Outstanding Marine Molecules E-Book
160,99 €
Mehr erfahren.
- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Using a number of outstanding examples, this text introduces readers to the immense variety of marine natural compounds, the methodologies to characterize them and the approaches to explore their industrial potential. Care is also taken to discuss the function and ecological context of the compounds.
Carefully produced and easy to read, this book serves students and professionals wishing to familiarize themselves with the field, and is ideally suited as a course book for both industry to academia.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 1604
Veröffentlichungsjahr: 2014
Ähnliche
CONTENTS
Cover
Related Titles
Title Page
Copyright
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 Introduction
1.2 Marine Cyanobacteria as Causative Agent of Ciguatera-Like Poisoning
1.3 Marine Cyanobacteria: A Potential Risk for Swimmers
1.4 Microcystins Could also be Found in the Sea
1.5 Risk of Neurodegenerative Disease in the Sea
1.6 Conclusion and Future Prospects
Acknowledgments
References
Chapter 2: Outstanding Marine Biotoxins: STX, TTX, and CTX
2.1 Introduction
2.2 Saxitoxins (STXs) in Paralytic Shellfish Poisoning
2.3 Tetrodotoxin (TTX) in Puffer Fish Poisoning (PFP)
2.4 Ciguatoxin (CTX) in Ciguatera Fish Poisoning (CFP)
2.5 Conclusions
References
Chapter 3: Impact of Marine-Derived
Penicillium
Species in the Discovery of New Potential Antitumor Drugs
3.1 Introduction
3.2 Molecules Isolated from Marine-Derived Penicillium Species With Potent Cytotoxic Activity
3.3 Marine-Derived Cytotoxic Penicillium
3.4 What are these Promising Molecules from Marine Penicillium?
3.5 Conclusions
References
Chapter 4: Astonishing Fungal Diversity in Deep-Sea Hydrothermal Ecosystems: An Untapped Resource of Biotechnological Potential?
4.1 Introduction
4.2 Deep-Sea Hydrothermal Vents as Life Habitats
4.3 The Five “W”s of Marine fungi: Who? What? When? Where? Why?
4.4 Fungi in Deep-Sea Hydrothermal Vents
4.5 Conclusions
Acknowledgments
References
Chapter 5: Glycolipids from Marine Invertebrates
5.1 Introduction
5.2 Glycosphingolipids from Marine Invertebrates: Occurrence, Characterization, and Biological Activity
5.3 Gangliosides
5.4 Atypical Glycolipids
5.5 General Conclusion
List of Abbreviations
References
Chapter 6: Pigments of Living Fossil Crinoids
6.1 The Discovery of Stalked Crinoids
6.2 Anthraquinonic Pigments of Stalked Crinoids
6.3 Axial Chirality of Gymnochromes and Hypochromines
6.4 Towards a Fungal Origin of Gymnochromes?
6.5 Biological Activities of Gymnochromes
6.6 Perspectives
References
Part Two: Outstanding Marine Molecules from an Ecological Point of View
Chapter 7: Bacterial Communication Systems
7.1 Coordination of Multicellular Behavior in Bacteria
7.2 The Repertoire of Chemical Signals
7.3 Molecular Mechanisms of QS
7.4 The Effective Range of QS-Regulated Processes
7.5 The Inhibition of QS: Quorum Quenching
7.6 Examples of Cross-Kingdom Signaling in the Marine Environment
7.7 “-Omic” Approaches to QS
7.8 Concluding Remarks
References
Chapter 8: Domoic Acid
8.1 Historical Background
