Natural Products

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.

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
Paweł 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 Quévrain, 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 Müller

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 Nützmann, 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 Mndez, and José A. Salas

Part 2 Evolving Pathways 341

18 Evolutionary Mechanisms Involved in Development of Fungal Secondary Metabolite Gene Clusters 343
Geromy G. Moore, Jérôme 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