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.

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 1 – NATURAL PRODUCTS IN THE NATURAL WORLD

Role and reason

1) The role of small molecules in interactions between plants and other organisms (genetic modification in combination with chemical ecology).

- Ian Baldwin, Institute for Chemical Ecology, Jena.

2) What are natural products doing in nature? - A chemistry-based approach.

– Jon Clardy, Harvard Medical School.

3) Modes of action in nature and as chemicals that are exploited by humans (e.g. as antibiotics, anti-cancer agents, immunosuppressants, drugs, insecticides, drugs, herbicides).

- Chris Walsh, Harvard; Michael Thomas, University of Wisconsin.

4) Quorum sensing in bacteria.

– George Salmond, University of Cambridge; Claudia Schmidt-Dannert, University of Minnesota; Rich Losick, Harvard; Miguel Camara, University of Nottingham; Steve Lindow, Oregon State.

5) Antibiotics in nature

– Julian Davies, University of British Columbia.

6) Marine natural products – Chemical defenses/chemical communication in aquatic environments

- Joe Pawlik, University of North Carolina; Julia Kubanek, University of British Columbia; Ute Hentschel, University of Würzburg, Germany.

7) Bryostatins in Bugula neritina (microbial products harnessed as defence compounds by an invertebrate)

- Margo Haygood, Oregon Health & Sciences University

8) Natural products in the gut

- Johanna Lampe, University of Washington; Jens Nielsen, Chalmers University of Technology, Sweden.

9) Metagenomics

- Jorgen Piel

Self-protection – Avoiding autotoxicity

How do organisms that produce bioactives protect themselves, and how can this knowledge be exploited for investigation of mode of action and for predicting drug resistance?

10) Bacteria

- Eric Cundliffe, University of Leicester; Jo Handelsman, Yale.

11) Fungi

- Sean Doyle, National University of Ireland;

12) Plants

– Kazuki Saito, RIKEN, Yokohama, Japan (e.g. camptothecin resistance in plants); Enrico Martinaioa, University of Zurich (transporters); Rob Edwards, University of York (glycosylation and other safening mechanisms).

Fishing and pharming

Current endeavours in the search for new bioactive natural products.

13) Marine bioprospecting

–Bill Gerwick/ Bill Fenical (Scaggs/Scripps, San Diego, UCSD, US).

14) Soil bacteria/myxobacteria

– Sean Brady, Rockefeller University; Rolf Muller, Saarland University, Germany.

15) Endophytic fungi

–Gary Strobel, Montana State University; Chris Schardl, University of Kentucky.

16) Tropical reef symbioses. Metagenomic (environmental genomic) approaches to understand the evolution and diversity of natural product pathways; engineering production of small molecule libraries for the treatment of human diseases.

– Erich Schmidt, University of Utah.

17) Actinomycete interactions – waking up pathways via inter-organismal interactions.

– Matt Hutchings, University of East Anglia, UK; Michael Fischbach, UCSF; Peter Dorrestein, Scaggs/Scripps, San Diego, UCSD, US.

18) Plant pathogens and basidiomycetes.

– Jon Walton, Michigan State.

19) Mining plant metabolic diversity

- Monique Simmons, Kew Gardens, London.

SECTION 2 – FROM GENES TO MOLECULES

Reading the genome

20) Actinomycetes

– Michael Fishbach, Univerity of California, San Francisco; Greg Challis, University of Warwick, UK;

21) Filamentous fungi

- Berl Oakley, University of Kanses; Dirk Hoffmeister, Leibniz Institute, Jena, Germany; Robert Cichewicz, University of Oklahoma.

22) Plants

- Seiichi Matsuda, Rice University, Texas (the triterpene complement of Arabidopsis); Jörg Bohlmann, University of British Columbia (the terpenome); Robin Buell, Michigan State (medicinal plant genomics).

