Recent Advances in Polyphenol Research, Volume 6

About the Editors Heidi Halbwirth is Associate Professor at Technische Universität Wien in Vienna, Austria. Her research activities have concentrated on plant secondary metabolism in horticulturally relevant plants with a strong focus on the enzymes involved and their structure-function relationships. Her particular research passion is flower colour, which allows the study of fundamental aspects of plant biochemistry and physiology. Karl Stich is Professor at Technische Universität Wien in Vienna, Austria. His field of expertise is the biochemistry of plants, and applied biochemistry in the field of plant protection with a strong focus on the secondary metabolism of plants. He is a longstanding member of Groupe Polyphenols and was awarded the 11th GP Medal for his scientific contributions to the elucidation of the flavonoid pathway. Véronique Cheynier, former president of the " Groupe Polyphénols " (2012-2016), is research director at the French National Institute for Agricultural Research (INRA) in Montpellier, France. Her research interests concern the study of the structure of polyphenolic compounds, notably vegetable tannins and anthocyanin pigments, their reactions during plant transformation processes, and their influence on the quality of foods and beverages, especially wine. Stéphane Quideau, former president of the " Groupe Polyphénols " (2008-2012), is full professor of Organic and Bioorganic Chemistry at the University of Bordeaux, France. His research laboratory is specialized in plant polyphenol chemistry and chemical biology, with a focus on the studies of ellagitannin chemical reactivity and synthesis, and interactions of bioactive polyphenols with their protein targets.

Contributors xiii

Preface xvii

Acknowledgements xxi

1 The Lignans: A Family of Biologically Active Polyphenolic Secondary Metabolites 1
Anna K.F. Albertson and Jean‐Philip Lumb

1.1 Introduction 1

1.2 Biosynthesis of Lignans 3

1.3 Synthetic Approaches to Lignans and Derivatives 7

1.4 Conclusion 60

References 65

2 Anthocyanin Accumulation is Controlled by Layers of Repression 71
Andrew C. Allan, Kathy E. Schwinn, and Richard V. Espley

2.1 Introduction 71

2.2 MYBs and bHLHs Directly Activate Anthocyanin Production 72

2.3 Exciting Phenotypes in Horticulture are often caused by Variations in the Expression of Key MYBs 73

2.4 Is There a Cost to the Plant of over accumulation of Anthocyanins? 74

2.5 Controlling Anthocyanin Levels 75

2.6 The MYB Activator is Degraded at Night 76

2.7 MYB Activator Competes with MYB Repressors 77

2.8 miRNA‐ Targeted Degradation of MYB Transcript 78

2.9 Turnover of Anthocyanin Vacuolar Content by Peroxidases 78

2.10 Summary 79

References 79

3 The Subtleties of Subcellular Distribution: Pointing the Way to Underexplored Functions for Flavonoid Enzymes and End Products 89
Brenda S.J. Winkel

3.1 Multienzyme Complexes and Metabolic Networks 89

3.2 New Insights from Global Surveys of Protein Interactions 90

3.3 The Flavonoid Metabolon 91

3.4 Subcellular Distribution of Flavonoid Enzymes and Evidence for Alternative Metabolons 94

3.5 Posttranslational Modifications – An Underexplored Area of Flavonoid Metabolism 98

3.6 Why Do We Need to Know? 99

3.7 Future Prospects 99

References 100

4 Transcriptional and Metabolite Profiling Analyses Uncover Novel Genes Essential for Polyphenol Accumulation 109
Wilfried Schwab, Ludwig Ring, and Chuankui Song

4.1 Introduction 109

4.2 Transcriptional and Metabolite Profiling Analyses in Strawberry Fruit 110

4.3 Characterization of Peroxidase 27 113

4.4 Competition of the Lignin and Flavonoid/Anthocyanin Pathways as Demonstrated by the Activity of Peroxidase 27 115

4.5 Candidate Genes Putatively Correlated with Phenolics Accumulation in Strawberry Fruit 115

4.6 Acylphloroglucinol Biosynthesis in Strawberry Fruit 118

4.7 Glucosylation of Acylphloroglucinols 120

4.8 Conclusion

References 124

5 Dietary (Poly)Phenols and Vascular Health 127
Christine Morand, Nicolas Barber‐Chamoux, Laurent‐Emmanuel Monfoulet, and Dragan Milenkovic

5.1 Introduction 127

5.2 Vascular Health: A Prerequisite to Prevent Cardiometabolic Diseases and Cognitive Decline 128

5.3 Diet and Vascular Health 130

5.4 (Poly)Phenols: A Major Family of Dietary Plant Bioactive Compounds 131

5.5 Fate of (Poly)Phenols in the Body and Biological Activities 133

5.6 Nutritional Effects of Flavonoids in Protecting Cardiovascular Health 135

5.7 Limitation of Knowledge and Strategy for Research 138

5.8 Findings from Translational Research on Citrus Flavanones and Vascular Health 139

5.9 Conclusion 142

References 142

6 Cellular‐Specific Detection of Polyphenolic Compounds by NMR‐and MS‐Based Techniques: Application to the Representative Polycyclic Aromatics of Members of the Hypericaceae, the Musaceae and the Haemodoraceae 149
Dirk Hölscher,

