Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants
, by Vandamme, Erick J.; Revuelta, José; Luis
- ISBN: 9783527337347 | 3527337342
- Cover: Hardcover
- Copyright: 4/25/2016
Vitamins are a group of physiologically very important, chemically quite complex organic compounds, that are essential for humans and animals. Some vitamins and other growth factors behave as antioxidants, while some can be considered as biopigments. As their chemical synthesis is laborious, their biotechnology-based synthesis and production via microbial fermentation has gained substantial interest within the last decades. Recent progress in microbial genetics and in metabolic engineering and implementation of innovative bioprocess technology has led to a biotechnology-based industrial production of many vitamins and related compounds. Divided into three sections, this volume covers:
1. water-soluble vitamins
2. fat-soluble vitamin compounds and
3. other growth factors, biopigments, and antioxidants.
They are all reviewed systematically: from natural occurrence and assays, via biosynthesis, strain development, to industrially-employed biotechnological syntheses and applications.
1. water-soluble vitamins
2. fat-soluble vitamin compounds and
3. other growth factors, biopigments, and antioxidants.
They are all reviewed systematically: from natural occurrence and assays, via biosynthesis, strain development, to industrially-employed biotechnological syntheses and applications.
Erick J. Vandamme is Emeritus Professor at the Department of Biochemical and Microbial Technology, Faculty Bioscience Engineering, Ghent University, Belgium. He has acted as director of this department for over 25 years. He was Visiting Professor at several universities in Europe, America, Asia, and Australia. Following his Ph.D. studies at Ghent University in molecular biology, fermentation science and industrial biotechnology, several postdoctoral positions led him to Oxford University, MIT Cambridge, and Queen Elisabeth College (now King's College), London. Professor Vandamme is (co)-author of over 400 research papers and review articles , (co-)edited 14 books and holds several patents. He received numerous scientific awards and is an Elected Fellow of the American Academy of Microbiology (USA) and of the Society for Industrial Microbiology and Biotechnology, and received three honorary doctorates. He is a member of the Royal Flemish Academy of Belgium for Science and the Arts .
Jose L. Revuelta is Full Professor of Genetics, Chairman of the Metabolic Engineering Group, and Director of the New Generation Sequencing Laboratory at the University of Salamanca (Spain) since 2002. Upon receipt of his Ph.D. in 1981 at Leon University in Biological Sciences, he received a grant by the Juan March Foundation to perform postdoctoral training at The Scripps Clinic and Research Foundation (La Jolla, CA). Professor Revuelta is coauthor of more than 50 research papers and review articles in the field of vitamins biotechnology, genomics and chemogenomics of industrial microorganisms. He coauthored eight chapters in books related with the biotechnological production of vitamins and pigments and holds 21 patents related to vitamin B2 production.
Jose L. Revuelta is Full Professor of Genetics, Chairman of the Metabolic Engineering Group, and Director of the New Generation Sequencing Laboratory at the University of Salamanca (Spain) since 2002. Upon receipt of his Ph.D. in 1981 at Leon University in Biological Sciences, he received a grant by the Juan March Foundation to perform postdoctoral training at The Scripps Clinic and Research Foundation (La Jolla, CA). Professor Revuelta is coauthor of more than 50 research papers and review articles in the field of vitamins biotechnology, genomics and chemogenomics of industrial microorganisms. He coauthored eight chapters in books related with the biotechnological production of vitamins and pigments and holds 21 patents related to vitamin B2 production.