Biosynthesis and heterologous expression

23) Polyketide synthases

- Brad Moore, Scaggs/Scripps, San Diego; Ben Shen, University of Wisconsin; David Sherman, University of Michigan; Taifo Mahmud, Oregon State.

24) Non-ribosomal peptide synthases

- Chris Walsh (Harvard); Mohamed Marahiel (University of Marburg, Germany); Wilfred van der Donk (University of Illinois)

25) Sequence, structure, function

- Sheryl Tsai, University of California (actinomycetes, multi-domain complexes, structural biology)

26) Cluster cross-talk

- Peter Leadlay, University of Cambridge, UK; Susan Jensen, University of Alberta;

Kira Weissman, University of Nancy.

27) Manipulation of fungal natural product pathways

- Russell Cox, Tony Simpson, Colin Lazarus, University of Bristol, UK

28) Production of therapeutic products

- Blaine Pfeifer, Tufts University, US.

29) Plant expression systems

- Cathie Martin, George Lomonossoff, John Innes Centre, Norwich, UK.

Regulation - waking sleeping pathways

30) Microbes

– Mervyn Bibb/Michael McArthur (John Innes Centre, Norwich, UK)

31) Filamentous fungi

– Nancy Keller, University of Wisconsin, Madison; Axel Brakhage, Jena; Barbara Howlett, Melbourne.

32) Plants

–Erich Grotewold, Ohio State University.

33) Chemical biology

– Stuart Schreiber, Harvard

SECTION 3 – EVOLVING ENZYMES, EVOLVING PATHWAYS: SYNTHETIC BIOLOGY

Chemical diversification

34) The oxidosqualene cyclases: One substrate, diverse products.

- Ikuro Abe, University of Shizuoka, Japan.

35) Sugar decorations

– Jon Thorson, University of Wisconsin; Ben Davies, University of Oxford; Jurgen Rohr, University of Kentucky.

36) Traversing the catalytic landscape

- Joe Noel, Salk Institute, San Diego; Paul O’Maille, John Innes Centre, Norwich, UK.

Evolving pathways

37) Recombination and gene loss in fungal gene clusters

- Ignacio Carbone

38) Synthesis of molecules and molecular assemblies with novel physical, chemical or biological properties and functions; expanding the genetic code

– Peter Schulz, Floyd Romesberg (Scripps)

39) Directed evolution

- Jay Keasling, UC Berkeley

Synthetic biology

40) Exploiting tools from microbes and plants for synthesis of novel natural products

– Sarah O’Conner, John Innes Centre, Norwich, UK.

41) Synthetic biology for drug discovery

- Eriko Takano, University of Groningen, the Netherlands.

SECTION 4 – SCREENING FOR BIOACTIVITY

42) Screens for novel bioactives

– Fred Ausubel (Harvard)

43) Making sense of structures

– David Newman, National Cancer Institute

44) Structures, databases, bioactivity

– John Blunt, University of Canterbury, New Zealand

45) Natural product screening

- Satoshi Omura, Kitasato Institute in Tokyo, Japan; Frank Petersen, Novartis.

SECTION 5 - TO APPLICATION

46) Synthetic problems and clinical opportunities

- Paul Wender, Stanford

47) Case studies

Introduction

- Mike Ward, Scripps Intelligence

Several case studies (depending on availability of authors) which could include examples from the following:

Saliosporamide (Bill Fenical, Scaggs/Scripps, San Diego)

Curare

Biotica (Barrie Wilkinson)

Novacta (Mike Dawson)

Cubist (Richard Baltz)

PharmaMar

GeneBridges (Youmin Zhang)

Caspofungin - Merck (Sheo Singh)

FTY-720 Novartis

Aquapharm

What is included with this book?

The New copy of this book will include any supplemental materials advertised. Please check the title of the book to determine if it should include any access cards, study guides, lab manuals, CDs, etc.

The Used, Rental and eBook copies of this book are not guaranteed to include any supplemental materials. Typically, only the book itself is included. This is true even if the title states it includes any access cards, study guides, lab manuals, CDs, etc.