8.2 Case Studies
8.3 Chemistry
8.4 DA-Producing Organisms
8.5 Molecular Basis of DA Acute and Chronic Poisoning
8.6 Understanding and Predicting Toxigenic Diatom Blooms (Macroscopic Scale)
8.7 Natural Factors that Enhance Bloom Formation and/or DA Production
8.8 Functional Genomics of Diatoms
8.9 Conclusions
Note added in proof
Acknowledgments
References
Chapter 9: Algal Morpho-Inducers
9.1 Introduction
9.2 Morpho-Inducers of Animals and Land Plants Produced by Macroalgae
9.3 Morpho-Inducers of Macroalgae
9.4 Conclusions
Acknowledgment
References
Chapter 10: Halogenation and Vanadium Haloperoxidases
10.1 Introduction
10.2 Biochemical Characterization of Vanadium-Dependent Haloperoxidases (VHPOs)
10.3 Structural Characterization of VHPOs
10.4 Catalytic Cycle and Halide Specificity
References
Part Three: Outstanding Marine Molecules with Particular Biological Activities Outstanding
Chapter 11: Promising Marine Molecules in Pharmacology
11.1 Introduction
11.2 Promising Substances Isolated from Microorganisms
11.3 Promising Substances Isolated from Macroalgae and Invertebrates
11.4 Promising Substances Synthesized from Natural Models
11.5 Conclusion
References
Chapter 12: Promises of the Unprecedented Aminosterol Squalamine
12.1 Introduction
12.2 Discovery of the Unprecedented Aminosterol Squalamine
12.3 Syntheses of Squalamine
12.4 Biological Activities
12.5 Mechanism of Antiangiogenic Activity of Squalamine
12.6 Preclinical Studies of Squalamine
12.7 Clinical Studies of Squalamine
12.8 Bioactive Potential of Trodusquemine, a Natural Squalamine Derivative
12.9 Conclusion
References
Chapter 13: Marine Peptide Secondary Metabolites
13.1 Introduction
13.2 Ribosomal- and Nonribosomal-Derived Peptides: A Virtually Unlimited Source of New Active Compounds
13.3 Laxaphycins and their Derivatives: Peptides Not So Easy to Synthesize
13.4 Dolastatins: From Deception to Hope Through Structural Modification Leading to Reduced Toxicity
13.5 Didemnins and Related Depsipeptides: How Perseverance Should Lead to Their Low-Cost Production
13.6 Kahalalide F: A Study in Chemical Ecology as a Starting Point for New Antitumoral Agent Discovery
13.7 Azole/Azoline-Containing Cyanobactins Isolated from Invertebrates: An Example of Nature's Own Combinatorial Chemistry
13.8 Conclusion
Acknowledgments
References
Chapter 14: Conotoxins and Other Conopeptides
14.1 Background
14.2 Diversity of Conopeptides
14.3 Isolation Techniques
14.4 Conopeptide Three-Dimensional Structures
14.5 Conopeptide Pharmacological Activities
14.6 Outlook
Acknowledgments
Notes
References
Chapter 15: Mycosporine-Like Amino Acids (MAAs) in Biological Photosystems
15.1 Background
15.2 Chemistry
15.3 MAA-Producing Organisms
15.4 Hermatypic Corals: Living Under Tight Constraints
15.5 Lichenic Systems: Living in the Extremes
15.6 Modes of Action and Applications to Human Welfare
15.7 Conclusions
Acknowledgments
15.A
Appendix 15A.1 Precursors and degradation products
Appendix 15A.2 Carbon thirteen data of Mycosporines and Mycosporine-like Amino Acids
References
Chapter 16: Extracellular Hemoglobins from Annelids, and their Potential Use in Biotechnology
