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    Microbial Production of Food Ingredients and Additives
    Microbial Production of Food Ingredients and Additives
    Microbial Production of Food Ingredients and Additives
    Ebook1,129 pages12 hours

    Microbial Production of Food Ingredients and Additives

    By Alexandru Mihai Grumezescu and Alina Maria Holban

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    Microbial Production of Food Ingredients and Additives, Volume Five, the latest release in the Handbook of Food Bioengineering series, is a solid resource on how microorganisms can increase food production and quality. Microorganisms are used to create and enhance food, used as food additives to improve food taste, and in improving function and fortification to benefit overall health. The book presents the applications of microbial products in food bioengineering and methods to obtain valuable ingredients, such as sugars, acids, secondary metabolites, enzymes and vitamins. Recent and future applications of these microbial – derived food components are discussed, along with future applications.

    • Provides various research examples on how microbial production can improve food by lactic acid bacteria
    • Presents information on how microorganisms may be utilized to produce high quantity and quality therapeutic food ingredients used for human and animal food
    • Includes numerous applications to provide a broad perspective on the benefits of microbial production and how they are an alternative to chemical production and purification of ingredients
    LanguageEnglish
    PublisherAcademic Press
    Release dateAug 4, 2017
    ISBN9780128111994
    Microbial Production of Food Ingredients and Additives

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      Book preview

      Microbial Production of Food Ingredients and Additives - Alexandru Mihai Grumezescu

      Microbial Production of Food Ingredients and Additives

      Handbook of Food Bioengineering, Volume 5

      Edited by

      Alina Maria Holban

      Alexandru Mihai Grumezescu

      Table of Contents

      Cover

      Title page

      Copyright

      List of Contributors

      Foreword

      Series Preface

      Preface for Volume 5: Microbial Production of Food Ingredients and Additives

      Chapter 1: Microbial Production of Added-Value Ingredients: State of the Art

      Abstract

      1. Introduction

      2. Microbial Production of Ingredients

      3. Enzymatic Production of Ingredients

      4. Conclusions

      Chapter 2: Phytase as a Diet Ingredient: From Microbial Production to Its Applications in Food and Feed Industry

      Abstract

      1. Phytate

      2. Phytase

      3. Conclusions

      Chapter 3: Current Trends and Future Prospective of Prebiotics as Therapeutic Food

      Abstract

      1. Introduction

      2. The Concept of Prebiotics as Therapeutic Food

      3. Classification of Prebiotics

      4. The Mechanism of Prebiotics

      5. Current Trends and Their Applications

      6. Cutting-Edge Research and Production Methods of Prebiotics

      7. Novel Sources of Prebiotics

      8. Safety Consideration of Prebiotics

      9. Future Perspectives of Prebiotic Research

      10. Conclusions

      Chapter 4: Food Ingredients Synthesized by Lactic Acid Bacteria

      Abstract

      1. Introduction

      2. Exopolysaccharides Produced by LAB

      3. Aroma Compounds Produced by LAB

      4. Polyols

      5. Antimicrobial Compounds

      6. Vitamin Production by LAB

      7. Conclusions and Perspectives

      Acknowledgments

      Chapter 5: Microbial Diversity and Flavor Quality of Fermented Beverages

      Abstract

      1. Fermented Beverages

      2. Microorganisms Involved in Fermented Beverages Production

      3. Volatile Metabolites and Quality of Fermented Beverages

      4. Conclusions and Perspectives

      Chapter 6: Prebiotic and Synbiotic Foods

      Abstract

      1. Characterization of Prebiotics

      2. Probiotics

      3. Application of Prebiotics and Probiotics in Food Products

      4. Conclusions

      Chapter 7: Production, Use, and Prospects of Microbial Food Colorants

      Abstract

      1. Introduction

      2. History of the Use of Food Colorants

      3. Sources of Microbial Food Colorants

      4. Qualities of Good-Food Colorants

      5. Assay of Microbial Colorants

      6. Physiological Basis for Colorant Production in Microorganisms

      7. Mechanisms of Colorant Production in Microorganisms

      8. Genetic and Metabolic Engineering of Colorant Production in Microorganisms

      9. Factors Affecting Growth and Colorant Production in Microorganisms

      10. Production and Downstream Processes

      11. Applications of Microbial Colorants

      12. Market Trends in Microbial Food Colorants

      13. Challenges and Limitations to Microbial Food Colorant Exploitation

      14. Prospects and Challenges

      15. Conclusions

      Acknowledgements

      Chapter 8: Biopolymer Produced by the Lactic Acid Bacteria: Production and Practical Application

      Abstract

      1. Introduction

      2. Background of Lactic Acid Polysaccharides

      3. Production, Isolation, and Purification of EPS

      4. Characterization of EPS

      5. Application of EPS

      6. Future Prospects

      Chapter 9: Microbial Production of Low-Calorie Sugars

      Abstract

      1. Introduction

      2. Erythritol

      3. Mannitol

      4. Xylitol

      5. Tagatose

      6. Psicose

      7. Conclusions

      Chapter 10: Microbial Production of Itaconic Acid

      Abstract

      1. Introduction

      2. Definition and Properties of Itaconic Acid

      3. Historical View

      4. Chemical Route for Itaconic Acid Production

      5. Itaconic Acid Production Through Bioprocesses

      6. Biosynthesis of Itaconic Acid

      7. Food Industry Application

      8. Other Industrial Applications

      9. Industrial Production and Market of Itaconic Acid

      10. Conclusions

      Chapter 11: Microbial Production of Secondary Metabolites as Food Ingredients

      Abstract

      1. Introduction

      2. Bioactive Compounds From Microbial Sources

      3. Antioxidant and Antimicrobial Activity of Microbial Secondary Metabolites

      4. Antibiotic Production From Microorganisms

      5. Anticancer Agents From Microorganisms

      6. Organic Acids From Microorganisms

      7. Bacteriocins

      8. Hydrolytic Enzymes From Microbial Sources

      9. Agrowaste Residues for Secondary Metabolite Production

      10. Strategies to Enhance the Bioproduct

      11. Statistical Approach to Optimize Microbial Bioproducts

      12. Future Aspects

      Chapter 12: Microbial Polysaccharides as Food Ingredients

      Abstract

      1. Introduction

      2. Levan

      3. Pullulan

      4. Xanthan Gum

      5. Curdlan

      6. Gellan

      7. Chitosan

      8. Scleroglucan

      9. Concluding Remarks

      Chapter 13: Xanthan: Biotechnological Production and Applications

      Abstract

      1. Introduction

      2. Structure and Properties

      3. Applications of Xanthan

      4. Biotechnological Production

      5. Industrial Production

      6. Prospects and Challenges

      Acknowledgments

      Chapter 14: Designer Foods: Scope for Enrichment With Microbe-Sourced Antioxidants

      Abstract

      1. Introduction

      2. Global Market for Designer or Functional Food

      3. Free Radicals and the Demand for Antioxidants

      4. Sources of Nonmicrobial Antioxidants

      5. Microbe-Derived Antioxidants

      6. Techniques to Deliver Antioxidants in Foods

      7. Regulatory Issues

      8. Conclusions

      Chapter 15: Monitoring of Microbial Activity in Real-Time

      Abstract

      1. Introduction

      2. Methods in Food Diagnostics

      3. Conclusions

      Index

      Copyright

      Academic Press is an imprint of Elsevier

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      Copyright © 2017 Elsevier Inc. All rights reserved.

