High Value Fermentation Products, Volume 1 E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Green technologies are no longer the "future" of science, but the present. With more and more mature industries, such as the process industries, making large strides seemingly every single day, and more consumers demanding products created from green technologies, it is essential for any business in any industry to be familiar with the latest processes and technologies. It is all part of a global effort to "go greener," and this is nowhere more apparent than in fermentation technology. This book describes relevant aspects of industrial-scale fermentation, an expanding area of activity, which already generates commercial values of over one third of a trillion US dollars annually, and which will most likely radically change the way we produce chemicals in the long-term future. From biofuels and bulk amino acids to monoclonal antibodies and stem cells, they all rely on mass suspension cultivation of cells in stirred bioreactors, which is the most widely used and versatile way to produce. Today, a wide array of cells can be cultivated in this way, and for most of them genetic engineering tools are also available. Examples of products, operating procedures, engineering and design aspects, economic drivers and cost, and regulatory issues are addressed. In addition, there will be a discussion of how we got to where we are today, and of the real world in industrial fermentation. This chapter is exclusively dedicated to large-scale production used in industrial settings.
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Contents
Cover
Title page
Copyright page
Foreword
About the Editors
List of Contributors
Preface
Acknowledgement
Chapter 1: Introduction, Scope and Significance of Fermentation Technology
1.1 Introduction
1.2 Background of Fermentation Technology
1.3 Market of Fermentation Products
1.4 Types of Fermentation
1.5 Classification of Fermentation
1.6 Design and Parts of Fermentors
1.7 Types of Fermentor
1.8 Industrial Applications of Fermentation Technology
1.9 Scope and Global Market of Fermentation Technology
1.10 Conclusions
References
Chapter 2: Extraction of Bioactive Molecules through Fermentation and Enzymatic Assisted Technologies
2.1 Introduction
2.2 Definition of Bioactives Compounds
2.3 Traditional Processes for Obtaining Bioactive Compounds
2.4 Fermentation and Enzymatic Technologies for Obtaining Bioactive Compounds
2.5 Use of Agroindustrial Waste in the Fermentation Process
2.6 General Parameters in the Optimization of Fermentation Processes
2.7 Final Comments
Acknowledgements
References
Chapter 3: Antibiotics Against Gram Positive Bacteria
3.1 Introduction
3.2 Target of Antibiotics Against Gram Positive Bacteria
3.3 Antibiotics Production Processes
3.4 Conclusion
References
Chapter 4: Antibiotic Against Gram-Negative Bacteria
4.1 Introduction
4.2 Gram-Negative Bacteria and Antibiotics
4.3 Production of Antibiotics
4.4 Conclusion
References
Chapter 5: Role of Antifungal Drugs in Combating Invasive Fungal Diseases
5.1 Introduction
5.2 Antifungal Agents
5.3 Targets of Antifungal Agents 5.3.1 Cell Wall Biosynthesis Inhibitors
5.4 Development of Resistance towards Antifungal Agents
5.5 Market and Drug Development
5.6 Conclusions
Acknowledgement
References
Chapter 6: Current Update on Rapamycin Production and its Potential Clinical Implications
6.1 Introduction
6.2 Biosynthesis of Rapamycin
6.3 Organic Synthesis of Rapamycin
6.4 Extraction and Quantification of Rapamycin
6.5 Physiological Factors Affecting Rapamycin Biosynthesis
6.6 Production of Rapamycin Analogs
6.7 Mechanism of Action of Rapamycin
6.8 Use of Rapamycin in Medicine
6.9 Side Effects of Long-Term Use of Rapamycin
6.10 Conclusions
Acknowledgements
References
Chapter 7: Advances in Production of Therapeutic Monoclonal Antibodies
7.1 Introduction
7.2 Discovery and Clinical Development
7.3 Structure and Classification
7.4 Nomenclature of Monoclonal Antibodies
7.5 Production of Monoclonal Antibodies
7.6 Conclusions
References
Chapter 8: Antimicrobial Peptides from Bacterial Origin: Potential Alternative to Conventional Antibiotics
8.1 Introduction
8.2 Classification of Bacteriocins
8.3 Mode of Action