16.1 Introduction
16.2 Annelid Extracellular Hemoglobins
16.3 Architecture
16.4 Model of Quaternary Structures
16.5 Biotechnology Applications
16.6 Organ Preservation
16.7 Anemia
16.8 Conclusion
Acknowledgments
References
Chapter 17: Lamellarins: A Tribe of Bioactive Marine Natural Products
17.1 Introduction
17.2 Lamellarins: Bioactive Marine Natural Products
17.3 Anticancer Activities of Lamellarins
17.4 Inhibition of Topoisomerase I by Lamellarins
17.5 Inhibition of Protein Kinases by Lamellarins
17.6 Lamellarin-induced Mitochondrial Perturbations
17.7 Antiviral Activity of Sulfated Lamellarins
17.8 Synthesis of Lamellarins
17.9 Non-Natural Lamellarin Analogs
17.10 Conclusion
References
Part Four: New Trends in Analytical Methods
Chapter 18: NMR to Elucidate Structures
18.1 Introduction
18.2 NMR to Elucidate Structures
18.3 Sample Preparation
18.4 Conventional “Liquid” Probes: Obtaining 1D and 2D Spectra of all NMR-Observable Nuclei
18.5 Cryoprobes: Obtaining 1D and 2D Spectra Mainly in
1
H1,
13
C
18.6 HRMASNMR: Obtaining 1H, 13C, 31P, 15N 1D and 2D Spectra
18.7 CPMASNMR: Obtaining all NMR Observable Nuclei Spectra
18.8 Conclusion
References
Chapter 19: An Introduction to Omics
19.1 What are “Omics”?
Notes
References
Chapter 20: Gene Mining for Environmental Studies and Applications: Examples from Marine Organisms
20.1 Introduction
20.2 Techniques
20.3 Current Applications
20.4 Conclusions and Outlook
References
Chapter 21: Proteomics and Metabolomics of Marine Organisms: Current Strategies and Knowledge
21.1 Introduction
21.2 General Strategies for Proteomics and Peculiarities of the Marine Environment
21.3 General Strategies for Metabolomics, and Peculiarities of the Marine Environment
21.4 Conclusions
Acknowledgments
References
Chapter 22: Genomics of the Biosynthesis of Natural Products: From Genes to Metabolites
22.1 Introduction
22.2 Biosynthesis of PKs, NRPs and RiPPs: Basic Principles
22.3 Connecting Genes and Metabolites: Selected Examples of Aquatic Natural Product Biosynthesis
22.4 Conclusions and Perspectives
Abbreviations
References
Chapter 23: High-Throughput Screening of Marine Resources
23.1 Introduction
23.2 High-Throughput Screening and Drug Development
23.3 Examples of High-Throughput Screening
23.4 Conclusions and Perspectives
List of Abbreviations
Acknowledgments
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
Guide
Cover
Table of Contents
Preface
Part 1: Outstanding Marine Molecules from a Chemical Point of View
Chapter 1: Marine Cyanotoxins Potentially Harmful to Human Health
Pages
ii
iii
iv
xiii
xiv
xv
xvi
xvii
xviii
xix
xx
xxi
xxii
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
Related Titles
Kornprobst, J.-M.
Encyclopedia of Marine Natural Products
2 Edition
2014
Print ISBN: 978-3-527-33429-2, also available as digital format
Berger, S., Sicker, D.
Classics in Spectroscopy
Isolation and Structure Elucidation of Natural Products
2009
Print ISBN: 978-3-527-32516-0
Bertini, I., McGreevy, K.S., Parigi, G. (eds.)
NMR of Biomolecules
Towards Mechanistic Systems Biology
2012
Print ISBN: 978-3-527-32850-5
ISBN: 978-3-527-64450-6, also available as digital format
Kornprobst, J.-M.
Encyclopedia of Marine Natural Products
3 Volume Set
2010
Print ISBN: 978-3-527-32703-4
Outstanding Marine Molecules
Chemistry, Biology, Analysis
Edited by
Stéphane La Barre
Jean-Michel Kornprobst
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty can be created or extended by sales representatives or written sales materials. The Advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Card No.: applied for
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Bibliographic information published by the Deutsche Nationalbibliothek
The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley's global Scientific, Technical, and Medical business with Blackwell Publishing.
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978-3-527-33465-0
ePDF ISBN: 978-3-527-68152-5
ePub ISBN: 978-3-527-68153-2
mobi ISBN: 978-3-527-68151-8
obook ISBN: 978-3-527-68150-1
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
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
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
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
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
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
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
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
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
Stephen S. Bates
Fisheries and Oceans Canada
Gulf Fisheries Centre
P.O. Box 5030
Moncton
New Brunswick
E1C 9B6 Canada
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
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
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
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
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
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
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
Alyssa Carré-Mlouka
National Museum of Natural History
75005 Paris
France
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
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
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
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
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
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
David J. Craik
The University of Queensland
Institute for Molecular Bioscience
Brisbane
QLD 4072
Australia
Cécile Debitus
Institut de Recherche pour le Développement
UMR 241
BP 529, 98713 Papeete
Polynésie Française
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
Sergey Dobretsov
Sultan Qaboos University
P. O. Box 50
Muscat 123
Oman
Virginia. P. Edgcomb
Woods Hole Oceanographic Institution
Geology and Geophysics Department
Woods Hole
MA 02543
USA
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
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