List of Contributors XIX
Preface XXVII
1 Vitamins, Biopigments, Antioxidants and Related Compounds: A Historical, Physiological and (Bio)technological Perspective 1
Erick J. Vandamme and José L. Revuelta
1.1 Historical Aspects of the Search for Vitamins 1
1.2 Vitamins: What’s in a Name 3
1.3 Physiological Functions of Vitamins and Related Compounds 6
1.4 Technical Functions of Vitamins and Related Compounds 8
1.5 Production and Application of Vitamins and Related Factors 8
1.6 Outlook 13
References 13
Part I Water-Soluble Vitamins 15
2 Industrial Production of Vitamin B2 by Microbial Fermentation 17
José L. Revuelta, Rodrigo Ledesma-Amaro, and Alberto Jiménez
2.1 Introduction and Historical Outline 17
2.2 Occurrence in Natural/Food Sources 17
2.3 Chemical and Physical Properties; Technical Functions 18
2.4 Assay Methods and Units 18
2.5 Biological Role of Flavins and Flavoproteins 19
2.6 Biotechnological Synthesis of Riboflavin 21
2.6.1 Riboflavin-Producing Microorganisms 21
2.6.2 Biosynthesis of Riboflavin 22
2.6.3 Regulation of the Biosynthesis of Riboflavin 25
2.7 Strain Development: Genetic Modifications, Molecular Genetics and Metabolic Engineering 26
2.8 Fermentation Process 31
2.9 Downstream Processing 32
2.10 Chemical Synthesis 33
2.11 Application and Economics 33
References 33
3 Vitamin B3, Niacin 41
Tek Chand Bhalla and Savitri
3.1 Introduction 41
3.2 History 42
3.3 Occurrence in Nature/Food Sources 43
3.4 Chemical and Physical Properties 44
3.4.1 Chemical Properties 44
3.4.2 Physical Properties 44
3.5 Vitamin B3 Deficiency Disease (Pellagra) 45
3.6 Methods Used for Determination of Vitamin B3 46
3.6.1 Microbiological Methods 46
3.6.2 Chemical Methods 46
3.7 Synthesis 47
3.7.1 Chemical Process Used for Nicotinic Acid Production 47
3.7.2 Biosynthesis 49
3.7.2.1 Biological Processes Used for Nicotinic Acid Production 49
3.8 Downstream Processing of Nicotinic Acid 52
3.9 Reactive Extraction 53
3.10 Physiological Role of Vitamin B3 (Niacin) 53
3.10.1 Coenzyme in Metabolic Reactions 53
3.10.2 Therapeutic Molecule 56
3.10.2.1 Treatment of Pellagra 56
3.10.2.2 Treatment of Cardiovascular Diseases 57
3.10.2.3 Antihyperlipidemic Effect 57
3.10.2.4 Treatment of Hypercholesterolemia 57
3.10.2.5 Diabetes 58
3.10.2.6 Fibrinolysis 58
3.10.2.7 Treatment of Neurodegenerative Disorders 58
3.11 Safety of Niacin 59
3.12 Toxicity of Niacin 59
3.12.1 Hepatotoxicity 59
3.12.2 Vasodilation/Niacin Flush 59
3.12.3 Glucose Intolerance 60
3.13 Derivatives of Niacin 60
3.14 Application in Cosmetics, Food and Feed 61
3.15 Future Prospects 61
References 61
4 Pantothenic Acid 67
Jesus Gonzalez-Lopez, Luis Aliaga, Alejandro Gonzalez-Martinez, and Maria V. Martinez-Toledo
4.1 Introduction and Historical Outline 67
4.2 Occurrence in Natural Food Sources and Requirements 71
4.3 Physiological Role as Vitamin or as Coenzyme 74
4.4 Chemical and Physical Properties 77
4.5 Assay Methods 79
4.6 Chemical and Biotechnological Synthesis 81
4.7 Application and Economics 92
References 98
5 Folate: Relevance of Chemical and Microbial Production 103
Maddalena Rossi, Stefano Raimondi, Luca Costantino, and Alberto Amaretti
5.1 Introduction 103
5.2 Folates: Chemical Properties and Occurrence in Food 103
5.3 Biosynthesis 105
5.4 Physiological Role 106
5.5 Bioavailability and Dietary Supplements 109
5.6 Chemical and Chemoenzymatic Synthesis of Folic Acid and Derivatives 110
5.7 Intestinal Microbiota, Probiotics and Vitamins 114
5.8 Folate Production by Lactic acid Bacteria 115
5.9 Folate Production by Bifidobacteria 117
5.10 Conclusions 120
References 124
6 Vitamin B12 – Physiology, Production and Application 129