      No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

      This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

      Notices

      Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

      Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

      To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

      Library of Congress Cataloging-in-Publication Data

      A catalog record for this book is available from the Library of Congress

      British Library Cataloguing-in-Publication Data

      A catalogue record for this book is available from the British Library

      ISBN: 978-0-12-811520-6

      For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

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      List of Contributors

      Asif Ahmad,     Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan

      Zaheer Ahmed,     Allama Iqbal Open University Islamabad, Islamabad, Pakistan

      Gabriela Alves Macedo,     University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      Gülben Avşar,     Marmara University, Istanbul, Turkey

      Ilona Błaszczyk,     Technical University of Lodz, Institute of Food Technology and Analysis, Lodz, Poland

      Prasandeep Biswal,     Siksha O Anusandhan University, Bhubaneswar, Odisha, India

      Eliana F. Camporese Sérvulo,     Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

      Louise C. Candido da Silva,     Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil

      Hasan B. Coban,     The Pennsylvania State University, University Park, PA, United States

      Juliana C. da Cruz,     Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

      Alok P. Das,     Tripura University (A Central University), Suryamaninagar, Tripura, India

      Aline M. de Castro,     Research and Development Center, Petrobras, Rio de Janeiro, Brazil

      Lívia V. de Castro Reis,     University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      Francisco J. de la Torre-González,     National Polytechnic Institute—Centre for Genomic Biotechnology (Instituto Politécnico Nacional—Centro de Biotecnología Genómica, IPN—CBG), Reynosa, Tamaulipas, Mexico

      Miriam A. de Oliveira Pinto,     Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil

      Ali Demirci,     The Pennsylvania State University, University Park, PA, United States

      Rashmi Dikshit,     Jain University, Bengaluru, Karnataka, India

      Burak Adnan Erkorkmaz,     Marmara University, Istanbul, Turkey

      Marianna M. Furtado,     University of Campinas, Campinas, São Paulo, Brazil

      Pawel Glibowski,     University of Life Sciences in Lublin, Lublin, Poland

      Humberto M. Hungaro,     Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil

      Jan Iciek,     Technical University of Lodz, Institute of Food Technology and Analysis, Lodz, Poland

      Onur Kırtel,     Marmara University, Istanbul, Turkey

      Claudia P. Larralde-Corona,     National Polytechnic Institute—Centre for Genomic Biotechnology (Instituto Politécnico Nacional—Centro de Biotecnología Genómica, IPN—CBG), Reynosa, Tamaulipas, Mexico

      Danielle B. Lopes,     University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      Paloma López,     Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      Karina M. Macena Leão,     University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      José V. Madeira Júnior,     University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      Mª Luz Mohedano,     Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      Magdalena Molska,     Technical University of Lodz, Institute of Food Technology and Analysis, Lodz, Poland

      Montserrat Nácher-Vázquez,     Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      José A. Narváez-Zapata,     National Polytechnic Institute—Centre for Genomic Biotechnology (Instituto Politécnico Nacional—Centro de Biotecnología Genómica, IPN—CBG), Reynosa, Tamaulipas, Mexico

      Uche O. Ogbodo,     University of Nigeria, Nsukka, Enugu State, Nigeria

      Ebru T. Öner,     Marmara University, Istanbul, Turkey

      Abhisek Pal,     Siksha O Anusandhan University, Bhubaneswar, Odisha, India

      Sharadwata Pan,     Indian Institute of Technology Delhi, New Delhi, India

      Ami Patel,     Mansinhbhai Institute of Dairy and Food Technology (MIDFT), Mehsana, Gujarat, India

      Falguni Patra,     Mansinhbhai Institute of Dairy and Food Technology (MIDFT), Mehsana, Gujarat, India

      Adrian Pérez-Ramos,     Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      Mirian P. Rodarte,     Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil

      Indira P. Sarethy,     Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India

      Nihir Shah,     Mansinhbhai Institute of Dairy and Food Technology (MIDFT), Mehsana, Gujarat, India

      Katarzyna Skrzypczak,     University of Life Sciences in Lublin, Lublin, Poland

      Padmavathi Tallapragada,     Jain University, Bengaluru, Karnataka, India

      Brenda N. Targino,     Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil

      Jerry O. Ugwuanyi,     University of Nigeria, Nsukka, Enugu State, Nigeria

      Nuria Vieco

      Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      Polytech’Lille, University of Lille 1, France

      Kenza Zarour

      Center for Biological Research, Higher Council for Scientific Research, Madrid, Spain

      University of Oran 1 Ahmed Ben Bella, Algeria

      Foreword

      In the last 50 years an increasing number of modified and alternative foods have been developed using various tools of science, engineering, and biotechnology. The result is that today most of the available commercial food is somehow modified and improved, and made to look better, taste different, and be commercially attractive. These food products have entered in the domestic first and then the international markets, currently representing a great industry in most countries. Sometimes these products are considered as life-supporting alternatives, neither good nor bad, and sometimes they are just seen as luxury foods. In the context of a permanently growing population, changing climate, and strong anthropological influence, food resources became limited in large parts of the Earth. Obtaining a better and more resistant crop quickly and with improved nutritional value would represent the Holy Grail for the food industry. However, such a crop could pose negative effects on the environment and consumer health, as most of the current approaches involve the use of powerful and broad-spectrum pesticides, genetic engineered plants and animals, or bioelements with unknown and difficult-to-predict effects. Numerous questions have emerged with the introduction of engineered foods, many of them pertaining to their safe use for human consumption and ecosystems, long-term expectations, benefits, challenges associated with their use, and most important, their economic impact.

      The progress made in the food industry by the development of applicative engineering and biotechnologies is impressive and many of the advances are oriented to solve the world food crisis in a constantly increasing population: from genetic engineering to improved preservatives and advanced materials for innovative food quality control and packaging. In the present era, innovative technologies and state-of-the-art research progress has allowed the development of a new and rapidly changing food industry, able to bottom-up all known and accepted facts in the traditional food management. The huge amount of available information, many times is difficult to validate, and the variety of approaches, which could seem overwhelming and lead to misunderstandings, is yet a valuable resource of manipulation for the population as a whole.

      The series entitled Handbook of Food Bioengineering brings together a comprehensive collection of volumes to reveal the most current progress and perspectives in the field of food engineering. The editors have selected the most interesting and intriguing topics, and have dissected them in 20 thematic volumes, allowing readers to find the description of basic processes and also the up-to-date innovations in the field. Although, the series is mainly dedicated to the engineering, research, and biotechnological sectors, a wide audience could benefit from this impressive and updated information on the food industry. This is because of the overall style of the book, outstanding authors of the chapters, numerous illustrations, images, and well-structured chapters, which are easy to understand. Nonetheless, the most novel approaches and technologies could be of a great relevance for researchers and engineers working in the field of bioengineering.

      Current approaches, regulations, safety issues, and the perspective of innovative applications are highlighted and thoroughly dissected in this series. This work comes as a useful tool to understand where we are and where we are heading to in the food industry, while being amazed by the great variety of approaches and innovations, which constantly changes the idea of the food of the future.

      Anton Ficai, PhD (Eng)

      Department Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Bucharest, Romania

      Series Preface

      The food sector represents one of the most important industries in terms of extent, investment, and diversity. In a permanently changing society, dietary needs and preferences are widely variable. Along with offering a great technological support for innovative and appreciated products, the current food industry should also cover the basic needs of an ever-increasing population. In this context, engineering, research, and technology have been combined to offer sustainable solutions in the food industry for a healthy and satisfied population.

