CONTENTS

Cover

Related Titles

Title Page

List of Contributors

Foreword

Preface

Part One: Outstanding Marine Molecules from a Chemical Point of View

Chapter 1: Marine Cyanotoxins Potentially Harmful to Human Health
1. 1.1 Introduction
2. 1.2 Marine Cyanobacteria as Causative Agent of Ciguatera-Like Poisoning
3. 1.3 Marine Cyanobacteria: A Potential Risk for Swimmers
4. 1.4 Microcystins Could also be Found in the Sea
5. 1.5 Risk of Neurodegenerative Disease in the Sea
6. 1.6 Conclusion and Future Prospects
7. Acknowledgments
8. References
Chapter 2: Outstanding Marine Biotoxins: STX, TTX, and CTX
1. 2.1 Introduction
2. 2.2 Saxitoxins (STXs) in Paralytic Shellfish Poisoning
3. 2.3 Tetrodotoxin (TTX) in Puffer Fish Poisoning (PFP)
4. 2.4 Ciguatoxin (CTX) in Ciguatera Fish Poisoning (CFP)
5. 2.5 Conclusions
6. References
Chapter 3: Impact of Marine-Derived Penicillium Species in the Discovery of New Potential Antitumor Drugs
1. 3.1 Introduction
2. 3.2 Molecules Isolated from Marine-Derived Penicillium Species With Potent Cytotoxic Activity
3. 3.3 Marine-Derived Cytotoxic Penicillium
4. 3.4 What are these Promising Molecules from Marine Penicillium?
5. 3.5 Conclusions
6. References
Chapter 4: Astonishing Fungal Diversity in Deep-Sea Hydrothermal Ecosystems: An Untapped Resource of Biotechnological Potential?
1. 4.1 Introduction
2. 4.2 Deep-Sea Hydrothermal Vents as Life Habitats
3. 4.3 The Five “W”s of Marine fungi: Who? What? When? Where? Why?
4. 4.4 Fungi in Deep-Sea Hydrothermal Vents
5. 4.5 Conclusions
6. Acknowledgments
7. References
Chapter 5: Glycolipids from Marine Invertebrates
1. 5.1 Introduction
2. 5.2 Glycosphingolipids from Marine Invertebrates: Occurrence, Characterization, and Biological Activity
3. 5.3 Gangliosides
4. 5.4 Atypical Glycolipids
5. 5.5 General Conclusion
6. List of Abbreviations
7. References
Chapter 6: Pigments of Living Fossil Crinoids
1. 6.1 The Discovery of Stalked Crinoids
2. 6.2 Anthraquinonic Pigments of Stalked Crinoids
3. 6.3 Axial Chirality of Gymnochromes and Hypochromines
4. 6.4 Towards a Fungal Origin of Gymnochromes?
5. 6.5 Biological Activities of Gymnochromes
6. 6.6 Perspectives
7. References

Part Two: Outstanding Marine Molecules from an Ecological Point of View

Chapter 7: Bacterial Communication Systems
1. 7.1 Coordination of Multicellular Behavior in Bacteria
2. 7.2 The Repertoire of Chemical Signals
3. 7.3 Molecular Mechanisms of QS
4. 7.4 The Effective Range of QS-Regulated Processes
5. 7.5 The Inhibition of QS: Quorum Quenching
6. 7.6 Examples of Cross-Kingdom Signaling in the Marine Environment
7. 7.7 “-Omic” Approaches to QS
8. 7.8 Concluding Remarks
9. References
Chapter 8: Domoic Acid
1. 8.1 Historical Background
2. 8.2 Case Studies
3. 8.3 Chemistry
4. 8.4 DA-Producing Organisms
5. 8.5 Molecular Basis of DA Acute and Chronic Poisoning
6. 8.6 Understanding and Predicting Toxigenic Diatom Blooms (Macroscopic Scale)
7. 8.7 Natural Factors that Enhance Bloom Formation and/or DA Production
8. 8.8 Functional Genomics of Diatoms
9. 8.9 Conclusions
10. Note added in proof
11. Acknowledgments
12. References
Chapter 9: Algal Morpho-Inducers
1. 9.1 Introduction
2. 9.2 Morpho-Inducers of Animals and Land Plants Produced by Macroalgae
3. 9.3 Morpho-Inducers of Macroalgae
4. 9.4 Conclusions
5. Acknowledgment
6. References
Chapter 10: Halogenation and Vanadium Haloperoxidases
1. 10.1 Introduction
2. 10.2 Biochemical Characterization of Vanadium-Dependent Haloperoxidases (VHPOs)
3. 10.3 Structural Characterization of VHPOs
4. 10.4 Catalytic Cycle and Halide Specificity
5. References

Part Three: Outstanding Marine Molecules with Particular Biological Activities Outstanding