Janice Marie Sych, Christophe Lacroix, and Marc J.A. Stevens
6.1 Introduction and Historical Outline 129
6.2 Occurrence in Food and Other Natural Sources 130
6.3 Physiological Role as a Vitamin or Coenzyme 131
6.3.1 Absorption and Transport 131
6.3.2 Metabolic Functions 132
6.3.3 Main Causes and Prevalence of Deficiencies 133
6.3.4 Diagnosis of Deficiencies 134
6.4 Chemical and Physical Properties 134
6.5 Assay Methods 137
6.6 Biotechnological Synthesis 140
6.6.1 Producing Microorganisms 140
6.6.1.1 Propionibacteria (PAB) 142
6.6.1.2 Pseudomonades 143
6.6.2 Biosynthesis and Metabolic Regulation 144
6.6.3 Engineering of B12 Production 145
6.6.3.1 Propionibacteria 145
6.6.3.2 Pseudomonades 146
6.6.4 Fermentation Process 146
6.6.4.1 Propionibacteria 146
6.6.4.2 Pseudomonades 148
6.7 Downstream Processing; Purification and Formulation 149
6.8 Application and Economics 150
6.9 Conclusions and Outlook 151
References 151
7 Industrial Fermentation of Vitamin C 161
Weichao Yang and Hui Xu
7.1 Introduction and Historical Outline 161
7.2 Occurrence in Natural/Food Sources 162
7.2.1 Occurrence of Asc in Foods 162
7.2.2 Biosynthesis of Asc in Plants and Mammals 164
7.3 Physiological Role of Asc 164
7.4 Chemical and Physical Properties 165
7.5 Assay Methods 165
7.6 Industrial Fermentation of Asc 166
7.6.1 The Reichstein Process:The Major Industrial Asc Process until the Late 1990s 167
7.6.1.1 The Establishment of the Reichstein Process 167
7.6.1.2 Bioconversion of D-Sorbitol to L-Sorbose by Gluconobacter 167
7.6.1.3 The Key Enzyme of Gluconobacter for L-Sorbose Production 168
7.6.1.4 Oxidation of L-Sorbose to 2-KLG and Rearrangement to Asc 168
7.6.2 The Two-Step Fermentation Process for Asc Production 168
7.6.2.1 The First Step of Fermentation: Conversion of D-Sorbitol to L-Sorbose 169
7.6.2.2 The Second Step of Fermentation: Conversion of L-Sorbose to 2-Keto-L-Gulonic acid 170
7.6.2.3 Strain Development: Genetic Modification, Molecular Genetics and Metabolic Engineering 175
7.6.2.4 Fermentation Process 177
7.6.2.5 Upstream and Downstream Processing 181
7.7 Application and Economics 182
7.8 Outlook 183
References 185
8 Direct Microbial Routes to Vitamin C Production 193
Günter Pappenberger and Hans-Peter Hohmann
8.1 Introduction and Scope 193
8.2 Principles of Direct L-Ascorbic Acid Formation:The Major Challenges 195
8.2.1 Stereochemistry of L-Ascorbic Acid 195
8.2.2 Enzymes Producing L-Ascorbic Acid and Their By-Product Spectrum 196
8.3 Direct L-Ascorbic Acid Formation via 1,4-Lactones 197
8.3.1 L-Ascorbic Acid Forming Enzymes: 1,4-Lactone Oxidoreductases 198
8.3.2 Direct L-Ascorbic Acid Formation in HeterotrophicMicroalgae 200
8.3.3 Direct L-Ascorbic Acid Formation in Recombinant Yeast 201
8.3.4 Direct L-Ascorbic Acid Formation from Orange Processing Waste in Recombinant Aspergillus niger 203
8.3.5 Overall Conclusion on 1,4-Lactone Routes 204
8.4 Direct L-Ascorbic Acid Formation via 2-Keto Aldoses 206
8.4.1 L-Ascorbic Acid Forming Enzymes: L-Sorbosone Dehydrogenases 208
8.4.1.1 Sndhak 208
8.4.1.2 Sndhai 211
8.4.1.3 Prevalence of L-Asc Forming Sorbosone Dehydrogenases in Nature 211
8.4.2 L-Asc or 2-KGA from L-Sorbosone: One Substrate, Several Isomers, Two Products 212
8.4.3 L-Sorbose Dehydrogenase, Accumulating L-Sorbosone 215
8.4.3.1 Ssdh from K. vulgare 215
8.4.3.2 Sorbose Dehydrogenase Sdh from G. oxydans 217
8.4.4 Gluconobacter as Host for Direct L-Ascorbic Acid Formation 217
8.5 Outlook 219
Acknowledgement 220
References 220
Part II Fat Soluble Vitamins 227
9 Synthesis of ��-Carotene and Other Important Carotenoids with Bacteria 229
Christoph Albermann and Holger Beuttler
9.1 Introduction 229
