PRODUCTS IN THE NATURAL WORLD 1Part 1 Role and Reason 31 The Role of Phytochemicals in Relationships of Plants with Other Organisms 5Paweł Bednarek2 Designer Microbial Ecosystems – Toward Biosynthesis with Engineered Microbial Consortia 23David M. Babson, Mark Held, and Claudia Schmidt-Dannert3 Marine Natural Products – Chemical Defense/Chemical Communication in Sponges and Corals 39Elodie Quévrain, Isabelle Domart-Coulon, and Marie-Lise Bourguet-KondrackiPart 2 Self-Protection – Avoiding Autotoxicity 674 How Plants Avoid the Toxicity of Self-Produced Defense Bioactive Compounds 69Supaart Sirikantaramas, Mami Yamazaki, and Kazuki SaitoPart 3 Fishing and Pharming 835 Marine Bioprospecting 85Amanda M. Fenner and William H. Gerwick6 Myxobacteria: Chemical Diversity and Screening Strategies 103Alberto Plaza and Rolf Müller7 Fungal Endophytes of Grasses and Morning Glories, and their Bioprotective Alkaloids 125Christopher L. Schardl, Li Chen, and Carolyn A. Young8 Fungal-Actinomycete Interactions –Wakening of Silent Fungal Secondary Metabolism Gene Clusters via Interorganismic Interactions 147Volker Schroeckh, Hans-Wilhelm Nützmann, and Axel A. Brakhage9 Secondary Metabolites Produced by Plant Pathogens 159Barbara J. HowlettSECTION II FROM GENES TO MOLECULES 171Part 1 Reading the Genome 17310 Analyzing Fungal Secondary Metabolite Genes and Gene Clusters 175Yi-Ming Chiang, Clay C. C. Wang, and Berl R. OakleyPart 2 Biosynthesis and Heterologous Expression 19511 RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptides 197Noah A. Bindman and Wilfred A. Van Der Donk12 Polyketide Synthase: Sequence, Structure, and Function 219Joel Bruegger, Grace Caldara, Joris Beld, Michael D. Burkart and Shiou-Chuan (Sheryl) Tsai13 Manipulation of Fungal Natural Product Pathways 245Russell J. Cox and Katherine Williams14 Production of Therapeutic Products 261Guojian Zhang and Blaine A. PfeiferPart 3 Regulation: Waking Sleeping Pathways 27715 Waking Sleeping Pathways in Filamentous Fungi 279Joe Spraker and Nancy KellerSECTION III EVOLVING ENZYMES, EVOLVING PATHWAYS: SYNTHETIC BIOLOGY 293Part 1 Chemical Diversification 29516 The Oxidosqualene Cyclases: One Substrate, Diverse Products 297Ikuro Abe17 Harnessing Sugar Biosynthesis and Glycosylation to Redesign Natural Products and to Increase Structural Diversity 317Carlos Olano, Carmen Mndez, and José A. SalasPart 2 Evolving Pathways 34118 Evolutionary Mechanisms Involved in Development of Fungal Secondary Metabolite Gene Clusters 343Geromy G. Moore, Jérôme Collemare, Marc-Henri Lebrun, and Rosie E. BradshawPart 3 Synthetic Biology 35719 Synthetic Biology of Natural Products 359Rainer Breitling and Eriko TakanoSECTION IV SCREENING FOR BIOACTIVITY 37120 Image-Based Screening Approaches to Natural Products Discovery 373Christopher J. Schulze and Roger G. Linington21 Making Sense of Structures by Utilizing Mother Nature’s Chemical Libraries as Leads to Potential Drugs 397David J. Newman and Gordon M. Cragg22 Is There an Ideal Database for Natural Products Research? 413John W. Blunt and Murray H. G. MunroSECTION V TO APPLICATION 433Case Studies 43523 Daptomycin and A54145: Structure–Activity Relationship (SAR) Studies Enabled by Combinatorial Biosynthesis 437Richard H. Baltz24 Discovery and Development of NVB302, a Semisynthetic Antibiotic for Treatment of Clostridium difficile Infection 455Steven Boakes and Michael J. Dawson25 ILS-920: A Rapamycin Analog for Ischemic Stroke 469Edmund I. Graziani26 BC265: A Nonquinone Ansamycin Hsp90 Inhibitor Developed Using Biosynthetic Medicinal Chemistry 483Matthew A. Gregory, Steven J. Moss, and Barrie Wilkinson27 Discovery and Development of Caspofungin (CANCIDAS): Concept to Clinic 497James M. Balkovec, David L. Hughes, Prakash S. Masurekar, Carole A. Sable, Robert E. Schwartz, and Sheo B. SinghIndex 523