Chapter 11: Promising Marine Molecules in Pharmacology
1. 11.1 Introduction
2. 11.2 Promising Substances Isolated from Microorganisms
3. 11.3 Promising Substances Isolated from Macroalgae and Invertebrates
4. 11.4 Promising Substances Synthesized from Natural Models
5. 11.5 Conclusion
6. References
Chapter 12: Promises of the Unprecedented Aminosterol Squalamine
1. 12.1 Introduction
2. 12.2 Discovery of the Unprecedented Aminosterol Squalamine
3. 12.3 Syntheses of Squalamine
4. 12.4 Biological Activities
5. 12.5 Mechanism of Antiangiogenic Activity of Squalamine
6. 12.6 Preclinical Studies of Squalamine
7. 12.7 Clinical Studies of Squalamine
8. 12.8 Bioactive Potential of Trodusquemine, a Natural Squalamine Derivative
9. 12.9 Conclusion
10. References
Chapter 13: Marine Peptide Secondary Metabolites
1. 13.1 Introduction
2. 13.2 Ribosomal- and Nonribosomal-Derived Peptides: A Virtually Unlimited Source of New Active Compounds
3. 13.3 Laxaphycins and their Derivatives: Peptides Not So Easy to Synthesize
4. 13.4 Dolastatins: From Deception to Hope Through Structural Modification Leading to Reduced Toxicity
5. 13.5 Didemnins and Related Depsipeptides: How Perseverance Should Lead to Their Low-Cost Production
6. 13.6 Kahalalide F: A Study in Chemical Ecology as a Starting Point for New Antitumoral Agent Discovery
7. 13.7 Azole/Azoline-Containing Cyanobactins Isolated from Invertebrates: An Example of Nature's Own Combinatorial Chemistry
8. 13.8 Conclusion
9. Acknowledgments
10. References
Chapter 14: Conotoxins and Other Conopeptides
1. 14.1 Background
2. 14.2 Diversity of Conopeptides
3. 14.3 Isolation Techniques
4. 14.4 Conopeptide Three-Dimensional Structures
5. 14.5 Conopeptide Pharmacological Activities
6. 14.6 Outlook
7. Acknowledgments
8. Notes
9. References
Chapter 15: Mycosporine-Like Amino Acids (MAAs) in Biological Photosystems
1. 15.1 Background
2. 15.2 Chemistry
3. 15.3 MAA-Producing Organisms
4. 15.4 Hermatypic Corals: Living Under Tight Constraints
5. 15.5 Lichenic Systems: Living in the Extremes
6. 15.6 Modes of Action and Applications to Human Welfare
7. 15.7 Conclusions
8. Acknowledgments
9. 15.A
10. Appendix 15A.1 Precursors and degradation products
11. Appendix 15A.2 Carbon thirteen data of Mycosporines and Mycosporine-like Amino Acids
12. References
Chapter 16: Extracellular Hemoglobins from Annelids, and their Potential Use in Biotechnology
1. 16.1 Introduction
2. 16.2 Annelid Extracellular Hemoglobins
3. 16.3 Architecture
4. 16.4 Model of Quaternary Structures
5. 16.5 Biotechnology Applications
6. 16.6 Organ Preservation
7. 16.7 Anemia
8. 16.8 Conclusion
9. Acknowledgments
10. References
Chapter 17: Lamellarins: A Tribe of Bioactive Marine Natural Products
1. 17.1 Introduction
2. 17.2 Lamellarins: Bioactive Marine Natural Products
3. 17.3 Anticancer Activities of Lamellarins
4. 17.4 Inhibition of Topoisomerase I by Lamellarins
5. 17.5 Inhibition of Protein Kinases by Lamellarins
6. 17.6 Lamellarin-induced Mitochondrial Perturbations
7. 17.7 Antiviral Activity of Sulfated Lamellarins
8. 17.8 Synthesis of Lamellarins
9. 17.9 Non-Natural Lamellarin Analogs
10. 17.10 Conclusion
11. References

Part Four: New Trends in Analytical Methods

Chapter 18: NMR to Elucidate Structures
1. 18.1 Introduction
2. 18.2 NMR to Elucidate Structures
3. 18.3 Sample Preparation
4. 18.4 Conventional “Liquid” Probes: Obtaining 1D and 2D Spectra of all NMR-Observable Nuclei
5. 18.5 Cryoprobes: Obtaining 1D and 2D Spectra Mainly in ¹H1, ¹³C
6. 18.6 HRMASNMR: Obtaining 1H, 13C, 31P, 15N 1D and 2D Spectra
7. 18.7 CPMASNMR: Obtaining all NMR Observable Nuclei Spectra
8. 18.8 Conclusion
9. References
Chapter 19: An Introduction to Omics
1. 19.1 What are “Omics”?
2. Notes
3. References
Chapter 20: Gene Mining for Environmental Studies and Applications: Examples from Marine Organisms
1. 20.1 Introduction
2. 20.2 Techniques
3. 20.3 Current Applications
4. 20.4 Conclusions and Outlook
5. References
Chapter 21: Proteomics and Metabolomics of Marine Organisms: Current Strategies and Knowledge
1. 21.1 Introduction
2. 21.2 General Strategies for Proteomics and Peculiarities of the Marine Environment
3. 21.3 General Strategies for Metabolomics, and Peculiarities of the Marine Environment
4. 21.4 Conclusions
5. Acknowledgments
6. References
Chapter 22: Genomics of the Biosynthesis of Natural Products: From Genes to Metabolites
1. 22.1 Introduction
2. 22.2 Biosynthesis of PKs, NRPs and RiPPs: Basic Principles
3. 22.3 Connecting Genes and Metabolites: Selected Examples of Aquatic Natural Product Biosynthesis
4. 22.4 Conclusions and Perspectives
5. Abbreviations
6. References
Chapter 23: High-Throughput Screening of Marine Resources
1. 23.1 Introduction
2. 23.2 High-Throughput Screening and Drug Development
3. 23.3 Examples of High-Throughput Screening
4. 23.4 Conclusions and Perspectives
5. List of Abbreviations
6. Acknowledgments
7. References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 2.6