Stjepko Golubic
Boston University
Biological Science Center
5 Cummington Street
Boston
MA 02215
USA
Olivier Grovel
University of Nantes
Faculty of Pharmacy
MMS, 9 rue Bias
F-44000 Nantes Cedex 1
France
Muriel Gugger
Institut Pasteur, Collection des Cyanobacteéries
Dé??partement de Microbiologie
28 rue du Dr Roux
75015 Paris
France
Yann Guitton
University of Nantes
Faculty of Pharmacy
MMS, 9 rue Bias
F-44000 Nantes Cedex 1
France
Tilmann Harder
University of New South Wales
Centre for Marine Bio-Innovation, School of Biological, Earth and Environmental Science
Sydney
Australia 2052
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
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
Quentin Kaas
The University of Queensland
Institute for Molecular Bioscience
Brisbane
QLD 4072
Australia
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
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
Jean-Michel Kornprobst (Editor)
Institut Mer et Littoral
Bâtiment Isomer2, rue de la Houssiniére
44322 Nantes BP 92208 Cedex 3France
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
Dominique Laurent
Institut de Recherche pour le Développement (IRD)
Pharma-Dev UMR 152
BP529, 98713 Papeete
Tahiti
French Polynesia
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
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
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
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
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
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
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
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
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
Yves-François Pouchus
University of Nantes
Faculty of Pharmacy
MMS, 9 rue Bias
F-44000 Nantes Cedex 1
France
Michael Quilliam
National Research Council Canada
Measurement Science and Standards
1411 Oxford Street
Halifax
Nova Scotia
B3 H 3Z1 Canada
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
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
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
Catherine Roullier
University of Nantes
Faculty of Pharmacy
MMS, 9 rue Bias
F-44000 Nantes Cedex 1
France
Morgane Rousselot
HEMARINA SA
Biotechnopôle
Aéropole Centre
29600 Morlaix
France
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
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
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
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
Torsten Thomas
University of New South Wales
Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Science
Sydney
Australia 2052
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
Jean Turquet
ARVAM
CYROI, La Technopole
2, rue maxime Rivière
97490 Sainte Clotilde
La Réunion
France
Marieke Vanstellandt
University of Nantes
Faculty of Pharmacy
MMS, 9 rue Bias
F-44000 Nantes Cedex 1
France
Gaëtane Wielgosz-Collin
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
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
Franck Zal
HEMARINA SA
Biotechnopôle
Aéropole Centre
29600 Morlaix
France
Foreword
Natural products (secondary metabolites) which once were focused on alkaloids and terpenes now cover an infinite molecular diversity, and are merging with primary metabolites through “omics” connections. Today, it is assumed that druggable molecules can also be a matter of bioinspired thinking through close and synergistic partnerships between chemists, biologists and chemical ecologists. Unfortunately, the discovery of new scientific concepts, novel analytical approaches or simply of state-of-the-art techniques tends to be overemphasized, overestimated or overpublicized, relegating essential questioning and basic concerns to the background. In the case of natural products, the isolation of new molecules is currently greatly hampered by this shift in focus, and we feel that the quest for new natural structures (i.e., sourcing) should be actively maintained in the face of pending climate- or humankind-driven habitat degradations and biodiversity destruction. The structural determination of natural new molecules is vital, given its considerable importance for any biological investigation, and includes an understanding of the ecosystems that function at the molecular level and the development of rational products for the treatment of diseases. While structural determination can be achieved more quickly by spectroscopic and crystallographic means, the acquisition of adequate funding for natural products projects is becoming increasingly difficult for both industrial and academic communities alike. The paradox is that the demand for new active molecules is now heralded as a major priority!
Recent advances in organic chemistry and in metabolomics analyses, together with the advent of the postgenomic era, now make it possible to envisage a critical role for natural products chemistry in chemical biology and in chemical ecology, with a timely integration into the multidisciplinary systems biology approach. But, can all of this be envisaged without knowing the structure of the molecule? The answer is definitely: no!
In this book is presented a selection of marine molecules which have attracted the attention of a wide panel of reputed scientists worldwide, and especially within the national research network that I am proud to have managed for several years. To the series of comprehensive chapters on marine molecules, deemed outstanding for their interesting structures, their amazing bioactivities, or their environmental significance, critical and highly documented reviews of modern laboratory experimentation have been added. It is hoped that this contribution will provide inspiration to the generation of new scientists and motivate them to embrace a meaningful human health-oriented career, or to invent environmentally dedicated tools and approaches for the benefit of all.
