Microbial Nutraceuticals

Sudhir Pratap Singh is Professor in the Department of Industrial Biotechnology at the Gujarat Biotechnology University in Gandhinagar, Gujarat, India. He works in gene mining and biocatalyst engineering for enzymatic production of industrial biomolecules. Santosh Kumar Upadhyay is Assistant Professor in the Department of Botany at Panjab University in Chandigarh, India. He works in plant molecular biology for the isolation and characterization and recombinant production of various defense related and industrial proteins.

• About the Editors xvPreface xvii1 Microbial Nutraceuticals: An Overview 1Ashish Kumar Singh, Santosh Kumar Upadhyay, and Sudhir Pratap Singh1.1 Introduction 11.1.1 Overview of Microbial Nutraceuticals 11.2 Microbial Production of Nutrients 21.2.1 Microbial Amino Acid and Peptide Production 21.2.2 Dietary Short- Chain Fatty Acid Production 31.3 Oligosaccharide Production 31.3.1 Prebiotic Oligosaccharide Molecule Production in Microbial Cells 31.3.2 Microbial Transformation and Bio- production of High- Value Rare Functional Sugars: Sources, Methods, and Safety Aspects 41.3.3 Microbial Production of High- Value Polyphenolics 51.3.4 Specialized Carbohydrate Production 51.3.5 Polymeric Nutraceuticals 61.4 Advanced Nutraceutical Products and Processes 61.4.1 Functional Nutraceutical Products 61.4.2 Specialized Nutrient Molecules 81.5 Safety and Regulatory Aspects 101.6 Alternative Sources 10Acknowledgements 11References 112 Microbial Cell Factories for the Production of Essential Amino Acids 23Susana Calderón- Toledo, César Salcedo- Okuma, and Amparo Iris Zavaleta2.1 Introduction 232.2 Essential Amino Acid Biosynthesis 242.2.1 Methionine 242.2.2 Valine 252.2.3 Tryptophan 272.2.4 Phenylalanine 282.2.5 Lysine 292.2.6 Leucine 302.2.7 Threonine 312.2.8 Isoleucine 332.2.9 Histidine 342.3 Fermentation Strategies 342.4 Perspectives and Challenges 35References 363 Microbial Production of Dietary Short- Chain Fatty Acids 45Alexandra Wallimann3.1 Background 453.2 SCFA Generation and Its Producing Microbes 463.2.1 Acetate 463.2.2 Propionate 463.2.3 Butyrate 463.2.4 Valerate 473.2.5 Formate 473.3 Mechanism of Actions 483.4 Impact on Host Health 483.5 Potential of SCFAs as Therapeutics 493.6 Conclusions and Perspectives 50References 504 Microbial Sources for Bioactive Peptides Conferring Health Benefits 55Amin Abbasi, Hadi Pourjafar, Hamideh Fathi Zavoshti, Sara Bazzaz, Parmis Mirzaei, Elham Sheykhsaran, and Hedayat Hosseini4.1 Introduction 554.2 Overview of Bioactive Peptides 564.3 Production and Processing of Bioactive Peptides 584.3.1 Enzymatic Hydrolysis 584.3.2 Microbial Fermentation 594.4 The Role of LAB Proteolytic Systems in the Liberation of Bioactive Peptides 604.5 Purification and Identification 614.6 Promising Health- Promoting Effects 624.6.1 Hypocholesterolemic and Hypolipidemic Effects 624.6.2 Antithrombotic Effect 634.6.3 Antihypertensive Activity 634.6.4 Mineral- Binding Activity 654.6.5 Opiate- Like Activity 654.7 The Impact of Processing Procedures on the Bioactivity of Peptides 664.8 Possible Bioactive Peptide Applications 674.9 One Advancement Over Linear Peptides with Cyclic Peptides 684.10 Computer- based Methods for Peptide Research Utilization 694.11 Challenges in Bioactive Peptide Development 704.12 Conclusions and Future Perspectives 70References 715 Prebiotic Oligosaccharide Production in Microbial Cells 81Avijeet S. Jaswal, Saroj Mishra, and R. Elangovan5.1 Oligosaccharides as Prebiotics 815.2 Structural Diversity of Prebiotic Oligosaccharides and Mechanism of Action 825.2.1 Structures of Various Existing and Emerging Prebiotics 835.2.1.1 Galactooligosaccharides 835.2.1.2 