9.2 Carotenoids: Chemical Properties, Nomenclature and Analytics 230
9.2.1 Nomenclature 231
9.2.2 Analysis of Carotenoids 231
9.2.2.1 Handling Precautions 231
9.2.2.2 Extraction 232
9.2.2.3 Chromatography Methods for Analysis of Carotenoids 233
9.3 Natural Occurrence in Bacteria 234
9.4 Biosynthesis of Carotenoids in Bacteria 236
9.5 Biotechnological Synthesis of Carotenoids by Carotenogenic and Non-Carotenogenic Bacteria 239
9.5.1 Heterologous Expression of Carotenoid Biosynthesis Genes 240
9.5.2 Increased Isoprenoid Precursor Supply 243
9.5.3 Genome-Wide Modification of E. coli to Increase Carotenoid Formation 244
9.5.4 Balancing Recombinant Enzyme Activities for an Improved Synthesis of Carotenoids by E. coli 249
9.5.5 Production of Industrially Important Carotenoids by Other Recombinant Bacteria 252
9.5.6 Culture Conditions of Improved Formation of Carotenoids by Recombinant Bacteria 252
9.6 Conclusion 253
References 254
10 ��-Carotene and Other Carotenoids and Pigments from Microalgae 265
Borhane Samir Grama, Antoine Delhaye, Spiros N. Agathos, and Clayton Jeffryes
10.1 Introduction and Historical Outline 265
10.2 Occurrence in Nature and Food Sources 266
10.3 Physiological Role as a Vitamin or as a Coenzyme 267
10.4 Chemical and Physical Properties; Technical Functions 268
10.5 Assay Methods and Units 270
10.6 Biotechnological Synthesis 270
10.6.1 Producing Organisms 270
10.6.2 Biosynthesis and Metabolic Regulation 273
10.6.3 Strain Development: Genetic Modification, Molecular Genetics and Metabolic Engineering 276
10.6.4 Downstream Processing, Purification and Formulation 276
10.7 Chemical Synthesis or Extraction 279
10.8 Process Economics 279
References 280
11 Microbial Production of Vitamin F and Other Polyunsaturated Fatty Acids 287
Colin Ratledge
Lipid Nomenclature 287
11.1 Introduction: Essential Fatty Acids 288
11.2 General Principles for the Accumulation of Oils and Fats in Microorganisms 294
11.3 Production of Microbial Oils 297
11.3.1 Production of Gamma-Linolenic Acid (GLA; 18 : 3 n-6) 297
11.3.2 Productions of Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA) 300
11.3.3 Alternative Sources of DHA 302
11.3.4 Production of Eicosapentaenoic Acid (EPA n-3) 305
11.3.5 Prospects of Photosynthetic Microalgae for Production of PUFAs 307
11.4 Safety Issues 310
11.5 Future Prospects 312
Acknowledgements 315
References 316
12 Vitamin Q10: Property, Production and Application 321
Joong K. Kim, Eun J. Kim, and Hyun Y. Jung
12.1 Background of Vitamin Q10 321
12.1.1 Historical Aspects 321
12.1.2 Definition 321
12.1.3 Occurrence 322
12.1.3.1 In Nature 322
12.1.3.2 In Food Sources 322
12.1.3.3 In Microorganisms 326
12.1.4 Functions 326
12.2 Chemical and Physical Properties of CoQ10 326
12.2.1 Chemical Properties 326
12.2.2 Physical Properties 327
12.3 Biosynthesis and Metabolic Regulation of CoQ10 327
12.3.1 Biosynthesis of CoQ10 327
12.3.1.1 Microorganisms 327
12.3.1.2 Biosynthetic Pathways 329
12.3.2 Metabolic Regulation 334
12.3.3 Strain Development 335
12.3.3.1 Mutagenesis 335
12.3.3.2 Genetic Modification 335
12.3.3.3 Metabolic Engineering 337
12.3.4 Fermentation Process 339
12.3.5 Upstream and Downstream Processing 340
12.3.5.1 Upstream Processing 340
12.3.5.2 Downstream Processing 343
12.4 Chemical Synthesis and Separation of CoQ10 345
12.4.1 Chemical Synthesis 345
12.4.2 Solvent Extraction 346
12.4.3 Purification 350
12.5 Applications and Economics of CoQ10 351
12.5.1 Applications 351
12.5.1.1 In Diseases 351
12.5.1.2 In Cosmetics 352
12.5.1.3 In Foods and Others 353
12.5.2 Economics 354
References 355
13 Pyrroloquinoline Quinone (PQQ) 367
Hirohide Toyama
13.1 Introduction and Historical Outline 367