Ali Al-MourabitDirector of BioChiMar NetworkNatural Product Chemistry Institute (ICSN)Department of Natural Products & Medicinal Chemistry (SNCM)Research Center of the CNRS at Gif sur YvetteFranceDecember 2013
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 NantesJanuary 2014
Stéphane La BarreJean-Michel Kornprobst
Part OneOutstanding Marine Molecules from a Chemical Point of View
1Marine Cyanotoxins Potentially Harmful to Human Health
Mélanie Roué, Muriel Gugger, Stjepko Golubic, Zouher Amzil, Romulo Aráoz, Jean Turquet, Mireille Chinain, and Dominique Laurent
Abstract
Many people around the world depend on the marine environment, for its nutritional, recreational, and general economic value. For many years, a notable increase has been observed in the number of cases of severe intoxication, through the consumption of contaminated seafood and through external exposure. While dinoflagellates and diatoms are considered the main source of marine biotoxins, there is also growing evidence that certain groups of marine cyanobacteria are likely to produce various toxins with potential harmful effects on humans, especially in cases of massive proliferation. Some of the recent findings that support this hypothesis are summarized in this chapter.
1.1 Introduction
Many people around the world depend on the marine environment, for its nutritional, recreational, and general economic value. This is especially true in tropical regions, where the economy is highly dependent on seafood for subsistence, for the local export industry, and for tourism. Although fish and shellfish are an essential nutritional resource to the populations of islands and coastal regions, a notable increase in numbers of cases of severe poisoning related to the consumption of seafood during recent years has forced these populations to modify their eating habits. In French Polynesia, for example, the reduction of fishing in coral reefs and lagoons and the increased reliance on imported food instead, may have already contributed to the rising prevalence of chronic diseases such as diabetes, hypertension and cardiovascular diseases in indigenous Pacific populations (Chinain et al., 2010).
Cyanobacteria (formerly “blue-green algae”) occupy a wide range of marine, freshwater, and terrestrial habitats. They are ubiquitous in marine ecosystems, where they play a major role in oxygen production and the fixation of atmospheric carbon and nitrogen. Cyanobacteria proliferating in marine environments represent an important source of structurally diverse bioactive secondary metabolites (Burja et al., 2001; Tan, 2007; Uzair et al., 2012), with over 800 compounds identified (Jones et al., 2010). However, compared to freshwater cyanobacteria, relatively little attention has been paid to the toxicity of marine cyanobacteria as a human health hazard.
Microalgae – in particular dinoflagellates but also diatoms (Fritz et al., 1992) – are considered to be the main source of marine biotoxins, particularly those that are biomagnified (i.e., accumulated and concentrated) along the food chain, and are at the origin of many human poisoning syndromes, such as Ciguatera Fish Poisoning, which is highly prevalent in the Pacific. The question is: Could marine cyanobacteria also have the ability to biosynthesize toxins? And if so, are they able to contaminate seafood such as to become potentially harmful to human health? Marine cyanobacteria are an enormous source of ever-increasing bioactive compounds that include cytotoxins, neurotoxins and dermatotoxins, among others (Shimizu, 2003; Nunnery, Mevers, and Gerwick, 2010). However, to date, no human mortality related to cyanobacterial marine toxins has been demonstrated. Some cyanobacterial isolates in freshwater (and brackish environments) are known to produce cyanotoxins and are a public health hazard when ingested with drinking water, leading to severe human or livestock poisonings (Falconer and Humpage, 2005; Funari and Testai, 2008). In addition, they can be fatal through hemodialysis (Azevedo et al., 2002), recreational exposure, or accumulation in food (Funari and Testai, 2008). There is recent evidence that marine cyanobacteria can indeed have harmful effects on humans through the consumption of contaminated seafood and through external exposure, especially in cases of massive proliferation (Figure 1.1).
Figure 1.1 Headlines about the harmful effects of marine cyanobacteria on humans through the consumption of contaminated seafood (French Polynesia, New-Caledonia) and through external exposure (Mayotte). (a) © La Dépêche, no. 791, March 7th, 2010; (b) © Les Nouvelles Calédoniennes, November 11th, 2011; (c) © Cellule de l'Institut de Veille Sanitaire en Région Océan Indien, BVS no. 9, February, 2012 (according to Lernout et al., 2012); (d) © M. Valo, Le Monde, August 20th, 2012.