Table 2.7

Table 2.8

Table 2.9

Table 3.1

Table 3.2

Table 3.3

Table 3.4

Table 3.5

Table 3.6

Table 3.7

Table 5.1

Table 5.2

Table 5.3

Table 5.4

Table 5.5

Table 5.6

Table 5.7

Table 5.8

Table 5.9

Table 5.10

Table 5.11

Table 5.12

Table 5.13

Table 5.14

Table 5.15

Table 5.16

Table 5.17

Table 5.18

Table 5.19

Table 5.20

Table 5.21

Table 7.1

Table 8.1

Table 8.2

Table 10.1

Table 10.2

Table 10.3

Table 11.1

Table 11.2

Table 11.3

Table 12.1

Table 13.1

Table 13.2

Table 14.1

Table 14.2

Table 16.1

Table 16.2

Table 16.3

Table 16.4

Table 18.1

Table 18.2

Table 18.3

Table 18.4

Table 18.5

Table 18.6

Table 18.7

Table 18.8

Table 18.9

Table 19.1

Table 20.1

Table 20.2

Table 22.1

Table 23.1

Table 23.2

List of Illustrations

Figure 1.1

Figure 1.2

Figure 1.3

Figure 1.4

Figure 1.5

Figure 1.6

Figure 1.7

Figure 1.8

Figure 1.9

Figure 1.10

Figure 1.11

Figure 1.12

Figure 1.13

Figure 1.14

Figure 1.15

Figure 1.16

Figure 1.17

Figure 1.18

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

Figure 2.8

Figure 2.9

Figure 2.10

Figure 2.11

Figure 2.12

Figure 2.13

Figure 2.14

Figure 2.15

Figure 2.16

Figure 2.17

Figure 3.1

Figure 3.2

Figure 3.3

Figure 3.4

Figure 3.5

Figure 3.6

Figure 3.7

Figure 3.8

Figure 3.9

Figure 3.10

Figure 3.11

Figure 3.12

Figure 3.13

Figure 3.14

Figure 3.15

Figure 3.16

Figure 3.17

Figure 4.1

Figure 4.2

Figure 4.3

Figure 4.4

Figure 4.5

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 5.5

Figure 5.6

Figure 5.7

Figure 5.8

Figure 5.9

Figure 5.10

Figure 5.11

Figure 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 6.5

Figure 7.1

Figure 7.2

Figure 7.3

Figure 7.4

Figure 7.5

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Figure 8.5

Figure 8.6

Figure 8.7

Figure 8.8

Figure 8.9

Figure 8.10

Figure 8.11

Figure 8.12

Figure 8.13

Figure 8.14

Figure 8.15

Figure 8.16

Figure 9.1

Figure 9.2

Figure 9.3

Figure 9.4

Figure 10.1

Figure 10.2

Figure 10.3

Figure 10.4

Figure 10.5

Figure 10.6

Figure 10.7

Figure 10.8

Figure 10.9

Figure 10.10

Figure 10.11

Figure 11.1

Figure 11.2

Figure 11.3

Figure 11.4

Figure 11.5

Figure 11.6

Figure 11.7

Figure 11.8

Figure 11.9

Figure 11.10

Figure 11.11

Figure 11.12

Figure 11.13

Figure 11.14

Figure 12.1

Figure 12.2

Figure 12.3

Figure 12.4

Figure 12.5

Scheme 12.1

Scheme 12.2

Scheme 12.3

Scheme 12.4

Scheme 12.5

Scheme 12.6

Scheme 12.7

Figure 12.6

Figure 12.7

Figure 12.8

Figure 12.9

Figure 12.10

Figure 12.11

Figure 13.1

Figure 13.2

Figure 13.3

Figure 13.4

Figure 13.5

Figure 13.6

Figure 13.7

Figure 13.8

Figure 13.9

Figure 13.10

Figure 13.11

Figure 13.12

Figure 13.13

Figure 13.14

Figure 13.15

Figure 13.16

Figure 13.17

Figure 13.18

Figure 13.19

Figure 13.20

Figure 13.21

Figure 13.22

Figure 13.23

Figure 13.24

Figure 14.1

Figure 14.2

Figure 14.3

Figure 14.4

Figure 14.5

Figure 14.6

Figure 15.1

Figure 15.2

Figure 15.3

Figure 15.4

Figure 15.5

Figure 15.6

Figure 15.7

Figure 15.8

Figure 15.9

Figure 15.10

Figure 16.1

Figure 16.2

Figure 16.3

Figure 16.4

Figure 16.5

Figure 16.6

Figure 16.7

Figure 16.8

Figure 16.9

Figure 16.10

Figure 17.1

Figure 17.2

Figure 17.3

Figure 17.4

Figure 17.5

Figure 17.6

Figure 18.1