      Massive progress is constantly being made in this dynamic field, but most of the recent information remains poorly revealed to the large population. This series emerged out of our need, and that of many others, to bring together the most relevant and innovative available approaches in the amazing field of food bioengineering. In this work we present relevant aspects in a pertinent and easy-to-understand sequence, beginning with the basic aspects of food production and concluding with the most novel technologies and approaches for processing, preservation, and packaging. Hot topics, such as genetically modified foods, food additives, and foodborne diseases, are thoroughly dissected in dedicated volumes, which reveal the newest trends, current products, and applicable regulations.

      While health and well-being are key drivers for the food industry, market forces strive for innovation throughout the complete food chain, including raw material/ingredient sourcing, food processing, quality control of finished products, and packaging. Scientists and industry stakeholders have already identified potential uses of new and highly investigated concepts, such as nanotechnology, in virtually every segment of the food industry, from agriculture (i.e., pesticide production and processing, fertilizer or vaccine delivery, animal and plant pathogen detection, and targeted genetic engineering) to food production and processing (i.e., encapsulation of flavor or odor enhancers, food textural or quality improvement, and new gelation- or viscosity-enhancing agents), food packaging (i.e., pathogen, physicochemical, and mechanical agents sensors; anticounterfeiting devices; UV protection; and the design of stronger, more impermeable polymer films), and nutrient supplements (i.e., nutraceuticals, higher stability and bioavailability of food bioactives, etc.).

      The series entitled Handbook of Food Bioengineering comprises 20 thematic volumes; each volume presenting focused information on a particular topic discussed in 15 chapters each. The volumes and approached topics of this multivolume series are:

      Volume 1: Food Biosynthesis

      Volume 2: Food Bioconversion

      Volume 3: Soft Chemistry and Food Fermentation

      Volume 4: Ingredient Extraction by Physicochemical Methods in Food

      Volume 5: Microbial Production of Food Ingredients and Additives

      Volume 6: Genetically Engineered Foods

      Volume 7: Natural and Artificial Flavoring Agents and Food Dyes

      Volume 8: Therapeutic Foods

      Volume 9: Food Packaging and Preservation

      Volume 10: Microbial Contamination and Food Degradation

      Volume 11: Diet, Microbiome, and Health

      Volume 12: Impacts of Nanoscience on the Food Industry

      Volume 13: Food Quality: Balancing Health and Disease

      Volume 14: Advances in Biotechnology in the Food Industry

      Volume 15: Foodborne Diseases

      Volume 16: Food Control and Biosecurity

      Volume 17: Alternative and Replacement Foods

      Volume 18: Food Processing for Increased Quality and Consumption

      Volume 19: Role of Material Science in Food Bioengineering

      Volume 20: Biopolymers for Food Design

      The series begins with a volume on Food Biosynthesis, which reveals the concept of food production through biological processes and also the main bioelements that could be involved in food processing. The second volume, Food Bioconversion, highlights aspects related to food modification in a biological manner. A key aspect of this volume is represented by waste bioconversion as a supportive approach in the current waste crisis and massive pollution of the planet Earth. In the third volume, Soft Chemistry and Food Fermentation, we aim to discuss several aspects regarding not only to the varieties and impacts of fermentative processes, but also the range of chemical processes that mimic some biological processes in the context of the current and future biofood industry. Volume 4, Ingredient Extraction by Physicochemical Methods in Food, brings the readers into the world of ingredients and the methods that can be applied for their extraction and purification. Both traditional and most of the modern techniques can be found in dedicated chapters of this volume. On the other hand, in volume 5, Microbial Production of Food Ingredients and Additives, biological methods of ingredient production, emphasizing microbial processes, are revealed and discussed. In volume 6, Genetically Engineered Foods, the delicate subject of genetically engineered plants and animals to develop modified foods is thoroughly dissected. Further, in volume 7, Natural and Artificial Flavoring Agents and Food Dyes, another hot topic in food industry—flavoring and dyes—is scientifically commented and valuable examples of natural and artificial compounds are generously offered. Volume 8, Therapeutic Foods, reveals the most utilized and investigated foods with therapeutic values. Moreover, basic and future approaches for traditional and alternative medicine, utilizing medicinal foods, are presented here. In volume 9, Food Packaging and Preservation, the most recent, innovative, and interesting technologies and advances in food packaging, novel preservatives, and preservation methods are presented. On the other hand, important aspects in the field of Microbial Contamination and Food Degradation are presented in volume 10. Highly debated topics in modern society: Diet, Microbiome, and Health are significantly discussed in volume 11. Volume 12 highlights the Impacts of Nanoscience on the Food Industry, presenting the most recent advances in the field of applicative nanotechnology with great impacts on the food industry. Additionally, volume 13 entitled Food Quality: Balancing Health and Disease reveals the current knowledge and concerns regarding the influence of food quality on the overall health of population and potential food-related diseases. In volume 14, Advances in Biotechnology in the Food Industry, up-to-date information regarding the progress of biotechnology in the construction of the future food industry is revealed. Improved technologies, new concepts, and perspectives are highlighted in this work. The topic of Foodborne Diseases is also well documented within this series in volume 15. Moreover, Food Control and Biosecurity aspects, as well as current regulations and food safety concerns are discussed in the volume 16. In volume 17, Alternative and Replacement Foods, another broad-interest concept is reviewed. The use and research of traditional food alternatives currently gain increasing terrain and this quick emerging trend has a significant impact on the food industry. Another related hot topic, Food Processing for Increased Quality and Consumption, is considered in volume 18. The final two volumes rely on the massive progress made in material science and the great applicative impacts of this progress on the food industry. Volume 19, Role of Material Science in Food Bioengineering, offers a perspective and a scientific introduction in the science of engineered materials, with important applications in food research and technology. Finally, in the volume 20, Biopolymers for Food Design, we discuss the advantages and challenges related to the development of improved and smart biopolymers for the food industry.

      All 20 volumes of this comprehensive collection were carefully composed not only to offer basic knowledge for facilitating understanding of nonspecialist readers, but also to offer valuable information regarding the newest trends and advances in food engineering, which is useful for researchers and specialized readers. Each volume could be treated individually as a useful source of knowledge for a particular topic in the extensive field of food engineering or as a dedicated and explicit part of the whole series.

      This series is primarily dedicated to scientists, academicians, engineers, industrial representatives, innovative technology representatives, medical doctors, and also to any nonspecialist reader willing to learn about the recent innovations and future perspectives in the dynamic field of food bioengineering.

      Alina M. Holban

      University of Bucharest, Bucharest, Romania

      Alexandru M. Grumezescu

      Politehnica University of Bucharest, Bucharest, Romania

      Preface for Volume 5: Microbial Production of Food Ingredients and Additives

      Microorganisms possess an impressive role in supporting life and ecology. These microscopic individuals may work as separate entities or multicellular specialized consortia, named biofilms, to produce numerous useful molecules. Their impact in natural processes and also current industry is so important, that life on Earth as we know it today is only possible due to the activities of microorganisms. Numerous industries have exploited the biochemical ability of microbes to synthesize, metabolize, and transform valuable substances. These properties of microorganisms support chemical industries, biotechnology, pharmaceutical industry, and nonetheless, food industry.

      Most of the available food ingredients, food nutraceuticals, additives, colorants, and flavoring agents are produced by or with the help of microorganisms. Classical processes, which support current biotechnology and food industry, such as fermentation and enzyme production are exclusively based on microbial activities. They represent a resourceful source of food-related products and are responsible for many of the properties and taste of dairy products, which we daily consume.