13.2 Occurrence in Natural/Food Sources 367
13.3 Physiological Role as Vitamin or as Bioactive Substance 368
13.4 Physiological Role as a Cofactor 373
13.5 Chemical and Physical Properties; Technical Functions 376
13.6 Assay Methods 377
13.7 Biotechnological Synthesis 377
13.7.1 Producing Microorganisms 377
13.7.2 Biosynthesis and Metabolic Regulation 378
13.8 Strain Development: Genetic Modification, Molecular Genetics and Metabolic Engineering 378
13.9 Up- and Down-stream Processing; Purification and Formulation 380
13.10 Chemical Synthesis or Extraction Technology 380
13.11 Application and Economics 380
References 381
Part III Other Growth Factors, Biopigments and Antioxidants 389
14 L-Carnitine, the Vitamin BT: Uses and Production by the Secondary Metabolism of Bacteria 391
Vicente Bernal, Paula Arense, and Manuel Cánovas
14.1 Introduction and Historical Outline 391
14.2 Occurrence in Natural/Food Sources 392
14.3 Physiological Role as Vitamin or as Coenzyme 393
14.3.1 Physiological Role of Carnitine in the Mitochondria 393
14.3.2 Physiological Role of Carnitine in the Peroxisomes 394
14.3.3 Other Functions of Carnitine 394
14.4 Chemical and Physical Properties 394
14.5 Assay Methods and Units 395
14.5.1 Chromatographic Methods 395
14.5.2 MS-Based Methods 395
14.5.3 Enzymatic Methods 398
14.5.4 Automated Methods 399
14.6 Biotechnological Synthesis of L-Carnitine Microbial Metabolism of L-Carnitine and Its Regulation 399
14.6.1 Biotechnological Methods for L-Carnitine Production 399
14.6.1.1 De novo Biosynthesis of L-Carnitine 399
14.6.1.2 Biological Resolution of Racemic Mixtures 399
14.6.1.3 Biotransformation from Non-Chiral Substrates 400
14.6.2 Roles of L-Carnitine in Microorganisms 401
14.6.2.1 Protectant Agent 401
14.6.2.2 Carbon and Nitrogen Source 401
14.6.2.3 Electron Acceptor: Carnitine Respiration 402
14.6.3 L-Carnitine Metabolism in Enterobacteria and Its Regulation 403
14.6.3.1 Metabolism of L-Carnitine in E. coli 403
14.6.3.2 Metabolism of L-Carnitine in Proteus sp. 405
14.6.4 Expression of Metabolising Activities: Effect of Inducers, Oxygen and Substrates 406
14.6.5 Biotransformation with D-Carnitine or Crotonobetaine as Substrates 406
14.6.6 Transport Phenomena for L-Carnitine Production 407
14.6.6.1 Membrane Permeabilisation 407
14.6.6.2 Osmotic Stress Induction of Transporters 408
14.6.6.3 Overexpression of the Transporter caiT 408
14.6.7 Metabolic Engineering for High-Yielding L-Carnitine Producing Strains 408
14.6.7.1 Link between Central and Secondary Metabolism during Biotransformation 408
14.6.7.2 Metabolic Engineering for Strain Engineering: Feedback between Modelling and Experimental Analysis of Cell Metabolism 409
14.7 Other Methods for L-Carnitine Production: Extraction from Natural Sources and Chemical Synthesis 411
14.7.1 Isolation of L-Carnitine from Natural Sources 411
14.7.2 Chemical Synthesis 411
Acknowledgement 412
References 412
15 Application of Carnosine and Its Functionalised Derivatives 421
Isabelle Chevalot, Elmira Arab-Tehrany, Eric Husson, and Christine Gerardin
15.1 Introduction and Historical Outline 421
15.2 Sources and Synthesis 422
15.2.1 Occurrence in Natural/Food Sources 422
15.2.2 Chemical Synthesis of Carnosine 422
15.2.3 Enzymatic Synthesis of Carnosine 423
15.3 Physico-Chemical and Biological Properties of Carnosine 425
15.3.1 Physico-Chemical Properties 425
15.3.2 Physiological Properties 426
15.4 Biotechnological Synthesis of Carnosine Derivatives: Modification, Vectorisation and Functionalisation 427
15.4.1 Chemical Functionalisation 427
15.4.2 Enzymatic Functionalisation: Enzymatic N-Acylation of Carnosine 430