8.4 Applications
8.5 Conclusions
Acknowledgments
Abbreviations
References
Chapter 9: Non-Ribosomal Peptide Synthetases: Nature’s Indispensable Drug Factories
9.1 Introduction
9.2 NRPS Machinery
9.3 Catalytic Domains of NRPSs
9.4 Types of NRPS
9.5 Working of NRPSs
9.6 Sources of NRPs
9.7 Production of Non-Ribosomal Peptides
9.8 Future Scope
Acknowledgements
References
Chapter 10: Enzymes as Therapeutic Agents in Human Disease Management
10.1 Introduction
10.2 Pancreatic Enzymes
10.3 Oncolytic Enzymes
10.4 Antidiabetic Enzymes
10.5 Liver Enzymes
10.6 Kidney Disorder
10.7 DNA- and RNA-Based Enzymes
10.8 Enzymes for the Treatment of Cardiovascular Disorders
10.9 Lysosomal Storage Disorders
10.10 Miscellaneous Enzymes
10.11 Conclusions
References
Chapter 11: Erythritol: A Sugar Substitute
11.1 Introduction
11.2 Chemical and Physical Properties of Erythritol
11.3 Estimation of Erythritol
11.4 Production Methods for Erythritol
11.5 Optimization of Erythritol Production
11.6 Toxicology of Erythritol
11.7 Applications of Erythritol
11.8 Precautions for Erythritol Usage
11.9 Global Market for Erythritol
11.10 Conclusions
References
Chapter 12: Sugar and Sugar Alcohols: Xylitol
12.1 Introduction
12.2 Biomass Conversion Process
12.3 Utilization of Xylose
12.4 Process Variables
References
Chapter 13: Trehalose: An Anonymity Turns Into Necessity
13.1 Introduction
13.2 Trehalose Metabolism Pathways
13.3 Physicochemical Properties and its Biological Significance
13.4 Trehalose Production
13.5 Application of Trehalose
13.6 Conclusions
References
Chapter 14: Production of Yeast Derived Microsomal Human CYP450 Enzymes (Sacchrosomes) in High Yields, and Activities Superior to Commercially Available Microsomal Enzymes
14.1 Introduction
14.2 Amounts of Microsomal CYP Enzyme Isolated from Yeast Strains Containing Chromosomally Integrated CYP Gene Expression Cassettes are far Higher than Strains Harbouring an Episomal Expression Plasmid Encoding a CYP Gene
14.3 Comparison of CYP Enzyme Activity of Yeast-Derived Microsomes (Sacchrosomes) with Commercially Available Microsomes Isolated from Insect and Bacterial Cells
14.4 IC
50
Values of Known CYP Inhibitors Using Sacchrosomes, Commercial Enzymes and HLMs
14.5 Stabilisation of Sacchrosomes through Freeze-drying
14.6 Conclusions
References
Chapter 15: Artemisinin: A Potent Antimalarial Drug
15.1 Introduction
15.2 Biosynthesis of Artemisinin in
Artemisia annua
and Pathways Involved
15.3 Yield Enhancement Strategies in
A. annua
15.4 Artemisinin Production Using Heterologous Hosts
15.5 Spread of Artemisinin Resistance
15.6 Challenges in Large-Scale Production
15.7 Future Prospects
References
Chapter 16: Microbial Production of Flavonoids: Engineering Strategies for Improved Production
16.1 Introduction
16.2 Flavonoids
16.3 Flavonoid Chemistry and Classes
16.4 Health Benefits of Flavonoids
16.5 Flavonoid Biosynthesis in Microorganism
16.6 Engineering of Flavonoid Biosynthesis Pathway
16.7 Metabolic Engineering Strategies
16.8 Applications of Synthetic Biology in Flavonoid Production
16.9 Post-modification of Flavonoids
16.10 Purification of Flavonoids
16.11 Conclusion
Acknowledgements
References
Chapter 17: Astaxanthin: Current Advances in Metabolic Engineering of the Carotenoid
17.1 Introduction
17.2 Pathway of Astaxanthin
17.3 Challenges/Current State of the Art in Fermentation/Commercial Production
17.4 Metabolic Engineering for Astaxanthin
17.5 Future Prospects
References
Chapter 18: Exploitation of Fungal Endophytes as Bio-Factories for Production of Functional Metabolites through Metabolic Engineering; Emphasizing on Taxol Production
18.1 Introduction
18.2 Taxol: History and Clinical Impact
18.3 Endophytes
18.4 The Plausibility of Horizontal Gene Transfer (HGT) Hypothesis
18.5 Endophytes as Biological Factories of Functional Metabolites
18.6 Taxol Producing Endophytic Fungi
18.7 Molecular Basis of Taxol Production by
Taxus
Plants (Taxol Biosynthetic Pathway)
18.8 Metabolic Engineering for Synthesis of Taxol: Next Generation Tool
18.9 Future Perspectives
Acknowledgements
References
Index
End User License Agreement
Guide
Cover
Copyright
Table of Contents
Begin Reading
List of Tables
Chapter 2
Table 2.1
Enzymatic biotransformation of polyphenols....
