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Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants

1. Aufl.

von: Erick J. Vandamme, José Luis Revuelta
178,99 €
Verlag:	Wiley-VCH
Format:	EPUB
Veröffentl.:	26.07.2016
ISBN/EAN:	9783527681778
Sprache:	englisch
Anzahl Seiten:	578

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Beschreibungen

Titelbeschreibung

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.

Inhaltsverzeichnis

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

Autorenportrait

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.