15.4.2.1 Lipase-Catalysed N-Acylation of Carnosine in Non-Aqueous Medium 431
15.4.2.2 Acyltransferase-Catalysed N-Acylation of Carnosine in Aqueous Medium 432
15.4.2.3 Impact of Enzymatic Oleylation of Carnosine on Some Biological Properties 434
15.4.3 Vectorisation 434
15.5 Applications of Carnosine and Its Derivatives 435
15.5.1 Nutraceutics and Food Supplementation 435
15.5.2 Cosmetics 436
15.5.3 Pharmaceuticals 436
References 438
16 Metabolism and Biotechnological Production of Gamma-Aminobutyric Acid (GABA) 445
Feng Shi, Yalan Ni, and Nannan Wang
16.1 Introduction 445
16.2 Properties and Occurrence of GABA in Natural Sources 446
16.3 Metabolism of GABA 447
16.3.1 Biosynthesis and Export of GABA 450
16.3.1.1 Biosynthesis of GABA 450
16.3.1.2 Essential Enzyme for GABA Biosynthesis – GAD 451
16.3.1.3 Export of GABA 452
16.3.2 Uptake and Catabolism of GABA 454
16.3.2.1 The Uptake System of GABA 454
16.3.2.2 The Catabolism of GABA 455
16.4 Regulation of GABA Biosynthesis 456
16.5 Biotechnological Production of GABA 457
16.5.1 Fermentative Production of GABA by LAB 458
16.5.2 Production of GABA by Enzymatic Conversion 459
16.5.2.1 Production of GABA by Immobilised GAD 459
16.5.2.2 Improving GAD Activity by Rational and Irrational Designs 459
16.5.3 Fermentation of GABA by Recombinant C. glutamicum 460
16.6 Physiological Functions and Applications of GABA 461
16.6.1 Physiological Functions of GABA 461
16.6.2 Applications of GABA 462
16.7 Conclusion 462
Acknowledgement 462
References 463
17 Flavonoids: Functions,Metabolism and Biotechnology 469
Celestino Santos-Buelga and Ana M. González-Paramás
17.1 Introduction 469
17.2 Structure and Occurrence in Food 471
17.3 Activity and Metabolism 476
17.4 Biosynthesis of Flavonoids in Plants 481
17.5 Biotechnological Production 484
17.5.1 Reconstruction of Flavonoid Pathways in Plant Systems 485
17.5.2 Reconstruction of Flavonoid Pathways in Microbial Systems 487
17.5.2.1 E. coli Platform 487
17.5.2.2 Saccharomyces cerevisiae Platform 489
17.6 Concluding Remarks 489
References 490
18 Monascus Pigments 497
Yanli Feng, Yanchun Shao, Youxiang Zhou,Wanping Chen, and Fusheng Chen
18.1 Introduction and History of Monascus Pigments 497
18.2 Categories of MPs 497
18.3 Physiological Functions of MPs 498
18.3.1 Anti-Cancer Activities 498
18.3.2 Antimicrobial Activities 508
18.3.3 Anti-Obesity Activities 509
18.3.4 Anti-Inflammation Activities 510
18.3.5 Regulation of Cholesterol Levels 510
18.3.6 Anti-Diabetes Activities 511
18.4 Chemical and Physical Properties of MPs 511
18.4.1 Solubility 511
18.4.2 Stability 511
18.4.2.1 Effects of Temperature, pH and Solvent on Stability of MPs 511
18.4.2.2 Effect of Light on Stability of MPs 512
18.4.2.3 Effect of Metal Ion on Stability of MPs 513
18.4.3 Safety 513
18.5 Assay Methods and Units of MPs 513
18.5.1 Extraction and Detection of MPs 513
18.5.2 Isolation and Purification of MPs Components 514
18.5.2.1 CC and TLC 514
18.5.2.2 HPLC 515
18.5.2.3 CE and the Others 515
18.5.3 Identification of MPs Components 515
18.6 MPs Producer – Monascus spp. 520
18.6.1 Brief Introduction of Monascus Species and Their Applications 520
18.6.2 Producing Methods of MPs 520
18.6.3 Progress of Monascus spp. at the Genetic Level 521
18.6.3.1 DNA Transformation 521
18.6.3.2 Citrinin Synthesis and Its Regulations 521
18.6.3.3 MK Synthesis and Its Regulations 522
18.6.3.4 MPs Synthesis and Its Regulation 522
18.6.3.5 The Regulation of Secondary Metabolism in Monascus spp. 523
18.6.4 Monascus Genomics 524
18.7 Application and Economics of MPs 524
Acknowledgements 524
References 526
Index 537
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