Fructooligosaccharides 835.2.1.3 Chitooligosaccharides 845.2.1.4 Malto- and Isomaltooligosaccharides 845.2.1.5 Mannooligosaccharides 845.2.1.6 Raffinose Family Oligosaccharides 845.2.1.7 Xylooligosaccharides 855.2.2 General Mechanisms of Action of Prebiotics 855.3 Enzymes Involved in the Production of GOSs and FOSs 885.4 Microbial Systems for the Synthesis of GOSs and FOSs 905.4.1 Production of GOSs Using Bacterial and Fungal Systems 915.4.2 Production of FOSs Using Bacterial and Fungal Systems 935.4.2.1 FOSs Production in Bacterial Systems 945.4.2.2 FOSs Production in Fungal Systems 955.5 Novel Prebiotic Oligosaccharides 975.5.1 Pectic Oligosaccharides 975.5.2 Resistant Starch 985.5.3 Polydextrose 985.5.4 Polyphenols and Flavanols 985.5.5 Lactulose 995.5.6 Human Milk Oligosaccharides 995.5.7 Synbiotics 995.5.8 Mushrooms 1005.6 Future Perspectives 100References 1016 Bio- production of Rare Sugars, Applications, Safety, and Health Benefits 115Sweety Sharma, Satya Narayan Patel, Suresh D. Pillai, Jyoti Yadav, and Sudhir Pratap Singh6.1 Introduction 1156.2 d-Allulose 1156.2.1 Physiological Functions and Health Benefits 1176.2.1.1 Anti- obesity and Antidiabetic Effects 1196.2.1.2 Anti- hyperlipidemic Effects 1196.2.1.3 Anti- inflammatory and Antioxidative Effects 1196.3 d- Allose 1196.3.1 Physiological Functions and Health Benefits 1206.3.1.1 Anticancer and Antitumor Properties 1206.3.1.2 Antioxidant Properties 1226.3.1.3 Anti- inflammatory Effects 1226.3.1.4 Cryoprotective, Immunosuppressive, and Other Characteristics 1226.3.1.5 Sweetener and Food Additive 1226.3.1.6 Benefits of d- Allose in Plants 1226.4 Trehalose 1226.4.1 Physiological Functions and Health Benefits 1236.4.1.1 Cryopreservation 1236.4.1.2 Blood Sugar and Insulin Response 1256.4.1.3 Regulation of Glucose Homeostasis and Lipid Metabolism 1256.4.1.4 Antioxidant and Anti- inflammatory Effects 1256.4.1.5 Gut Microbiome Modulation 1256.4.1.6 Dental Health and Weight Management 1256.4.1.7 Stress Regulator in Plants 1266.5 d- Tagatose 1266.5.1 Physiological Functions and Health Benefits 1276.5.1.1 Oral Health 1276.5.1.2 Prebiotic and Systemic Health 1276.5.1.3 Antiaging 1286.5.1.4 d- Tagatose Restricts Plant Pathogen 1286.6 d- Talose 1286.7 Turanose 1296.7.1 Physiological Functions 1296.7.1.1 Blood Sugar Control and Weight Management 1296.7.1.2 Anti- inflammatory Properties 1296.7.1.3 Prebiotic Effects 1296.7.1.4 Gut and Dental Health 1306.7.1.5 Pathogen Detection 1306.7.1.6 Honey Authentication 1316.7.1.7 Food Processing and Osmoprotection 1316.8 Conclusion 131References 1317 Microbial Engineering for the Production of High- value Polyphenolics 145Deepak Sharma, Shweta Kamboj, Maninder Jeet Kaur, Ranju Kumari Rathour, and Nitish Sharma7.1 Introduction 1457.2 Properties and Classification of Polyphenols 1467.2.1 Phenolic Acid 1477.2.2 Flavonoids 1487.2.3 Non- flavonoids 1487.3 Sources of Polyphenols 1487.3.1 Plant as a Source for Polyphenols 1497.3.2 Microbes as Polyphenol Source 1497.4 Metabolic Engineering of Bacteria for Polyphenol Production 1527.4.1 Genetic Engineering Approach for Polyphenol Production in Bacteria 1537.4.2 Genetic Engineering of Fungi for Polyphenol Production 1547.5 Model Organisms for Polyphenol Production 1557.5.1 Yeast 1567.5.2 Escherichia coli 1577.5.3 Corynebacterium Glutamicum 1577.6 Examples of Some Important Polyphenols Produced in E. coli 1577.7 Conclusion and Future Directions 158References 1588 Microbial Approaches for Lactose Transformation into High- value Rare Sugars 167Ashutosh Kumar Singh, Amit Kumar Rai, and Sudhir Pratap Singh8.1 Introduction 1678.2 Lactose- derived Rare Sugar Production Through Microbial Approach 1688.2.1 Lactosucrose 1688.2.2 