6.1 Introduction 149

6.2 The Plant Genus Hypericum 150

6.3 Phenylphenalenones: Plant Secondary Metabolites of the Haemodoraceae 151

6.4 Phenalenone‐ Type Phytoalexins 157

6.5 Laser Microdissection and Cryogenic NMR as a Combined Tool for Cell Type‐Specific Metabolite Profiling 160

6.6 Matrix‐ free UV Laser Desorption/Ionization (LDI) at the Single‐Cell Level: Distribution of Secondary Metabolites of Hypericum Species 163

6.7 LDI‐ MSI‐Based Detection of Phenalenone‐Type Phytoalexins in a Banana– Nematode Interaction 166

6.8 LDI‐ FT‐ICR‐MSI Reveals the Occurrence of Phenylphenalenones in Red Paracytic Stomata 169

6.9 Conclusion 171

6.10 Acknowledgements 171

References 171

7 Metabolomics Strategies for the De replication of Polyphenols and Other Metabolites in Complex Natural Extracts 183
Jean‐Luc Wolfender, Pierre‐Marie Allard, Miwa Kubo, and Emerson Ferreira Queiroz

7.1 Introduction 183

7.2 Metabolite Profiling and Metabolomics 184

7.3 Metabolite Annotation and Dereplication 188

7.4 Targeted Isolation of Original Polyphenols 198

7.5 Conclusion 201

References 201

8 Polyphenols from Plant Roots: An Expanding Biological Frontier 207
Ryosuke Munakata, Romain Larbat, Léonor Duriot, Alexandre Olry, Carole Gavira, Benoit Mignard, Alain Hehn, and Frédéric Bourgaud

8.1 Introduction 207

8.2 Polyphenols in Roots versus Shoots: Not More, Not Less, But Often Different 207

8.3 Allelochemical Functions of Root Polyphenols 213

8.4 Physiological Functions of Root Polyphenols in Plants 217

8.5 Biotechnologies to Produce Root Polyphenols 220

8.6 Conclusion 227

References 227

9 Biosynthesis of Polyphenols in Recombinant Micro‐organisms: A Path to Sustainability 237
Kanika Sharma, Jian Zha, Sonam Chouhan, Sanjay Guleria, and Mattheos A.G. Koffas

9.1 Introduction 237

9.2 Flavonoids 239

9.3 Stilbenes 247

9.4 Coumarins 251

9.5 Conclusion 253

References 254

10 Revisiting Wine Polyphenols Chemistry in Relation to Their Sensory Characteristics 263
Victor de Freitas

10.1 Introduction 263

10.2 Astringency of Polyphenols 265

10.3 Bitter Taste of Polyphenols 269

10.4 Red Wine Colour 271

10.5 Conclusion 276

References 278

11 Advances in Bio‐based Thermosetting Polymers 285
Hélène Fulcrand, Laurent Rouméas, Guillaume Billerach, Chahinez Aouf, and Eric Dubreucq

11.1 Introduction 285

11.2 Industrial Sources of Polyphenols 289

11.3 Principles of Thermoset Production 290

11.4 Relationships between Structure and Reactivity of Polyphenols 292

11.5 Thermosets from Industrial Lignins and Tannins 295

11.6 Depolymerization of Lignins and Tannins to Produce Phenolic Building Blocks and their Glycidylether Derivatives 306

11.7 Development of Dimethyloxirane Monophenols and Bisphenols as Thermosetting Building Blocks 310

11.8 Conclusion 322

References 323

12 Understanding the Misunderstood: Products and Mechanisms of the Degradation of Curcumin 335
Claus Schneider

12.1 Introduction 335

12.2 Degradation of Curcumin – A Historical and Personal Perspective 336

12.3 The Degradation is an Autoxidation 341

12.4 Novel Products of the Degradation/Autoxidation of Curcumin 344

12.5 Transformation of Curcumin to Bicyclopentadione 348

12.6 A Proposed Mechanism for the Autoxidation of Curcumin 350

12.7 Microbial Degradation of Curcumin 354

12.8 Conclusion 357

References 357

13 How to Model a Metabolon: Theoretical Strategies 363
Julien Diharce and Serge Antonczak

13.1 Introduction 363

13.2 Localization 364

13.3 Existing Structures 365

13.4 Three‐ Dimensional Structures of Enzymes: Homology Modelling 367

13.5 Modes of Access to Active Sites: Randomly Accelerated Molecular Dynamics 370

13.6 Protein– Protein Association: Protein–Protein Docking 372

13.7 Substrate Channelling and Molecular Dynamics 374

13.8 Metabolon 378

13.9 Conclusion 379

References 381

Index 387