Figure 18.2

Figure 18.3

Figure 18.4

Figure 18.5

Figure 18.6

Figure 18.7

Figure 18.8

Figure 18.9

Figure 18.10

Figure 18.11

Figure 18.12

Figure 18.13

Figure 18.14

Figure 18.15

Figure 18.16

Figure 18.17

Figure 18.18

Figure 18.19

Figure 18.20

Figure 18.21

Figure 18.22

Figure 18.23

Figure 18.24

Figure 18.25

Figure 18.26

Figure 18.27

Figure 18.28

Figure 18.29

Figure 18.30

Figure 18.31

Figure 18.32

Figure 18.33

Figure 18.34

Figure 18.35

Figure 18.36

Figure 18.37

Figure 18.38

Figure 18.39

Figure 18.40

Figure 18.41

Figure 18.42

Figure 18.43

Figure 18.44

Figure 18.45

Figure 18.46

Figure 18.47

Figure 18.48

Figure 18.49

Figure 18.50

Figure 18.51

Figure 18.52

Figure 18.53

Figure 18.54

Figure 18.55

Figure 18.56

Figure 18.57

Figure 18.58

Figure 18.59

Figure 18.60

Figure 18.61

Figure 18.62

Figure 18.63

Figure 18.64

Figure 18.65

Figure 18.66

Figure 18.67

Figure 18.68

Figure 18.69

Figure 18.70

Figure 18.71

Figure 18.72

Figure 18.73

Figure 18.74

Figure 19.1

Figure 20.1

Figure 20.2

Figure 20.3

Figure 21.1

Figure 21.2

Figure 21.3

Figure 22.1

Figure 22.2

Figure 22.3

Figure 22.4

Figure 22.5

Figure 22.6

Figure 22.7

Figure 22.8

Figure 22.9

Figure 22.10

Figure 22.11

Figure 23.1

Figure 23.2

Figure 23.3

Figure 23.4

Figure 23.5

List of Contributors

Ali Al-Mourabit

Natural Product Chemistry Institute (ICSN)

Department of Natural Products & Medicinal Chemistry (SNCM)

Research Center of the CNRS at Gif sur Yvette

Avenue de la terrasse

91190 Gif sur Yvette

France

Ali.Almourabit@icsn.cnrs-gif.fr

Philippe Amade

Université de Nice Sophia Antipolis

Institut de Chimie de Nice, UMR 7272 CNRS, Faculté des Sciences

Parc Valrose

06108 Nice cedex 2

France

amade@unice.fr

Zouher Amzil

IFREMER (Institut Français de Recherche pour l'Exploitation de la Mer)

Laboratoire Phycotoxines

Rue de l'Ile d'Yeu, BP21105

F-44311 Nantes cedex 3

France

Zouher.Amzil@ifremer.fr

Romulo Aráoz

Institut Fédératif de Neurobiologie Alfred Fessard FR2118,

Center de recherche CNRS de Gif-sur-Yvette, Laboratoire de Neurobiologie et Développement UPR 3294

1 avenue de la Terrasse

91198 Gif sur Yvette Cedex

France

araoz@inaf.cnrs-gif.fr

Stéphane S. Bach

Sorbonne Universités

UPMC Univ Paris 06

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

bach@sb-roscoff.fr

and

CNRS

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Christian Bailly

Institut de Recherche Pierre Fabre

Centre de Recherche et Développement

3 Avenue Hubert Curien - BP 13562

31035 Toulouse Cedex 1

France

christian.bailly@pierre-fabre.com

Bernard Banaigs

Université de Perpignan via Domitia

Laboratoire de chimie des biomolécules et de l'environnement, EA4215

52 avenue Paul Alduy

66860 Perpignan cedex

France

banaigs@univ-perp.fr

Georges Barbier

Université Européenne de Bretagne, Université de Brest, ESMISAB

Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (EA3882)

IFR 148, Technopole Brest-Iroise

29280 Plouzané

France

georges.barbier@univ-brest.fr

Gilles Barnathan

Université de Nantes

Groupe Mer-Molécules-Santé MMS/EA 2160, Équipe CHIM – Lipides marins à activité biologique, Faculté des Sciences pharmaceutiques et biologiques, Institut Universitaire Mer et Littoral FR3473 CNRS