Table 2.2
Potential waste obtained from industrial activity and agriculture in Mexico....
Table 2.3
General aspects evaluated in the optimization fermentation process....
Chapter 3
Table 3.1
Different classes of β-Lactams antibiotics, according to their chemical...
Table 3.2
Classification of Penicillins....
Table 3.3
Different generation of Cephalosporins....
Chapter 4
Table 4.1
List of gram-negative bacteria and infections caused by them....
Table 4.2
Five generations of cephalosporins....
Table 4.3
Classification of Penicillin....
Table 4.4
List of mutagens used in strain improvement....
Table 4.5
Negative impact of glucose as a carbon source on the yield of various antibiotics....
Table 4.6
Separation techniques used in antibiotic purification from fermentation broth [154]....
Chapter 5
Table 5.1
Most prevalent fungal diseases in humans....
Table 5.2
Global estimates and related deaths due to fungal infections per year in AIDS...
Table 5.3
Global incidences of some fungal diseases [3]....
Table 5.4
Status and activity of current and approved oral and intravenous antifungals....
Table 5.5
Antifungal agents used in fungal therapy....
Table 5.6
Natural producers of Echinocandins [93]....
Table 5.7
Naturally produced fungal cell wall inhibitors [89]....
Table 5.8
Natural Sordarin producing strains [157]....
Table 5.9
Targets identified for novel antifungal drugs under development....
Table 5.10
Summary of mode and mechanism of Antifungal drugs....
Chapter 6
Table 6.1
Optimization of different methods for rapamycin production....
Table 6.2
Optimization of different fermentation methods for rapamycin production....
Table 6.3
List of Rapamycin analogs /derivatives and their activities....
Chapter 7
Table 7.1
List of Therapeutic Monoclonal Antibodies along with their source of origin and...
Table 7.2
Nomenclature scheme of mAbs [26, 27]....
Table 7.3
List of MAbs-producing cell lines along with their respective products....
Chapter 8
Table 8.1
Therapeutic potential of bacteriocins....
Chapter 9
Table 9.1
Non-ribosomal peptides based drugs reported in literature....
Table 9.2 (a)
Examples of bacterial/actinobacterial metabolites along with their uses and producing...
Chapter 10
Table 10.1
List of FDA approved therapeutic enzymes....
Chapter 11
Table 11.1
Types of sugar substitutes [2]....
Table 11.2
Comparison of sugar alcohols and sugar....
Table 11.3
Types of sugar alcohols and their applications....
Table 11.4
Amount of erythritol in various foods [8]....
Table 11.5
Chemical and physical properties of different sugar alcohols [8]....
Table 11.6
List of various erythritol producing microorganisms [36]....
Chapter 12
Table 12.1
Composition of various lignocellulosic materials [12]....
Table 12.2
Physical properties of xylitol [18, 19]....
Table 12.3
Xylitol presence in fruits and vegetables [19]....
Table 12.4
Effect of various detoxification methods on xylitol productivity and yield obtained...
Table 12.5
Xylitol producing yeast strains....
Table 12.6
Influence of initial substrate concentration on the fermentation parameters for...
Table 12.7
Influence of aeration on xylitol production in yeasts with D-xylose as substrate....
Chapter 13
Table 13.1
Prevalent pathways for trehalose synthesis in living systems....
Chapter 14
Table 14.1
The non-fluorescent substrates that were used and the fluorescent products formed...
Table 14.2
Comparison of IC50 values of known CYP enzyme inhibitors using Sacchrosomes, commercial...
Chapter 15
Table 15.1
Yield of artemisinin and its precursors in heterologous plant production platforms....
Chapter 16
Table 16.1
Different classes of flavonoids with examples....
Table 16.2
Flavonoid compounds produced in microbial hosts....
Chapter 17
Table 17.1
Significant values of astaxanthin yield from studies reviewed....