1.2 Marine Cyanobacteria as Causative Agent of Ciguatera-Like Poisoning
1.2.1 Ciguatera Fish Poisoning
Ciguatera Fish Poisoning (CFP) is the most common marine foodborne disease, and is responsible for more cases of human poisonings than all other marine toxins combined (Fleming et al., 2006; EFSA, 2010). While CFP occurs primarily in tropical regions of the South Pacific Ocean, Indian Ocean and Caribbean Sea (Lewis, 2001), its incidence rates have recently been shown to be increasing in temperate regions (Aligizaki, Nikolaidis, and Fraga, 2008; Dickey and Plakas, 2010; Boada et al., 2010). CFP is classically known to result from the ingestion of tropical coral reef fish contaminated with ciguatoxins (CTXs) (Figure 1.2). CTXs are heat-stable polyethers mainly produced by microalgal benthic dinoflagellates belonging to the genus Gambierdiscus (Yasumoto et al., 1977; Bagnis et al., 1980, Holmes et al., 1991) (Figure 1.3). These toxins are further transferred through the marine food web to herbivorous and then to carnivorous fish (Litaker et al., 2010). Human poisoning typically occurs after the consumption of herbivorous or carnivorous toxic fish (Randall, 1958; Bagnis et al., 1980). CTXs are potent activators of voltage-sensitive sodium channels (VSSCs), and cause an increase of the neuronal excitability and neurotransmitter release (Nicholson and Lewis, 2006). Through the food web, significant biotransformations of Gambierdiscus-produced CTXs occur by oxidative changes, enhancing their potency (Mills, 1956, Yasumoto et al., 2000). Symptoms of CFP intoxication include a combination of more than 30 gastrointestinal, neurological and general medical disturbances (Bagnis, Kuberski, and Laugier, 1979; Gillepsie et al., 1986; Quod and Turquet, 1996); the most typical of these include temperature reversal sensations, paresthesia, pruritus, asthenia, and gastrointestinal disturbances. The severity of CFP symptoms depends on a combined influence of ingested dose, toxin profiles, and individual susceptibility.
Figure 1.2 Chemical structure of ciguatoxin P-CTX-3C.
Figure 1.3 Microphotograph of a Gambierdiscus sp. cell, the toxic dinoflagellate responsible for the production of ciguatoxins. Image © Institut Louis Malardé.
The realization that ciguatera-type fish and clam poisoning, intensified by an accumulation along the food chain, may be caused by benthic cyanobacteria rather than dinoflagellates came as recently as 2005 (Laurent et al., 2005). Between 2001 and 2005, the villagers of the tribe of Hunëtë village in the island of Lifou (Loyalty Islands, New Caledonia) had observed that many cases of seafood poisoning that occurred following the consumption of giant clams or of grazing and molluskivorous fish, resembled the familiar CFP. However, the villagers were surprised by the severity of the symptoms, the elevated number of hospitalizations, and by the inefficiency of traditional remedies. On their initiative, the Institut de Recherche pour le Développement (IRD) conducted a thorough environmental survey of the affected area and found an outward-expanding degradation of the coral reef environment. No evidence of the presence of Gambierdiscus blooms was found; rather, large populations of benthic cyanobacteria of the genus Hydrocoleum Kützing were present (Laurent et al., 2005; Laurent et al., 2008; Laurent et al., 2012).
Although early studies from many research groups had shown Gambierdiscus spp. and dinoflagellates to be the primary causative agents of CFP intoxications (Yasumoto et al., 1977; Bagnis et al., 1980), cyanobacteria were actually suspected first. Randall (1958) assumed that a benthic organism, most likely a blue-green alga, was the source of the toxin responsible for CFP. When, in 1964, a group of 33 people in Bora Bora Island (French Polynesia) were seriously poisoned following consumption of the giant clam Tridacna maxima (Tridacnidae), Bagnis (1967) emphasized the presence of blue-green algae covering the giant clams in a limited area of the lagoon containing ciguateric fishes. This was also the first report of the implication of giant clams in ciguateric intoxications with a triple vasomotor, digestive and nervous syndrome that was in agreement with the typical syndromes of CFP. In the same year, based on the presence of the benthic cyanobacterium Lyngbya majuscula in the gut of a large number of poisonous fishes, Halstead (1967) hypothesized that these cyanobacteria might produce CTXs.