      The aim of this book was to bring together the most recent progress achieved in the field of microbial production of food-related products and additives, emphasizing the current progress, actual concerns in the biotechnological field, and success of very recent technologies. This volume introduces the reader in the amazing world of industrial microbiology and highlights the recent progress made in the field of microbial food industry. An overview regarding where we are situated in terms of microbial food synthesis and where we are heading to, can be also exploited within this book.

      The volume contains 15 chapters prepared by outstanding authors from Brazil, USA, India, Spain, France, Mexico, Poland, Nigeria, Pakistan, and Turkey.

      The selected manuscripts are clearly illustrated and contain accessible information for a wide audience, especially food scientists, engineers, biotechnologists, biochemists, industrial companies and also for any reader interested in learning about the most interesting and recent advances in the field of microbial production of food ingredients and additives.

      Chapter 1, entitled Microbial Production of Added-Value Ingredients: State of Art, written by Lopes et al., describes relevant aspects of the microbial production of various ingredients, such as flavors, esters, and vitamins, and their enzymes used in food and pharmaceutical industries.

      Chapter 2, Phytase as a Diet Ingredient: From Microbial Production to Its Applications in Food and Feed Industry, prepared by Coban and Demirci, provides an extensive review about microbial phytase production, characteristics of phytase, various phytase fermentation systems, as well as its application in food and feed industry.

      In Chapter 3, Current Trends and Future Prospective of Prebiotics as Therapeutic Food, Biswal et al. debate the current trends and future prospects of prebiotics as therapeutic food, epitomizing cutting-edge research outcomes on prebiotic, novel sources, and their application in human health.

      In Chapter 4, Food Ingredients Synthesized by Lactic Acid Bacteria, Zarour et al. give an overview regarding the current status of food products obtained with the help of lactic acid bacteria (LAB). The in situ production of vitamins, as well as the use of polyols synthesized by these bacteria as low-calorie sweeteners, is discussed. The dual roles of LAB exopolysaccharides to improve food texture and as component of functional food are also described, as is the contribution to the flavor of fermented food products by aroma compounds generated from citrate metabolism and amino acids catabolism by LAB. Finally, the use of LAB bacteriocins, synthesized in situ, or as additives, for food preservation is presented in this chapter.

      In Chapter 5, Microbial Diversity and Flavor Quality of Fermented Beverages, De La Torre-González et al. revealed the main production processes and the organoleptic characteristics of the most widely consumed fermented beverages in the world, including wine and tequila, and the impact of microorganisms that are used as inoculants in the aroma and quality of these beverages.

      Chapter 6, Prebiotic and Synbiotic Foods, written by Glibowski and Skrzypczak, discusses recent studies concerning the foods in which prebiotic substances, as well as probiotic bacteria were applied. There are many studies describing application of various prebiotics (i.e., galactooligosaccharides, soy oligosaccharides, xylooligosaccharides, pyrodextrins, isomaltooligosaccharides, or lactulose) but the most frequently investigated are fructans—inulin, fructooligosaccharides, and oligofructose. This chapter highlights that symbiotic food, which contain prebiotics and probiotics can be an alternative to traditional foods and this food can positively impact health and can prevent from severe diseases.

      In Chapter 7, Production, Use, and Prospects of Microbial Food Colorants, Ogbodo and Ugwuanyi aim at exploring and discussing the current production protocols, as well as the prospects and challenges faced by the industry of colorants obtained through microbial activity.

      Chapter 8, Biopolymer Produced by the lactic Acid Bacteria: Production and Practical Application, written by Ahmed and Ahmad, summarizes the production, isolation, and recent characterization approaches for bacteria produced biopolymers, and also their application in health, food additives, food engineering, and nanotechnology.

      In Chapter 9, Microbial Production of Low-Calorie Sugars, Patra et al. describe the microbial production of low-calorie sweeteners, which can be categorized into two groups; intense sweetener, such as neotame, acesulfame-K, aspartame, saccharin, sucralose, etc. and naturally occurring reduced calorie bulk sweeteners, for example, erythritol, mannitol, xylitol, sorbitol, isomalt, lactitol, trehalose, hydrogenated starch hydrolysates, hydrogenated glucose syrups, etc. Besides foods, these sugars are widely used in pharmaceutical, medicine, and chemical industries.

      In Chapter 10, Microbial Production of Itaconic Acid, prepared by da Cruz et al., dissected the industrial production of itaconic acid (IA), which is mainly done by Aspergillus terreus. However, other microorganisms are capable of producing this acid, some of them genetically modified. The exact regulation of IA synthesis is unknown and it is investigated by means of studies of media composition, pH, O2 supply, temperature, presence, or absence of trace elements during fermentation. Recent records indicate that the global market for IA will grow to US $398.3 million in 2017, indicating a great interest in improving IA production.

      Chapter 11, Microbial Production of Secondary Metabolites as Food Ingredients, written by Tallapragada and Dikshit, explores the usage of microorganism for the biosynthesis of natural products, such as lovastatin, gama amino butyric acid, etc. and also food coloring, antimicrobial, and anticancer agents. Production of enzymes, such as beta-glucosidase, amylases, organic acids, probiotic cells, and bacteriocins for their usage in foods, nutraceuticals, and medications are also discussed. Additionally, the chapter discusses the challenges associated with the production of these bioproducts and their scaled up production for industrial purpose.

      In Chapter 12, Microbial Polysaccharides as Food Ingredients, Kırtel et al. describe the chemical structure, general properties, production strategies, food applications, and future trends of the most widely used microbial polysaccharides, namely curdlan, gellan, levan, pullulan, and xanthan. The chapter also covers cost-effective production techniques for these valuable biopolymers.

      In Chapter 13, Xanthan: Biotechnological Production and Applications, Candido da Silva et al. give a general overview of xanthan, including its applications, biotechnological production, and challenges. Xanthan is an exopolysaccharide obtained from a fermentation process using bacteria of the genus Xanthomonas. The rheological properties and stability in a wide range of temperatures and pH make this biopolymer one of the most important commercial ingredients produced by microorganisms.

      In Chapter 14, Designer Foods: Scope for Enrichment With Microbe-Sourced Antioxidants, written by Sarethy and Pan, focuses on the antioxidants produces by microorganisms, the wide diversity that have been studied, their mode of action, feasibility of adding such microbe-derived antioxidants in conventional foods and the associated regulatory issues.

      Chapter 15, entitled Monitoring of Microbial Activity in Real-Time, written by Iciek et al., reveals the methods of detection and identification of microorganisms, with emphasis on the use of redox potential measurement for the individual control of food production processes in various models.

      Alina M. Holban

      University of Bucharest, Bucharest, Romania

      Alexandru M. Grumezescu

      Politehnica University of Bucharest, Bucharest, Romania

      Chapter 1

      Microbial Production of Added-Value Ingredients: State of the Art

      Danielle B. Lopes

      José V. Madeira Júnior

      Lívia V. de Castro Reis

      Karina M. Macena Leão

      Gabriela Alves Macedo    University of Campinas (UNICAMP), Campinas-SP, São Paulo, Brazil

      Abstract

      Microbial production is considered as a potential process for the biosynthesis of several natural ingredients, such as flavors, esters, vitamins, phenolic compounds, and so on; fungi are the most widely used for this purpose. Advances in microbial enzyme technology offer considerable opportunities for the development of energy-saving technologies for the bioconversion of added-value products. Biocatalysis is also an advantageous alternative to catalyze a number of regio- and stereoselective reactions, which is not achieved by classical chemical synthesis. The use of isolated enzymes becomes preferred to the use of microorganisms when there are limitations concerning the permeability of the substrate into the cell or if undesired side reactions occur. In this chapter we describe some relevant aspects of the production of various ingredients, such as flavors, esters, vitamins, and so on, by microorganisms and their enzymes used in food and pharmaceutical industries.