Chapter 18
Table 18.1
Various biotechnological approaches for the production of taxol other than obtaining...
Table 18.2
A list of taxol-producing endophytic fungi isolated from yew associated and...
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
High Value Fermentation Products Volume 1
Human Health
Edited by
Saurabh Saran
Vikash Babu
Asha Chuabey
This edition first published 2019 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA
© 2019 Scrivener Publishing LLC
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-119-46001-5
Foreword
From last two decades we have witnesses unprecedented growth and development in biotechnology positioning the bioeconomy as a major indicator of advancement. Today, the global fermentation-based industry is already worth over 127 billion dollars. Based on the experience and expertise in this filed, we are trying to collect the different technologies advancement and products developed in biotechnology. This book ‘High Value Fermentation Products-Volume 1 (Human Health) is divided into various important sections related to Human Health like antibiotics, sugar & sugar alcohols, enzymes, nutraceuticals, metabolic engineered derived products, this will help the readers to understand the importance of fermentation derived product for the betterment of human health. This book will also help to overcome of various bottle necks of the Industry/scientific community and shall be useful for the betterment of the society and environment. This book will also shares an insight into the recent research, cutting edge technologies, high value products, industrial demand which bring immense interest among young and brilliant researchers, cultivated scientists, industry personnals and talented student communities. The contents of the book have been designed in such a way that it is providing extensive coverage of new developments, state of the art technologies, current and future trends in biotechnology and fermentation. The reader will be introduced with basic and advanced methodologies on industrial microbiology and fermentation technology. The main goal of this book is to share and enhance the knowledge of each and every individual in the fermentation world.
Ram A VishwakarmaDirector, CSIR-IIIM
About the Editors
Dr. Saurabh Saran, PhD, is a Fermentation Scientist having experience in Industrial microbiology, Biotechnology and Fermentation Technology for more than 15 years. Dr. Saran has completed his PhD from Delhi University, India. Dr. Saran has got hands-on experience in working both industries and academic. He has worked in the industries like Reliance Industries Ltd., India. Later he was appointed as a Research Professor at Republic of Korea, South Korea. He has also worked as a Coordinator at the Technology Based Incubator, Delhi University South Campus, Delhi, Inida. Presently, he is working as a Senior Scientist, Fermentation technology division, CSIR-IIIM, Jammu, India. He has an expertise on the screening, isolation, production and scale up of Industrial Enzymes, Biochemicals & Biofuels. Expert in process development/engineering, scale up to 5L, 10L, 30L, 100, 300 L & 500L fermentation size, (batch, fed batch and continuation fermentation) strain engineering, downstream processing and applications of industrially important biomolecules. To my credentials, I have 3 patents and more than 25 international publications in peer reviewed international journals on fermentation technology.
Dr. Vikash Babu, PhD was born in Bulandshahr district of Uttar Pradesh, India on 1st September 1981. He did his Bachelor’s degree from I.P (PG) College Bulandshahr, India. After qualifying all India combined entrance exam for biotechnology conducted by JNU, New Delhi, India, he did his degree in Biotechnology from Kumaun University, Nainital. After completing his M.Sc degree, he qualified many national level competitive exams such as DBT-JRF- 2005, CSIR-UGC NET for lecturership- Dec. 2004 & June 2005 and GATE-2005. In Nov. 2005, he joined as a DBT-JRF in the Department of Biotechnology, Indian Institute of Technology, Roorkee under the superivision of Dr. Bijan Choudhury and registered for the Ph.D in the same department and Institute and completed his Ph.D degree in the year 2011. After finishing his Ph.D research work he joined Mangalayatan University, Beswan, Aligarh (India) as a lecturer. He left Manglayatan University in the year 2012 and joined Graphic Era University, Dehradun (India) as an assistant professor where he worked till June 2013. Currently, he is working as a scientist in CSIR-IIIM.
Dr. Asha Chaubey, Ph.D is Principal Scientist and Head of Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India. She has about 15 years of research experience in the area of enzymology and fermentation technology. She is actively engaged in development of indigenous process development. Her research interests include exploration and exploitation of microorganisms for production of enzymes and bioactives in special reference to industrial applications. She has published research articles in the area of bioactives production, enzyme immobilization, biotransformation, kinetic resolution of racemic drug intermediates. She has also published several review articles and has been actively involved in the development of biosensors for health care and environmental monitoring and has several patents on lactate and cholesterol biosensors.