Tagatose 1698.2.3 Lactulose 1738.2.4 Epilactose 1748.3 Conclusion 176Acknowledgements 176References 1769 Engineering Microbial Pathways for the Production of 2′- Fucosyllactose 183Vijaya Bharathi Srinivasan, Balvinder Singh, and Govindan Rajamohan9.1 Introduction 1839.1.1 Human Milk Oligosaccharides (HMOs) 1839.1.2 Biological Properties and Functions of 2′- FL 1849.2 Human Milk Microbiome 1859.2.1 Chemical Synthesis of 2′- FL 1859.2.2 Enzymatic Synthesis of 2′- FL 1869.2.3 Biological Production of 2′- FL Through Genetic Engineering Strategies 1879.2.4 Engineering Gram- Negative Bacterial Host [Escherichia coli] for 2′- FL Production 1879.2.5 Engineering Gram- Positive Bacterial Host for 2′- FL Production 1899.2.6 Engineering Yeast for 2′- FL Production 1899.2.7 Global Regulatory Approval, Commercialization, Market Value, and Application of 2′- FL 1909.3 Challenges or Future Outlook 1919.4 Conclusion and Perspectives 192Acknowledgement 193References 19310 Microbial Production of Human Milk Oligosaccharides (HMOs) 197Prakram Singh Chauhan, Tripti Dadheech, and Arunika Saxena10.1 Introduction 19710.2 Type and Structure of HMOs 19810.3 Different Methods for HMO Production 20010.3.1 Chemical Synthesis 20010.3.2 Enzymatic Synthesis (Chemoenzymatic HMO Synthesis) 20310.3.2.1 Glycosyltransferase 20310.3.2.2 Glycosidase 20510.3.3 Microbial Cell Factories (Whole- Cell Reaction Method) 20610.3.3.1 2′- Fucosyllactose 20810.4 Strategies for Enhanced HMO Production 21110.4.1 Designing Cell Factories for Commercial Synthesis 21210.4.2 Modification of Metabolic Pathway 21210.4.2.1 Exploitation of Lactose Substrate for Producing HMOs 21210.4.2.2 Engineering of GDP- l- Fucose Pool Occurring Inside a Cell 21210.4.2.3 Transferase Expression and Engineering 21310.4.2.4 Exporting Product Outside Cell 21310.4.3 Process of Fermentation and Scaling- up 21310.4.4 Quality of the Product and Downstream Processes 21410.5 Purification Methods 21410.6 Global Demand and Recent Market Aspects of HMOs 21510.6.1 HMOs’ Market Segmental Analysis 21610.6.2 HMO Market Analysis by Product 21610.6.3 HMOs’ Market Regional Analyzes None 21710.6.4 Factors Affecting the HMOs’ Market 21710.6.5 Dairy Oligosaccharide Industry Restrictions 21710.6.6 Competition Landscape of the Global Human Milk Oligosaccharides’ (HMOs’) Market 21710.6.7 Latest Trends in the HMO Market 21810.6.8 Highlights of Global HMOs’ Market 21810.7 Applications of HMOs 21810.7.1 Functions of HMOs 21910.7.2 Involvement of HMOs as if Prebiotics 21910.7.3 Antiadhesive and Antimicrobial Characteristics of HMOs 22010.7.4 HMO’s Impact on Intestinal Epithelial Cells 22110.7.5 HMO’s Influence on Immune Cells 22110.8 Conclusion and Future Outlook 221References 22211 Beta (β)- glucan as Microbial Polymer with Nutraceutical Potential: Chemistry, Biosynthesis, Extraction, Identification, and Industrial Production of Bioactive Compound for Human Health 231Pawan Prabhakar, Deepak Kumar Verma, and Mamoni Banerjee11.1 Introduction 23111.2 Classification, Chemistry, and Biosynthesis of β- glucan 23311.2.1 Biosynthesis of β- glucan in Bacteria 23411.2.2 Biosynthesis of β- glucan in Fungi 23511.2.3 Biosynthesis of β- glucan in Microalgae 23511.3 Extraction, Isolation, and Identification of β- glucan from Microbial Source 23611.4 Biotechnological Process for the Production of β- glucan from Microbes 23911.4.1 Bacteria 23911.4.2 Fungi 24011.4.3 Microalgae 24311.5 Pharmacological and Nutritional Properties of β- glucan 24311.5.1 Anticancerous 24311.5.2 Antihyperglycemic Effect 24411.5.3 Antihypercholesterolemic and Anti- obesity 24511.5.4 Antioxidant Activity 24611.5.5 Immunomodulatory Activities 24611.5.6 Antimicrobial Activity 24611.6 