9 rue Bias

BP 53508

44035 Nantes

France

gilles.barnathan@univ-nantes.fr

Stephen S. Bates

Fisheries and Oceans Canada

Gulf Fisheries Centre

P.O. Box 5030

Moncton

New Brunswick

E1C 9B6 Canada

Stephen.Bates@dfo-mpo.gc.ca

Elodie Blanchet

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

Franceand

Atlanthera, Atlantic Bone Screen

F-44800 Saint Herblain

Nantes

France

elodie.blanchet@univ-nantes.fr

Isabelle Bonnard

Université de Perpignan via Domitia

Laboratoire de chimie des biomolécules et de l'environnement, EA4215

52 avenue Paul Alduy

66860 Perpignan cedex

France

isabelle.bonnard@univ-perp.fr

Marie-Lise Bourguet-Kondracki

Muséum National d'Histoire Naturelle

Molécules de Communication et Adaptation des Micro-Organismes (MCAM) UMR 7245 CNRS/MNHN

57 rue Cuvier (CP 54)

75005 Paris

France

bourguet@mnhn.fr

Joël Boustie

Université de Rennes 1

Equipe PNSCM (Produits Naturels, Synthèses et Chimie Médicinale), UMR CNRS

6226, Faculté des Sciences Pharmaceutiques et Biologiques

2 Av. du Pr. Léon Bernard

35043 Rennes Cedex

France

Joel.Boustie@univ-rennes1.fr

Catherine Boyen

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

boyen@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Jean-Michel Brunel

Aix-Marseille Université

Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258; Institut Paoli Calmettes

UM 105; Inserm, U1068

F-13009 Marseille

France

bruneljm@yahoo.fr

Gaëtan Burgaud

Université Européenne de Bretagne, Université de Brest, ESMISAB

Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (EA3882)

IFR 148, Technopole Brest-Iroise

29280 Plouzané

France

gaetan.burgaud@univ-brest.fr

Alyssa Carré-Mlouka

National Museum of Natural History

75005 Paris

France

alyssa.carre@mnhn.fr

Stéphane Cérantola

Université de Bretagne Occidentale

Technological Platform of Nuclear Magnetic Resonance, Electron Paramagnetic Resonance and Mass Spectrometry

6, av. Victor Le Gorgeu, CS93837

29238 Brest Cedex 3

France

stephane.cerantola@univ-brest.fr

Bénédicte Charrier

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francecharrier@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Mireille Chinain

Institut Louis Malardé

Laboratoire de recherche sur les Microalgues Toxiques

BP30, 98713 Papeete

Tahiti

French Polynesia

mchinain@ilm.pf

Jonas Collén

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francecollen@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Aurélie Couzinet-Mossion

Université de Nantes

9 rue Bias

BP 53508

44035 Nantes

France

aurelie.couzinet-mossion@univ-nantes.fr

David J. Craik

The University of Queensland

Institute for Molecular Bioscience

Brisbane

QLD 4072

Australia

d.craik@imb.uq.edu.au

Cécile Debitus

Institut de Recherche pour le Développement

UMR 241

BP 529, 98713 Papeete

Polynésie Française

cecile.debitus@ird.fr

Simon M. Dittami

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francedittami@sb-roscoff.fr

Sergey Dobretsov

Sultan Qaboos University

P. O. Box 50

Muscat 123

Oman

sergey@squ.edu.om

Virginia. P. Edgcomb

Woods Hole Oceanographic Institution

Geology and Geophysics Department

Woods Hole

MA 02543

USA

vedgcomb@whoi.edu

Jean-Baptiste Fournier

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francejbfournier@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Fanny Gaillard

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francegaillard@sb-roscoff.fr

Stjepko Golubic

Boston University

Biological Science Center

5 Cummington Street

Boston

MA 02215

USA

golubic@bu.edu

Olivier Grovel

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

olivier.grovel@univ-nantes.fr

Muriel Gugger

Institut Pasteur, Collection des Cyanobacteéries

Dé??partement de Microbiologie

28 rue du Dr Roux

75015 Paris

France

muriel.gugger@pasteur.fr

Yann Guitton

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

Yann.Guitton@univ-nantes.fr

Tilmann Harder

University of New South Wales

Centre for Marine Bio-Innovation, School of Biological, Earth and Environmental Science

Sydney

Australia 2052

t.harder@unsw.edu.au

Arnaud Hochard

USR3151-CNRS

Protein phosphorylation and human diseases, Kinase Inhibitor Specialized Screening facility (KISSf)