      Keywords

      biotechnology

      microbial production

      enzyme

      biocatalysis

      biotransformation

      value-added ingredient

      flavor

      ester

      nutraceutical

      1. Introduction

      Microorganisms and their enzymes have been used for the scale-up production of a diverse number of biochemicals (e.g., alcohols, esters, antibiotics, and nutraceuticals) and in the processing of feeds and foods (Fig.1.1). The application of microbes to obtain a product or service of economic importance is called microbial biotechnology or bioprocesses (Abdel-Aziz, 2014). These are defined as a reaction or a set of simultaneous reactions in which a preformed molecule precursor is converted to an interesting economic value product, such as vitamins, flavors, and nucleotides (Sanchez and Demain, 2014). The process should comprise the use of whole cells or enzymes (or combinations thereof) either free or immobilized, and should lead to the production of a fine-chemical or commodity product that can be recovered after the reaction (Straathof et al., 2002). Biotransformation and biocatalysis are bioprocesses characterized by the bioconversion of metabolites (Shaw et al., 2003); in the former, whole cells from microorganisms are used; in the later, isolated enzymes from vegetables, animals, or microorganisms are employed. Biocatalysis is an important tool in organic synthesis, particularly in the production of chiral molecules, which cannot be generated through chemical synthesis (Barreiro and Fraga, 2008).

      Figure 1.1   Schematic Bioprocesses for the Production of Value-Added Ingredients.

      The use of natural biocatalysts is secular, and both chemistry and biochemistry traveled a long way together; however, in the early 20th century they became independent sciences (Roberts et al., 1995). The utilization of enzymes and microorganisms in organic chemistry progressed relatively slowly until the 1950s; however, since then the exploration of microbial diversity and function has greatly enhanced (Coyotzi et al., 2016; Shaw et al., 2003). Both bioprocesses use current knowledge about live systems to develop new biological agents that can function as biofactories of value-added products (King et al., 2016; Nikel et al., 2016). These bioprocesses have become standard technologies in the fine chemicals industry, and biocatalysts is now more readily accessible at a lower cost. The major advantages for the application of these bioprocesses in chemical syntheses include their efficiency in performing numerous high-complexity chemical reactions, as well as their broad spectrum of substrates (e.g., agroindustrial by-products), and their mild and environment-friendly conditions (Babson et al., 2014; Mamma and Christakopoulos, 2014).

      Selection of microorganisms, plants, or animal cells and their performance evaluation represent traditional methods for the discovery of new biocatalysts. Microorganisms hold the greatest industrial interest since they have a short generation time and harbor a wide variety of enzymes and metabolic processes. In addition, there is a great diversity of microorganisms throughout nature that can be tested for modifying and degrading a range of complex organic molecules (Conti et al., 2001).

      The number of bioprocesses that are being executed on an industrial scale have grown rapidly. For this reason, and considering these arguments, this chapter reviews developments regarding processes and products that employ microorganisms or enzymes to produce value-added ingredients.

      2. Microbial Production of Ingredients

      Advantages of producing ingredients via chemical approaches include the use of a well-established production platform and low costs; however, this method has severe drawbacks, such as the use of toxic and expensive catalysts, the use of high temperature and pressure, high-energy inputs, the generation of toxic intermediates, and the difficulties in producing stereospecific chemicals (Lee et al., 2012). In comparison, microbial production is now recognized as an industry-applicable technology and has developed into an increasingly viable economical alternative for the production of numerous value-added ingredients (Bozell and Petersen, 2010; Sun et al., 2015). These achievements have become feasible due to increased understanding of the metabolism and routes of regulation of industrially relevant organisms. However, metabolic engineering methods frequently represent predetermined applications for one specific product and are not appropriate for other applications. Most products obtained by microbial production (native or not) are derived from central metabolites; therefore engineering the central metabolism pathway becomes very attractive, not just for a determined product, but additionally for a complete class of products derived from the given central metabolite (Eikmanns and Blombach, 2014).

      Microorganisms (prokaryotic or eukaryotic) possessing a fast growth rate and a simple genetic background are commonly used as hosts to generate innumerable compounds. This strategy suits both metabolic logic, as well as industrial economic scale processes. Many microbial strains, such as Escherichia coli, Saccharomyces cerevisiae, Lactobacillus spp., and so on, are widely used for the production of these valuable ingredients. Other nonconventional hosts have also been explored for their distinctiveness and future large-scale use (Sun et al., 2015) and are described hereafter.

      2.1. Flavors

      The popularity of natural products has triggered significant research activity in the production of flavor compounds using biocatalysts (Schrader et al., 2004). The tendency of consumers to choose natural flavors rather than chemosynthetic ones prompted researchers to discover new methods to produce natural aromas. From a scientific and technological point of view, this field is highly exciting since it brings together several different branches of science (Lopes et al., 2016b; Macedo et al., 2010; Romero-Guido et al., 2011). In American and European regulations, natural is legally defined as a substance that has a plant, animal, or microbial origin or that is produced by a physical, microbial, or enzymatic process. Therefore biotechnological routes may be a way to obtain natural products if they exclude any chemical steps (Romero-Guido et al., 2011).

      Flavor production by microbial processing is gaining attention and support from several food agencies, especially in the United States and Europe. Considering microbial metabolism, sugars and amino acids have been considered the two most important initiators for a desired flavor compound (Etschmann et al., 2002). In addition, identifying one microorganism capable of producing a specific flavor molecule is also gaining attention in the scientific community. These strains can be developed by molecular tools or through selection of a wild strain that comes from an environment suitable for production of the given compound (i.e., yeasts from grape residues in the wine plant industries) (Etschmann et al., 2002; Gombert et al., 2016; Morrissey et al., 2015).

      In this section the most important flavor compounds will be discussed, including their strain producers, mode of cultivation, and yield or productivity. Based on knowledge of the pathways involved in flavor synthesis, metabolic strategies, including engineered strains must be designed to improve production.

      2.1.1. Diacetyl

      Diacetyl has been used in most dairy industry products to increase acceptance because of its buttery flavor. Lactic acid bacteria usually produces diacetyl by citric acid metabolism; however, diacetyl metabolism is not fully understood and there are often difficulties during the manufacture of dairy products (Hugenholtz et al., 2000). Besides diacetyl producing the desired flavor in butter, buttermilk, and cheeses, it is also an important off-flavor in the wine and brewing industries. During fermentation, some microorganisms react with pyruvate to produce α-acetolactate, which is then oxidized to diacetyl (Hugenholtz et al., 2000). In the past 5 years, 6880 papers have been published on diacetyl production, highlighting its importance. Table 1.1 shows the most cited papers on diacetyl production by microbial cultivation and as can be seen, diacetyl production was up- or downregulated based on the medium, pH, temperature, cofactors, and species.

      Table 1.1

      Diacetyl synthesis by microbial cultivation.