Future Prospective β- glucan as Microbial Nutraceuticals 24711.7 Concluding Remarks 248Contribution of Authors 248Conflict of Research Interests 248References 24812 Multifaceted Role of Synbiotic Products with Nutraceutical Impact 257Mariana Buranelo Egea, Josemar Gonçalves de Oliveira Filho, and Ailton Cesar Lemes12.1 Introduction 25712.2 Beneficial Effects and Selection Criteria 25812.2.1 Beneficial Effects 25812.2.2 Selection Criteria of Prebiotic, Probiotic, and Synbiotics 25912.3 Human Synbiotic Types 26012.3.1 Main Prebiotics for Human Consumption 26112.3.2 Main Probiotics for Human Consumption 26212.3.3 Main Combinations of Probiotics and Prebiotics in Synbiotic Products 26312.4 Mechanism of Action of Synbiotics 26312.5 Action of Synbiotics in Humans 26412.6 Final Considerations 267Acknowledgment 268References 26813 Postbiotic Supplements with Nutraceutical Significance 273Amin Abbasi, Hedayat Hosseini, Hadi Pourjafar, Leili Aghebati Maleki, Atiyeh Ghafouri Ghotbabad, Sahar Sabahi, Parvin Orojzade, and Mohammadreza Ziavand13.1 Introduction 27313.2 Biological Actions of Postbiotics 27413.2.1 In Vitro Investigations of Bioactivities 27413.2.2 In Vivo Investigation of Bioactivities 27813.2.2.1 Infection Prevention 28013.2.2.2 Infection of Enteric 28013.2.2.3 Allergic Reactions 28113.2.2.4 Infections of Respiratory Tract 28213.2.2.5 Gastroenteritis 28213.2.2.6 Further Clinical Applications 28313.2.3 Postbiotics in Childhood 28413.2.3.1 Principal Applications of Postbiotics in Children 28413.2.3.2 Postbiotics for the Health of Newborns and Premature Infants 28613.3 Gut Dysbiosis Therapy Based on Mineral- Enriched Postbiotics 28613.4 Promising Use of Postbiotics in the Medical or Pharmaceutical Sectors 28913.5 Safety Regulations and Terminology Challenges 29113.6 Conclusion 293References 29314 Innovative Approaches for the Microbial Production of Carotenoids 301Rajni Kumari, Monika, V Vivekanand, and Nidhi Pareek14.1 Introduction to Microbial Carotenoid Production 30114.2 Carotenoids: A Structure- based Approach to Biosynthesis 30314.3 Microbial Sources of Carotenoid Production 30514.4 Factors Affecting Microbial Production of Carotenoid 30614.5 Approaches for Enhancement of Carotenoid Production 30714.5.1 Metabolic Pathway Engineering 30914.5.2 Gene Overexpressing and Knockout 31014.5.3 Fed- Batch and Continuous Fermentation 31114.5.4 Consortia Engineering 31114.5.5 CRISPR- Cas Genome Editing 31214.5.6 Stress Induction 31214.5.7 Directed Evolution 31314.6 Fermentation Processes, Bioreactor Design, and Downstream Processing 31314.7 Applications of Microbial Carotenoids 31414.7.1 Nutraceutical and Pharmaceutical Applications 31414.7.2 Food Coloring and Cosmetic Industry 31514.7.3 Antioxidant Properties and Health Benefits 31514.8 Challenges and Future Perspectives 31514.9 Conclusion 316References 31615 Exploring the Chemistry and Sources of Microbial 1,2- Propanediol [Propylene glycol] with a Focus on Biosynthesis, Extraction, and Identification for Nutraceutical Significance and Human Health 325Alaa Kareem Niamah, Shayma Thyab Gddoa Al- Sahlany, Deepak Kumar Verma, Amit Kumar Singh, Manish Kumar Singh, Rakesh Mohan Shukla, Smita Singh, Ami R. Patel, Gemilang Lara Utama, Mónica L. Chávez González, José Sandoval- Cortés, Prem Prakash Srivastav, and Cristobal Noe Aguilar15.1 Introduction 32515.2 Structure and Chemistry of Microbial 1,2- Propanediol 32715.3 Sources and Synthesis of 1,2- Propanediol 32915.3.1 Sources of Microbial 1,2- Propanediol 32915.3.2 Synthesis of 1,2- Propanediol 32915.3.2.1 Chemical Production 32915.3.2.2 Microbial Production 33115.3.2.3 Deployed Biochemical Pathways for Synthesis 33315.4 Extraction, Identification, and