Station Biologique CNRS-UPMC

Place Georges Teissier, CS 90074

29688 Roscoff

Bretagne

France

hochard.arnaud@orange.fr

Nicolas Inguimbert

Université de Perpignan via Domitia

Laboratoire de chimie des biomolécules et de l'environnement, EA4215

52 avenue Paul Alduy

66860 Perpignan cedex

France

nicolas.inguimbert@univ-perp.fr

Quentin Kaas

The University of Queensland

Institute for Molecular Bioscience

Brisbane

QLD 4072

Australia

q.kaas@imb.uq.edu.au

Nelly Kervarec

Université de Bretagne Occidentale

Technological Platform of Nuclear Magnetic Resonance, Electron Paramagnetic Resonance and Mass Spectrometry

6, av. Victor Le Gorgeu, CS93837

29238 Brest Cedex 3

France

nelly.kervarec@univ-brest.fr

Staffan Kjellberg

University of New South Wales

Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Science

Sydney

Australia 2052

and

Nanyang Technological University

Singapore Centre on Environmental Life Sciences Engineering

Singapore 639798

s.kjellberg@unsw.edu.au

Jean-Michel Kornprobst (Editor)

Institut Mer et Littoral

Bâtiment Isomer2, rue de la Houssiniére

44322 Nantes BP 92208 Cedex 3France

jean-michel.kornprobst@univ-nantes.fr

Stéphane La Barre (Editor)

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francelabarre@sb-roscoff.fr

Dominique Laurent

Institut de Recherche pour le Développement (IRD)

Pharma-Dev UMR 152

BP529, 98713 Papeete

Tahiti

French Polynesia

domnique.laurent@ird.fr

Catherine Leblanc

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Franceleblanc@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Richard J. Lewis

University of Queensland

Institute for Molecular Bioscience

306, Carmody Road

St Lucia

QLD 4072

Australia

r.lewis@imb.uq.edu.au

Diane McDougald

University of New South Wales

Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Science

Sydney

Australia 2052

and

Nanyang Technological University

Advanced Environmental Biotechnology Centre, Nanyang Environment and Water Institute

Singapore 639798

d.mcdougald@unsw.edu.au

Mohamed Mehiri

Université de Nice Sophia Antipolis

Institut de Chimie de Nice, UMR 7272 CNRS, Faculté des Sciences

Parc Valrose

06108 Nice cedex 2

France

mohamed.mehiri@unice.fr

Annick Méjean

Chimie ParisTech, ENSCP

Laboratoire Charles Friedel

11 rue Pierre et Marie Curie

75231 Paris Cedex 05

France

and

CNRS, UMR 7223

11 rue Pierre et Marie Curie

75231 Paris Cedex 05

France

and

Université Paris Diderot

35 rue Hélène Brion

75205 Paris Cedex 13

France

annick-mejean@chimie-paristech.fr

Laurence Meslet-Cladière

Université Européenne de Bretagne, Université de Brest, ESMISAB

Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (EA3882)

IFR 148, Technopole Brest-Iroise

29280 Plouzané

France

laurence.meslet-cladiere@sb-roscoff.fr

Zofia Nehr

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Franceznehr@sb-roscoff.fr

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Olivier Ploux

Chimie ParisTech, ENSCP

Laboratoire Charles Friedel

11 rue Pierre et Marie Curie

75231 Paris Cedex 05

France

and

CNRS, UMR 7223

11 rue Pierre et Marie Curie

75231 Paris Cedex 05

France

olivier-ploux@chimie-paristech.fr

Philippe Potin

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francepotin@sb-roscoff.fr

Yves-François Pouchus

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

yves-francois.pouchus@univ-nantes.fr

Michael Quilliam

National Research Council Canada

Measurement Science and Standards

1411 Oxford Street

Halifax

Nova Scotia

B3 H 3Z1 Canada

michael.quilliam@nrc-cnrc.gc.ca

Luc Reininger

Sorbonne Universités

UPMC Univ Paris 06

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Franceluc.reininger@sb-roscoff.fr

and

CNRS

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Scott A. Rice

University of New South Wales

Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Science

Sydney

Australia 2052

and

Nanyang Technological University

Singapore Centre on Environmental Life Sciences Engineering

Singapore 639798

Scott.Rice@unsw.edu.au

Mélanie Roué

Research ScientistIRD-UMR 241 (EIO)Centre Polynésien de Recherche et de valorisation de la Biodiversité Insulaire

B.P. 529, 98713 Papeete, Polynésie Française

melanie.roue@ird.fr

Catherine Roullier

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

catherine.roullier@univ-nantes.fr

Morgane Rousselot

HEMARINA SA

Biotechnopôle

Aéropole Centre

29600 Morlaix

France

morgane.rousselot@hemarina.com

Sandrine Ruchaud

Sorbonne Universités

UPMC Univ Paris 06

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francesandrine.ruchaud@sb-roscoff.fr

and

CNRS

USR 3151

Protein Phosphorylation and Human Diseases

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

Nicolas Ruiz

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

nicolas.ruiz@univ-nantes.fr

Gaëlle Simon

Université de Bretagne Occidentale

Technological Platform of Nuclear Magnetic Resonance, Electron Paramagnetic Resonance and Mass Spectrometry