      According to Christensen and Pederson (1958), citric acid has been poorly utilized as a carbon source for growth; however, diacetyl synthesis has stimulated this. Heterofermentative bacteria may develop better diacetyl production than homofermentative, although the reason for this is still not fully understood. Hugenholtz et al. (2000) published an engineered Lactococcus lactis for the conversion of sugar into diacetyl. According to the results, 80% of the carbon source was from NADH-oxidase (NOX) overexpression and α-acetolactate decarboxylase (ALDB) inactivation. The NOX enzyme has been used to reduce intracellular NADH to NAD+ and to force the microorganism to produce acetoin or acetyl by the NAD+-dependent pyruvate dehydrogenase complex. However, the ALDB enzyme was inactivated and only turned into diacetyl under the presence of oxygen. Taking all these information into account, aerobic microbial cultivation must be performed to enhance flavor production.

      2.1.2. Lactones

      Lactones are cyclic compounds that have intramolecular ester bonds and belong to an important flavor class (Adams et al., 1998; Vernin and Vernin, 1982). They are widely distributed in nature and play important roles in organisms due to their antifungal (Wedge et al., 2000), antitumor (Saroglou et al., 2010), antimicrobial (Neerman, 2003), and insecticidal (Szczepanic et al., 2016) activities. They can also be metabolic intermediates; be responsible for the odor of flowers and the odor and taste of fruits and vegetables (Adams et al., 1998; Kitaura et al., 2004); be present in foods, such as cheese, bread, and butter (Alewijn et al., 2007; Peterson and Reineccius, 2003); and alcoholic beverages, such as wine, sherry, and whisky (Moreno et al., 2005). Lactones are also pheromones in the insect world, but some isolated from plants and synthetic ones have good antifeedant activity against them (Grudniewska et al., 2013; Mazur et al., 2013). For many of these substances, a stereocenter is found creating enantiomers with different olfactory properties (Hwang et al., 2000).

      As with diacetyl, lactones have been used to add flavor to several dairy products, such as cream and butter (Wikandari et al., 2015). Biotechnological synthesis of lactone was firstly published in 1960s by the Okui group (Okui et al., 1963). Nowadays, the production of lactone through microbial transformation is increasing because of the difficulty in obtaining lactone from plants, and the environmental services stating that the extraction process is no longer desired. The main microbial pathways to obtain lactone are β-oxidation, which involves the use of microorganisms that are able to produce extracellular lipases to hydrolyze fatty acids, and lactonization. Several studies have used coproducts (i.e., castor oil from Ricinus communis) from biofuel industries, which can decrease the amount of undesired products in the world. However, several hydroxy acids can be released from those coproducts, which necessitates the use of a robust strain able to hydrolyze C12, C14, and C16 hydroxy acids. Different hydroxy acids (i.e., decalactone) can be used to accurate fruity and oily flavors (Waché et al., 2003). Table 1.2 shows the most cited papers regarding microbial cultivation of lactones. One the most commonly used strains for biotransformation is the yeast Yarrowia lipolytica, which presents adapted hydrophobic environments and well understood pathways. Genetic tools adapted from S. cerevisiae, in others words, that species can be metabolically engineered and increase production of a desired compound (Waché et al., 2003). According to Bouchez-Naitali et al. (2001), one important issue must be solving upscaling of fatty acids into the cell. The mechanism is not entirely clear but a surfactant-facilitated transport was presented. Lactone concentration was studied decades ago, and cell viability decreases dramatically at 100 and 150 mg/L in bacteria and yeast, respectively (Nago et al., 1993). The reason is dissipation of membrane potential, which is caused by interaction of hydrophobic lactone with the membrane.

      Table 1.2

      Lactone synthesis by microbial cultivation.

      2.1.3. Esters

      Ethyl acetate, hexyl acetate, isoamyl acetate, and 2-phenylethyl acetate are described as the most important esters for adding flavor in foods and beverages. Several products have been improved using these compounds, such as candies, jellies, jams, cheeses, wine, and other grape-derived alcoholic beverages. Their wide spectrum of use is down to their appreciated fruity aromas. The different tastes are formed by different size and structure molecules; structures have been catalyzed by esterases and lipases, which can release different size of molecules and therefore different types of flavor. Lactic acid bacteria and yeasts have been reported for these compounds. Table 1.3 shows the most cited papers regarding microbial cultivation of esters.

      Table 1.3

      Ester synthesis by microbial cultivation.

      According to Rojas et al. (2001), S. cerevisiae produce lower amounts of ester than non-Saccharomyces yeasts under aerobiosis. One possible reason is the nature of the S. cerevisiae, which suffered a historic event called whole-genome duplication that made it metabolize sugars by the fermentative pathway even in the presence of oxygen. Under aerobiosis and low sugar concentrations, this strain catabolizes sugar toward respiratory metabolism, which is itself fluxed highly to biomass and lowly to other products, such as alcohol and esters. Most yeast strains do not present this feature, which means these strains are able to produce higher concentrations of ester than S. cerevisiae.

      Saerens et al. (2008) stated that fermentation conditions can be improved to produce higher ethyl ester. One important component is the high-gravity cultivation, which affects the expression of ester biosynthesis genes. Beside high gravity (high amount of sugar), the temperature of cultivation also triggers the expression of medium-chain fatty acid metabolism, which helps with overproduction of esters. The reason for the expression of these genes is still not fully understood, and further experiments must be performed.

      2.1.4. Organic acids

      Organic acids, alongside other aroma compounds, are responsible for strongly effecting bread flavor and related products. According to the literature, some microorganisms can synthesize organic acids from wheat flour, which increases the acceptable flavor even further (Spicher, 1983). This process could be more interesting than chemical processes since some aspects of fermentation must be followed (i.e., temperature, dough yield, and flour type) (Rothe and Ruttloff, 1983). Strains able to produce organic acids have been identified by acidogenesis metabolism. This process is realized by anaerobic metabolism whereby organic substrates (e.g., volatile fatty acids) are the electron donors and carrying compounds (e.g., NAD+) are responsible for accepting electrons. Several products can be produced from this pathway including organic acids (Finogenova et al., 2005; Magnuson and Lasure, 2004). One of the microorganisms most reported to produce organic acids is the yeast Y. lipolytica. This species is able to uptake and metabolize fatty acids from several sources especially subproducts sources, such as in biodiesel industry (Finogenova et al., 2005).

      2.1.5. Alcohols

      Differently from ethanol, long-chain alcohols are simultaneously produced by glycolysis, pentose phosphate, and ehrlich pathways. However, these complex compounds also react with radical groups by esterification and decarboxylation reactions, which increase their organoleptic properties (Etschmann et al., 2002; Morrissey et al., 2015). In other words, three catabolic processes and anabolic process are performed sequentially to synthesize these flavor compounds (i.e., 2-phenylethanol, 2-methylpropanol, 2-ethylhexanol, etc.). Scientific studies have discussed coculture fermentation to enhance flavor production using bacteria and non-Saccharomyces yeasts (Martin et al., 2001). Table 1.4 shows the most cited papers regarding the production of structured alcohols using microbial cultivation. No studies have shown a clear mechanism for enhancing flavor production under consortium cultivation.

      Table 1.4

      Complexed alcohol synthesis by microbial cultivation.