During the 1990s, two experimental studies showed for the first time that a marine pelagic cyanobacterium, Trichodesmium erythraeum, could – just as Gambierdiscus dinoflagellates – be a potential source of toxins in CFP (Hahn and Capra, 1992; Endean et al., 1993). Hahn and Capra (1992) demonstrated typical signs of CFP intoxication in mice injected intraperitoneally with extracts from T. erythraeum and from mollusk samples collected during and shortly after the cyanobacterial bloom. Endean et al. (1993) demonstrated that the toxin profiles of extracts from T. erythraeum were similar to the corresponding fractions obtained from the flesh of the plankton-eating fish Scomberomorus commersoni (mullet, Mugilidae). Mullet are known to graze on Trichodesmium blooms, and are often implicated with CFP intoxications. This observation was later confirmed by the detection of CTXs-like compounds in Trichodesmium blooms collected in New Caledonian waters, where cases of CFP intoxications following the ingestion of mullets have been reported (Kerbrat et al., 2010). Planktonic Trichodesmium and benthic Hydrocoleum, recently observed in a toxic area of Lifou, New Caledonia, where inhabitants were intoxicated, are the most common bloom-forming filamentous cyanobacteria in tropical seas. They are morphologically similar, closely related with respect to 16 S rRNA gene (Abed et al., 2006), and are also both toxic. Plankton blooms of Trichodesmium are subject to drift by wind and currents to the coasts.
Recently, an interrelationship between the disturbances of the reef ecosystem, the presence of benthic cyanobacterial blooms (Figure 1.4), and the occurrence of CFP-like incidents was observed in different regions of the South Pacific: New Caledonia (Lifou island), French Polynesia (Raivavae and Rurutu islands) and Republic of Vanuatu (Emao island) (Chinain et al., 2010; Laurent et al., 2012). Finally, Ehrenreich et al. (2005) documented that diverse marine and freshwater cyanobacteria possess the sequences of gene fragments from nonribosomal peptide synthetases (NRPS) and modular polyketide synthases (PKS). The construction of CTXs is achieved via the polyketide pathway and thus probably involves PKS; these results thus support the hypothesis that many cyanobacteria – just as the dinoflagellates – could be a potential source of CTXs, or CTX-like compounds.
Figure 1.4 Benthic cyanobacterial blooms observed in Raivavae and Rurutu islands (French Polynesia), showing field aspects (left) and corresponding microscopic images of the organisms (right). (a) Marine benthic Anabaena sp. forming partially detached fibrous mats; (b) Mats of Aulosira schauinslandii Lemmermann 1905, a marine benthic heterocystous cyanobacterium first described from Hawaii; (c) Oscillatoria bonnemaisonii Crouan ex Gomont forms loose, bright red colonies which may fuse into contiguous covers; (d) Hydrocoleum cantharidosmum (Montagne) Gomont (genetically close to planktonic Trichodesmium), one of several toxic populations forming mats. Microscopic images © S. Golubic.
CTXs detection and quantification remains a difficult issue due to the wide range of congeners present in trace amounts in contaminated matrices. Presently, several detection methods are available with varying sensitivity and selectivity. These include the mouse bioassay (MBA), the receptor-binding assay (RBA), the cell-based assay (CBA) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), as well as various immunological assays (see Caillaud et al., 2010 for a review). The gene cluster encoding ciguatoxins is still unknown. However, the construction of these polyketides is achieved via the polyketide pathway and thus probably involves PKS with some additional functional segments (Lopez-Legentil et al., 2010). A hybrid NRPS and PKS gene was, for example, characterized from the toxic dinoflagellate Karenia brevis which produces brevetoxins – polyketides that show very strong structural homologies with ciguatoxins (Lopez-Legentil et al., 2010).
According to the current EU legislation, fishery products containing biotoxins, such as ciguatoxins, are not to be introduced to the market (Paredes et al., 2011). Currently, the European Food Safety Authority (EFSA) could not characterize the risk associated with CTXs, because of the scarce data available (EFSA, 2010). However, the presence of CTX in fish from the Madeira Archipelago (Europe) was recently confirmed for the first time (Otero et al., 2010). In other parts of the world, there are only a few specific regulations for CTX, although some bans have been installed as public health measures, such as the prohibition of selling high-risk fish species coming from known toxic locations. These bans have been installed in American Samoa, Queensland, French Polynesia, Fiji, Hawaii, and Miami (Paredes et al., 2011).
1.2.2 Ciguatera Shellfish Poisoning (CSP): A New Ecotoxicological Phenomenon
Epidemiological studies conducted in New Caledonia (Lifou), French Polynesia (Raivavae) and the Republic of Vanuatu (Emao) have suggested a link between disturbances of the reef ecosystem, the development of oscillatoriacean cyanobacterial blooms, and an increase in ciguatera-like incidents following the consumption of giant clams from contaminated areas (Laurent et al., 2008; Kerbrat et al., 2010; Chinain et al., 2010; Laurent et al.