6, av. Victor Le Gorgeu, CS93837

29238 Brest Cedex 3

France

gaelle.simon@univ-brest.fr

Peter D. Steinberg

University of New South Wales

Centre for Marine Bio-Innovation, School of Biological, Earth and Environmental Science

Sydney

Australia 2052

and

Sydney Institute of Marine Science

Mosman

NSW

Australia 2088

p.steinberg@unsw.edu.au

Torsten Thomas

University of New South Wales

Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Science

Sydney

Australia 2052

t.thomas@unsw.edu.au

Thierry Tonon

Sorbonne Universités

UPMC Univ Paris 06

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

France

and

CNRS

UMR 8227

Integrative Biology of Marine Models

Station Biologique de Roscoff

CS 90074

F-29688 Roscoff cedex

Francetonon@sb-roscoff.fr

Jean Turquet

ARVAM

CYROI, La Technopole

2, rue maxime Rivière

97490 Sainte Clotilde

La Réunion

France

jean.turquet@arvam.com

Marieke Vanstellandt

University of Nantes

Faculty of Pharmacy

MMS, 9 rue Bias

F-44000 Nantes Cedex 1

France

mvansteelandt@yahoo.fr

Gaëtane Wielgosz-Collin

Université de Nantes

9 rue Bias

BP 53508

44035 Nantes

France

wielgosz-collin@univ-nantes.fr

Anne Witzak

Université de Perpignan via Domitia

Laboratoire de chimie des biomolécules et de l'environnement, EA4215

52 avenue Paul Alduy

66860 Perpignan cedex

France

anne.witzak@univ-perp.fr

Franck Zal

HEMARINA SA

Biotechnopôle

Aéropole Centre

29600 Morlaix

France

franck.zal@hemarina.com

Preface

Our original idea was to provide a series of comprehensive chapters, devoted to molecules that are either naturally produced or transformed by marine organisms, each having a recognized influence on human welfare, or having a significant impact on our chemosphere, and thus on depending life forms. The individual chapters would introduce the molecule(s) of interest in its/their historical or its environmental perspective, develop the analytical aspects (chemistry, structure–activity, synthesis), and finally mention the ecological significance and the pertaining biotechnological developments in the light of the existing literature. Graduate students would have access to essential information on a given molecule, all bundled up in a single chapter pointing out useful references for consultation on specific details. Likewise, teachers would be able to structure a complete lecture on a single topic, with references from which they can follow up a specific aspect.

The immediate challenge we had to face was to select 20–25 molecules within the hundreds of eligible candidates. Our second challenge was to contact experts who were willing to spend some of their time and enthusiasm to join our project with at least one contribution. Not an easy task – as excellent textbooks, reviews, handbooks and communications have been published on marine natural products within the past few years. The choice of molecules by our authors naturally fell into three sections: (i) molecules deemed outstanding for their structural originality, their spectral characteristics, or their reactivity and its consequences on synthesis; (ii) molecules that are known to play an important role in isolated organisms or in whole ecosystems; and (iii) molecules that have attracted special interest in the quest for new drugs or new treatments. As the editorial project was being constructed, it was decided that a review of modern analytical approaches, using state-of-the art instrumentation would add a useful complement to the metabolite chapters. Thus, ultimately four Parts were proposed for the book, in which each chapter would be a stand-alone source of information and a useful starting point for someone willing to investigate.

Part One includes six chapters, selected as an assortment based on biodiversity as representative criteria, given the editorial constraints. Cyanobacterial toxins represent a well-known problem in the treatment of freshwater for household and recreational uses, but the occurrence of cyanotoxins in maritime zones is not well documented, and a growing concern for isolated populations which live off their natural resources on a daily basis. The first chapter is devoted to an overview of this subject, by a team of field specialists in association which pharmacologists and neurobiologists (Chapter 1). Highly efficient chemical defenses are produced by microbes or phytoplankton, and concentrated through the food chain, or result from functional interactions between sessile marine organisms and their dedicated microbiomes. In the second chapter are reviewed three major examples of seafood contaminants, which have puzzled generations of investigators and for which prevention remains essential. Some structures are extraordinarily complex, yet highly stable, with surprising bioactivities, as explained by the authors, chemists and pharmacologists who have longstanding experience in working with marine toxins (Chapter 2). The next two chapters deal with marine fungal metabolites, a recently explored source of novel molecules of pharmacological potential. After a review of the importance the genus Penicillium, both as marine fungi and as historical sources of drugs, the first “fungus” chapter expands on three examples of novel structures that have potential as anticancer agents, by leading researchers (Chapter 3). The following chapter explores the hitherto unsuspected source of bioactive drugs from fungi of deep-sea hydrothermal vents, and the biotechnological promises we can anticipate from this newly explored environment – a story told in association between benchtop scientists and field investigators (Chapter 4). The next chapter is devoted to glycoconjugates from marine invertebrates, an often underestimated source of original molecules endowed with bioactivities usually sought in other classes of so-called “secondary metabolites“ (Chapter 5). Part One ends with a very original chapter on molecules found in crinoids which were thought to be extinct since the Triassic–Jurassic extinction event. . .until the unexpected discovery of living representatives in the twentieth century (Chapter 6).