      One of the main reason to require non-Saccharomyces yeasts to synthesis these compounds is the crabtree effect. Except for S. cerevisiae, most yeast catabolize sugar using respiratory pathways and the intermediate metabolites go toward different pathways, such as 2-phenylethanol production; glucose is oxidized to pyruvate (glycolysis) and then synthetized with amino acid turnover to obtain a fusel alcohol (Morrissey et al., 2015). One interesting species able to produce a wide range of these compounds is the emerging Kluyveromyces marxianus, which presents a great biotechnology potential. This yeast was discovered in 1888, but only in the last 15 years has it been studied more often and become the subject of metabolic engineering strategies (Gombert et al., 2016; Lane and Morrissey, 2010). The physiological characteristics of K. marxianus that distinguish it from other yeasts are: a high specific growth rate (around 1.0 h–1, which is the highest rate ever reported for a eukaryote), an ability to assimilate a wide range of sugars (including inulin and lactose), a high excretion and secretion rate of compounds, high thermotolerance [according to Banat et al. (1992), some K. marxianus strains can grow at 52°C], and a relatively easy genetic manipulation (using protocols adapted from S. cerevisiae and Kluyveromyces lactis) (Fonseca et al., 2007; Groeneveld et al., 2009; Lane and Morrissey, 2010). An important characteristic of K. marxianus is the fact that it is a preferentially respiring yeast. Thus contrary to S. cerevisiae, K. marxianus will rely on respiratory metabolism whenever oxygen is available at nonlimiting concentrations (i.e., it does not depend on the sugar concentration) (Bellaver et al., 2004; Fonseca et al., 2007; Lane and Morrissey, 2010). It is this characteristic that turns a species capable of producing ATP toward respiring metabolism, which facilities the production of flavors.

      To enhance flavor production some issues must be solved. One of the most important facts is the metabolism shift of these strains; some of them present fermentative preference, which avoids the synthesis of undesired compounds. Hence cultivation under aerobiosis or evolved strain can be used; however, the former can increase the cost of production in the industrial scale-up. A new molecular biology tool has been discovered that can solve most of difficulties encountered when engineering a strain for aroma compound synthesis. This tool is called clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), and it allows the simultaneous integration and deletion of multiple genes, which is a powerful tool for flavor production (Mans et al., 2015). In addition, genes that are predicted to confer relevant traits (i.e., biomass production, increased sugar uptake, and increased tolerance) can be tested through introduction into sensitive host strains. Once the functional relevance of specific genes is confirmed, they will be placed under the control of strong promoters and reintroduced into the genome to further boost the phenotype of the selected strain (Mans et al., 2015).

      2.2. Nutraceuticals

      The term nutraceutical is a combination of nutrition and pharmaceutical, and was formerly defined as a substance that was food or a part of food that provided health or medical benefits, including disease prevention and treatment (DeFelice, 1995). This description has been reformulated and, nowadays, nutraceuticals are more specific to various functionally and structurally bioactive compounds that exert long-dated physiological or medicinal benefits. These benefits go further than merely nutritional or direct pharmaceutical effects, which distinguishes them from drugs and functional foods. These compounds can be derived from animals (e.g., polysaccharides), from plants (e.g., vitamins, carotenoids, and phytochemicals), from marine sources (e.g., chitosan and glucosamine), and from microorganisms (e.g., amino acids and polysaccaharides). Nutraceuticals are widely used for their health-promoting or disease-preventing properties, and are especially important in preventing aging-associated diseases, such as depression, oxidative stress, osteoporosis, inflammation, arthritis, cardiovascular and gastrointestinal diseases, cancer, and diabetes (Jain and Ramawat, 2013; Wang et al., 2016a).

      The growing interest in conserving human health through dietary interventions has significantly encouraged progression of the nutraceutical market (Jain and Ramawat, 2013). However, this emerging market can scarcely be fulfilled by the productivity of conventional nutraceutical industries. The straight extraction strategies are restricted by the low yield and purity of nutraceuticals, the insufficient availability and cost of raw materials, and the quality control of supplies. Chemical synthesis is an alternative approach; however, it is limited to the production of simple biochemicals, is impracticable for complex molecules including enantiomers or those that are chemically unfavorable, and is not considered an environment-friendly method as it generates pollution (De Luca et al., 2012; Liu et al., 2015). For these reasons, chemical synthesis methods are being replaced by microbial biotransformation, which has advanced to produce value-added nutraceuticals in recent years (Liu et al., 2015; Ratledge, 2013; Song et al., 2014; Sun et al., 2015). The rapid elucidation of biosynthetic pathways for natural products and the genetic amenability of microorganisms have allowed the development of microbial hosts for production of innumerable nutraceuticals. By further genetic manipulation of host cells and optimization of the culture conditions or fermentation processes, metabolic engineering makes it possible to scale-up the production of nutraceuticals from simple carbon sources (Wang et al., 2016a). Many microbial strains that are generally regarded as safe have been identified and developed for the synthesis of nutraceuticals, and significant production by these strains has been achieved (Liu et al., 2015).

      2.2.1. Vitamins

      Vitamins are defined as essential micronutrients, normally found as precursors of enzymes, which are necessary for vital biochemical reactions in all living cells. They are produced by microorganisms and plants; however, humans are incapable of synthesizing most vitamins and they consequently have to obtain them exogenously. Vitamins belong to a chemically heterogeneous group of organic compounds that are essential for metabolism and for fulfilling catalytic or hormone-like functions in all living organisms. A small daily dietary intake satisfies the requirements for human health (Berstenhorst et al., 2009; LeBlanc et al., 2013; Shimizu, 2001).

      Microorganisms have the ability to synthesize vitamins; in fact, bacteria of the human gut microbiota can produce some vitamins, which if suitably absorbed, can partially meet the organism’s requirements. Following the administration of strong antibiotics (which kill bacteria in the gut), it is suggested that supplementary vitamins be ingested. Microbes can be effectively employed for the commercial production of several vitamins, such as riboflavin, thiamine, biotin, pyridoxine, folic acid, β-carotene (provitamin A), pantothenic acid, ergosterol (provitamin D), and ascorbic acid. Most vitamins and related compounds are now industrially produced and widely used as food or feed additives, medical or therapeutic agents, health aids, cosmetic and technical aids, and so on. Thus vitamins are important products for which many biotechnological production processes, such as fermentation and microbial and enzymatic transformation, have been reported (Ahmed et al., 2014; Ledesma-Amaro et al., 2013; Shimizu, 2001).

      Riboflavin or vitamin B2 is a dietary necessity for humans as, unlike many plants, fungi, and bacteria, they are unable to synthesize the vitamin. Two sources of riboflavin are available to humans: a dietary source and riboflavin produced by microflora of the large intestine (Hill, 1997; Powers, 2003). This vitamin plays an essential role in cellular metabolism and it is the precursor of flavin adenine dinucleotide and flavin mononucleotide coenzymes, both of which act as hydrogen carriers in many biological redox reactions (Massey, 2000). Microbial riboflavin biosynthesis from its precursors (guanosine triphosphate and d-ribulose 5-phosphate) occurs through seven enzymatic steps, with detailed studies performed for Bacillus subtilis (Perkins and Pero, 2002) and E. coli (Bacher et al., 1996, 2001).

      Numerous biotechnological methods have been developed as alternatives to the more expensive chemical synthesis (Hümbelin et al., 1999; Stahmann et al., 2000). In addition to the economic advantage, benefits of the biotechnological approach include the ability to use renewable sources, the reduction in environmental pollution, and the ability to yield a product with equivalent or higher quality (Burgess et al., 2009; van Loon et al., 1996). A wide range of fungi and bacteria have been shown to be able to overproduce riboflavin and this capacity has been exploited for industrial production. The most common commercial producers are Ashbya gossypii and the ascomycetes Eremothecium ashbyii; however, two other microorganisms, B. subtilis and Candida famata, have also been harnessed to produce this vitamin with yields reaching 14 and 20 gL-1, respectively (Perkins et al., 1999; Schallmey et al., 2004; Stahmann et al., 2000).