Characterization Process 33415.5 Nutraceutical Importance and Human Health 33815.6 Prospective Future and Research Opportunities 34015.7 Concluding Remarks 342References 34316 Innovations in the Production of Multivitamins in Microbial Factories 349Nupur, Mohit Kumar, Aditi Singh, Neeraj Agarwal, Narendra Kumar, and Santosh Kumar Mishra16.1 Introduction 34916.1.1 Overview and Classification of Multivitamins 35016.1.2 Definition and Need of Microbial Factories 35016.2 Microbial Factories for Multivitamin Production 35016.2.1 Role of Microbial Factories in Vitamin Synthesis 35316.2.2 Advantages of Using Microbial Factories 35316.2.3 Types of Microorganisms Used in Multivitamin Production 35416.3 Innovations in Multivitamin Production 35416.3.1 Genetic Engineering Techniques for Enhanced Vitamin Synthesis 35416.3.2 Optimization of Fermentation Processes 35916.3.3 Novel Approaches for Vitamin Extraction and Purification 35916.3.4 Advances in Encapsulation and Delivery Systems 36016.4 Current Scenario and Future Prospects 360References 36017 An Overview of GABA Production by Microorganisms 365Hend Altaib, Mahmoud A. M. El- Nouby, and Yassien Badr17.1 Introduction 36517.2 Chemical Structure and Biosynthesis of GABA 36617.3 Physiological and Biological Functions of GABA for Microorganisms and Carrier Hosts 36617.3.1 Role in Microorganisms 36617.3.2 Role of Microbial GABA for the Carrier Host 36917.3.3 Role of GABA in Plants 36917.4 Applications for GABA 37017.5 Critical Parameters for Enhanced Microbial GABA Production from Microorganisms 37217.5.1 Optimizing Fermentation Process (Type of Fermentation– Substrate– pH) 37217.5.1.1 The Effect of Media Additives and Fermentation– Substrate 37817.5.1.2 The Effect of pH 37817.5.1.3 Temperature Influence 37917.5.1.4 Cultivation Time Impact 38017.5.2 Methodology of Design of Experiments (DOE) 38017.5.3 Genetic Engineering 38117.5.4 Physiology- oriented Engineering 38217.5.5 Co- culture Engineering 38317.6 Models of Engineered GABA Producer Organisms 38317.6.1 Corynebacterium 38317.6.2 Lab 38417.6.3 Bifidobacterium 38517.6.4 E. coli 38617.7 Conclusion 386Abbreviations 387References 38718 Promising GRAS Strains for Production of Nutraceuticals 399Sanjay Kala, Shashank Singh, Chayanika Kala, and Anurag Singh18.1 Introduction 39918.1.1 Nutraceuticals 39918.1.2 Generally Regarded As Safe (GRAS) Strains 40018.1.3 Lactobacillus Strains 40018.1.4 Bifidobacterium Strains 40118.1.5 Saccharomyces Species 40218.1.6 Bacillus Species 40318.1.7 Streptococcus Species 40418.1.8 Enterococcus faecium 40518.1.9 Propionibacterium freudenreichii 40518.1.10 Clostridium butyricum 40618.1.11 Leuconostoc mesenteroides 40618.1.12 Escherichia coli Nissle 40618.1.13 Torulaspora delbrueckii 40718.1.14 Corynebacterium glutamicum 40718.1.15 Yarrowia lipolytica 40818.2 Conclusion 408Acknowledgment 408Conflict of Interest 409References 40919 Microalgae: A Sustainable Source for Next- Generation Nutraceuticals 413Neha Goel and Poonam Choudhary19.1 Introduction 41319.2 Microalgae: A Source for Nutraceutical Products 41419.2.1 Microalgae and Its Biological Importance 41519.2.2 Nutraceuticals from Microalgae: Types and Significance 42019.2.2.1 Dietary Supplements 42019.2.2.2 Functional and Medicinal Foods 42219.2.2.3 Pharmaceuticals 42419.3 Bioprocess Development of Nutraceutical Products 42919.3.1 Bioprocessing of Microalgal Nutraceuticals 42919.3.2 Downstream Processing Techniques for Product Recovery 43019.3.2.1 Cell Recovery 43019.3.2.2 Cell Disruption 43119.3.2.3 Product Purification 43519.3.2.4 Product Polishing 43619.4 Economics and Market Demand of Nutraceuticals from Microalgae 43619.5 Conclusion 438References 439Index 000