Part Two of the book is devoted to metabolites that have no particular originality in terms of structure, but offer some benefits to the source organism, or act as “positive” communication signals between congeners, or between a host and its microbial associates. On the other hand, some of them have a clearly toxic effect on other taxa, and may be the cause of environmental concern. Leading scientists explore the bases of bacterial communication systems in the first chapter (Chapter 7). In the second chapter, the extraordinary story of the discovery of domoic acid is documented by two pioneers, Steve Bates and Mike Quilliam, and its ecological and pharmacological importance is further examined in the light of the most recent research (Chapter 8). The third chapter introduces us to algal morphoinducers, and to the resemblances and differences of cell differentiation and growth patterns between algae and terrestrial plants (Chapter 9). The fourth and last chapter of this “ecology” Part reviews halogenation processes in marine molecules, from molecular mechanisms involving haloperoxidases, to the biogeoclimatic consequences halogenated molecules have locally (Chapter 10).

In Part Three, more emphasis is placed on the structure–activity and pharmacological applications in which some molecules have recently been involved, during screenings on targets of interest for major and diverse pathologies. The first chapter reviews recent “highlights,” some of which have interesting potential, mostly as inhibitors (Chapter 11). The second chapter provides a prime example of this multifunctionality, as the authors focus on squalamine, an aminosterol produced by dogfish, and which has revealed a wide array of potential therapeutic applications (Chapter 12). The third chapter reviews marine peptides which have been modified to acquire so-called secondary metabolite characteristics, and are actively studied for their potential as anticancer agents. A whole range of microbial and of metazoan examples are reviewed by authors from a group that has gained longstanding expertise in this class of molecules (Chapter 13). Conotoxin venoms and other conopeptides illustrate further the offensive–defensive specialization made by some carnivorous mollusks of these modified peptides, in a well-documented text written by authorities on the subject (Chapter 14). Mycosporine-like amino acids (MAAs) are natural antioxidants and sunscreens used by diverse terrestrial and marine organisms or whole photosystems, enabling them to live totally exposed to solar radiations. The authors focus on MAAs produced by lichens and by reef corals, two models with very different lifestyles (Chapter 15). Next, in the pharmacology applications, is a chapter which relates a successful biotechnological adventure. The authors show how they adapted the hemoglobin produced by a lugworm, to an array of therapeutic applications, from first-aid to the optimal storage of organs prior to transplantation (Chapter 16). The closing chapter for this Part introduces lamellarins, a family of complex alkaloids that were originally produced by didemnid ascidians and which represent a fine example of structure–activity relationship, particularly in relation to sulfation patterns (Chapter 17).

Lastly, Part Four provides a state-of-the art technical complement to whoever extracts, purifies, analyzes, mimics and valorizes marine natural products. The chapter on NMR is written by a team of spectroscopists who have developed a range of tools and approaches to cater for a wide variety of marine samples and address specific challenges posed by fellow chemists and biologists. Through multiple examples, the authors provide a rationale for the treatment of individual situations (Chapter 18). The next three chapters provide a comprehensive overview of “omics”– that is, molecular approaches that can be applied to single cells, organisms (systems biology approach), and to whole ecosystems, in order to study interaction dynamics. The range of analytical techniques (genomes, transcriptomes, proteomes, metabolomes) is explored by a panel of scientists who are leaders in their field, and whose research will undoubtedly revolutionize our examination of the ways in which organisms interact in the oceans (Chapter 19–21). Next, Chapter 22 is devoted to the biosynthesis of natural products, using gene-mining approaches, and is written by world experts in the subject. Finally, a team of young and enthusiastic investigators has devoted the closing chapter to the latest high-throughput screening methods which allow rapid responses to be obtained from a large number of minute samples of molecules exposed to specific molecular targets, especially those that directly control cell division cycles (Chapter 23).

Finally, we wish to thank our fellow members of the French research cluster BioChiMar who responded very rapidly, spared some of their time, and shared their enthusiasm by writing chapters on some of their research or on favorite subjects, for the benefit of others.

Marine natural products is indeed a treasure chest for ecologists to explore, for pharmacologists to investigate, and for humankind to preserve in anticipation of the unprecedented climatic changes that are forecast to occur during the next decades as a consequence of global warming. Undoubtedly, the latter topic will result in massive collapses in species diversity in fragile and complex ecosystems, and especially in areas subjected to direct human interference.

Roscoff and Nantes
January 2014

Stéphane La Barre
Jean-Michel Kornprobst

Related Titles

Outstanding Marine Molecules

Chemistry, Biology, Analysis

List of Contributors

Foreword

Preface

Part One
Outstanding Marine Molecules from a Chemical Point of View