      The use of metabolic engineering to improve A. gossypii enabled an almost 10-fold increase in the production of riboflavin, as described in the study of Jimenez et al. (2005). This same microorganism was used by Park et al. (2007) to overproduce riboflavin using oil waste. Using mutagenized A. gossypii spores, exposed to UV light and a mutant ZP4 strain, they were able to obtain a threefold increase in riboflavin compared to the wildtype strain.

      With the use of B. subtilis, high levels of riboflavin production were reached as a result of the use of genetic engineering and exposure to analog of purine and the toxic riboflavin analog roseoflavin (Perkins and Pero, 2002; Perkins et al., 1991;  1999). In the case of L. lactis both of these approaches have been used with success (Burgess et al., 2004), and studies from LeBlanc et al. (2005a,b) verified that riboflavin overproduced by strains of this microorganism can be used to reverse riboflavin deficiency in rats. The toxic analog method has also been efficaciously used in the Lactobacillus plantarum, Leuconostoc mesenteroides, and Propionibacterium freudenreichii strains (Burgess et al., 2006), and a dairy product made by fermentation with P. freudenreichii was shown to neutralize the deficiency of riboflavin in an animal model (LeBlanc et al., 2006).

      Vitamin B6 is a group comprising six B6 vitamers (chemical substances that fulfill the same specific vitamin function): pyridoxine, pyridoxamine, pyridoxal, and their respective esters, pyridoxine 5′phosphate, pyridoxamine 5′phosphate, and pyridoxal 5′phosphate. Pyridoxamine 5′phosphate and pyridoxal 5′phosphate are the two biologically active compounds that function as cofactors for a diverse range of metabolic enzymes (Percudani and Peracchi, 2009; Romo and Liu, 2011; Rosenberg, 2012). Moreover, the DNA-binding activities of many transcription factors are modulated by pyridoxal 5′phosphate (Belitsky, 2014; Edayathumangalam et al., 2013; El Qaidi et al., 2013). In addition, vitamin B6 was shown to be involved in the protection of plants and fungi against harmful oxygen species (Moccand et al., 2014). Hence vitamin B6 is involved in numerous cellular functions in both eukaryotes and prokaryotes (Mooney et al., 2009).

      Commichau et al. (2015) studied the ability of B. subtilis to convert the antimetabolite 4-hydroxy-l-threonine to the B6 vitamer pyridoxine, which is the most commonly supplemented B6 vitamer for animals and humans. They developed B. subtilis mutants that were able to tolerate high amounts of the antimetabolite, with the adapted bacteria producing 28–34 mgL-1 of pyridoxine while the wildtype parent produced only 12 mgL-1. This research revealed that the B. subtilis genome is flexible with respect to adaptive mutations, an essential feature for strain engineering.

      Vitamin B12, also called cobalamin, refers to a group of physiologically active cobalt-containing molecules. This compound possesses a large structural complex containing a ring-contracted porphinoid resulting from uroporphyrinogen III with a cobalt ion connected at the center (Randaccio et al., 2010). In humans only two metabolic reactions are dependent on cobalamin, and in both cases cobalamin is used as an indispensable cofactor for the enzymes. The first is a mutase reaction converting L-methylmalonyl-CoA to succinyl-CoA during the assimilation of odd numbered fatty acids. The second is the methionine synthase reaction during which a methyl group is transferred from methyltetrahydrofolate to homocysteine to form methionine (Cheng et al., 2014; Takahashi-Iñiguez et al., 2012).

      Only some bacteria and archaea can synthesize cobalamin de novo. Among enteric bacteria, only two pathways have been identified for the initial corrin ring formation and the insertion of cobalt: an aerobic pathway in Pseudomonas denitrificans and an anaerobic pathway in Propionibacteria or Salmonella typhimurium. Since an industrial production process based on a 70-step chemical synthesis reaction is economically not feasible, the production of vitamin B12 is dependent on fermentation using species of Bacillus, Methanobacterium, Propionibacterium (i.e., P. freudenreichii and P. shermanii), Pseudomonas (i.e., P. denitrificans), and Rhodococcus (Jain et al., 2012; Wang et al., 2010;  2012). Industrial production is currently made by P. denitrificans using fermentation and metabolic engineering (Kang et al., 2012b; Li et al., 2012; Xia et al., 2015).

      Wang et al. (2016b) examined the connection between vitamin B12 biosynthesis by P. denitrificans and the morphological modifications. They observed that a reduced oxygen consumption rate (<2.0 mmol/g DCW/L) might stimulate the rapid production of this vitamin. This online monitoring approach could be successfully applied to enhance vitamin B12 fermentation on an industrial scale.

      Xia et al. (2015) developed a fermentation medium for the large-scale production of vitamin B12 using P. denitrificans. Corn steep liquor and maltose syrup performed well, obtaining a yield of 198.27 mg/L in a 120,000 L fermenter, a value close to that produced using refined sucrose (198.80 mg/L) and higher than that obtained using beet molasses (181.75 mg/L).

      2.2.2. Phenolic compounds

      Phenolic compounds are a vast class of secondary plant metabolites, which are responsible for defense against pathogen attack or stress. They inhere to a widespread and heterogeneous group of chemical components that possess one or more aromatic benzene rings with a conjugated aromatic system and one or more hydroxyl group (Bhattacharya et al., 2010; Cheynier, 2012). They present with diverse functions and structures, from relatively simple (i.e., phenolic acids) to polyphenols (i.e., flavonoids, lignans, ellagic acids, and stilbenes), which comprise at least two phenolic rings on their structure (Quideau et al., 2011). They are the most abundant dietary antioxidants with several thousand members identified in nature (Alu’datt et al., 2016; Cheynier, 2012; Lopes et al., 2016a; Marín et al., 2015). These compounds are usually secondary plant metabolites derived from the phenylpropanoid pathway. Flavonoids are the most diverse group of polyphenols that can be subcategorized into flavanones, flavones, isoflavones, flavonols, flavanols, and anthocynidins (Kumar and Pandey, 2013; Skrovankova et al., 2015; Zhang and Tsao, 2016). Natural polyphenols occur sparingly in free form, but are commonly conjugated together or with carbohydrates and organic acids. This makes it hard and unproductive to isolate and purify them via conventional extraction procedures (Chen et al., 2012; Nemitz et al., 2015). Reconstitution of tailored biosynthetic pathways in genetically superior microbial hosts (i.e., S. cerevisiae and E. coli) readily led to the heterologous production of several polyphenols, some of which have already established scale-up potential (Lin et al., 2014).

      Phenolic compounds have received attention because of their potent antioxidant properties in vitro, which have proven to be more powerful than ascorbic acid, vitamin E, and carotenoids (Dey et al., 2016; Queirós et al., 2016). With the rising interest in polyphenols and their metabolites, the microbial production of these compounds is increasing to prevent the restriction of human microbiota. Several methods have been developed to promote the bioconversion of these compounds using specific microorganisms or using enzymatic processes (Lopes et al., 2016a).

      Queirós et al. (2016) investigated the ability of three new biotechnological processes to enhance the bioactive properties of soymilk. One of the microbial processes was based on soymilk fermentation by probiotic lactic bacteria. The fermentation process also employed Lactobacillus delbrueckii ssp. bulgaricus (LB-340),

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