List of Contributors
Akankszha Dwivedi,Biochemical Engineering Research and Process Development Centre CSIR- Institute of Microbial Technology, Chandigarh, (India)
Alok Malaviya,Department of Life Sciences, CHRIST (Deemed To Be University), Hosur Road, Bengaluru, (India)
Anil Agarwal,Department of Chemistry, CHRIST (Deemed To Be University), Hosur Road, Bengaluru, (India)
Anshela Koul,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu
Apurwa Kestwal,National Institute of Biologicals (Ministry of Health & Family Welfare) Government of India Plot No.A-32, Sector-62 Institutional Area, NOIDA, (U.P.), (India)
Aravind Madhavan,Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, (India)
Asha Chaubey,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, (India)
Ashok Pandey,CSIR- Indian Institute for Toxicology Research (CSIR-IITR), 31 MG Marg, Lucknow, (India)
Babbal, Adivitiya,Department of Microbiology, University of Delhi South Campus, New Delhi, (India)
Bhabatosh Chaudhuri,CYP Design Ltd, The Innovation Centre, 49 Oxford Street, Leicester, LE1 5XY, (UK)
Bhumica Agarwal,Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut, (India)
Cristóbal N. AguilarGroup of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Debendra K. Sahoo,Biochemical Engineering Research and Process Development Centre CSIR- Institute of Microbial Technology, Chandigarh, (India)
Dignya Desai,Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, (India)
Divya Gupta,Department of Life sciences, Uttarakhand Technical University, Dehradun, (India)
Edgard GnansounouEcole Polytechnique Federale de Lausanne, ENAC GR-GN, GC A3, Station 18, CH-1015, Lausanne, (Switzerland)
Girijesh K. Patel,Department of Oncologic Sciences, University of South Alabama, Mobile, (USA)
Gurdeep Singh,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Harikrishna Reddy,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Himanshu Verma,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Hitesh Sharma,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu(India)
Ibidapo Stephen Williams,CYP Design Ltd, The Innovation Centre, 49 Oxford Street, Leicester, LE1 5XY, (UK)
Ivanoe García,Group of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Jayesh Varavadekar,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Jitender Nandal,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Kakoli Dutt,Department of Bioscience and Biotechnology, Banasthali Vidyapith, Rajasthan (India)
Kanti N. Mihooliya,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Karan Malhotra,National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bengaluru, (India)
Katherine Saikia,Department of Life Sciences, CHRIST (Deemed To Be University), Hosur Road, Bengaluru, (India)
KB Arun,Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, (India)
Lalit Kumar Singh,Department of Biochemical Engineering, School of Chemical Technology, Harcourt Butler Technical University Kanpur, (India)
Leonardo Sepulveda,Group of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Liliana Londoño-Hernández,Group of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Lipsy Chopra,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
M. Sudhakara Reddy,Department of Biotechnology, Thapar University, Patiala 147004 (India)
Mahendra Pal Singh,National Institute of Biologicals (Ministry of Health & Family Welfare) Government of India Plot No.A-32, Sector-62 Institutional Area, NOIDA, (U.P.), (India)
Manali Datta,Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, (India)
Manmeet Ahuja,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Mansi Vora,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Maryam Faiyaz1,Department of Bioengineering, Integral University, Lucknow, Dasauli, (India)
Parameswaran Binod,Microbial Processes and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala (India)
Piyush Sethia,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Pradeep Kumar,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Puja Tandon,School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, PR (China)
Rahul Vikram Singh,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu(India)
Ramita Taggar,Biochemical Engineering Research and Process Development Centre CSIR-Institute of Microbial Technology, Chandigarh, (India)
Ramón Larios-Cruz,Group of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Raúl Rodríguez-HerreraGroup of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Raveendran Sindhu,Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, (India)
Ravi S. Manhas,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, (India)
Ricardo Gómez-García,Group of Bioprocesses. Food Research Department, School of Chemistry, Universidad Autónoma de Coahuila, Saltillo, Coahuila, (México)
Richa Sharma,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, (India)
Richi V Mahajan,National Institute of Biologicals (Ministry of Health & Family Welfare) Government of India Plot No.A-32, Sector-62 Institutional Area, NOIDA, (U.P.), (India)
Ruchika Goyal,Department of Biotechnology, Graphic Era University, Dehradun, (India)
Sanjog Garyali,Key Laboratory of Synthetic Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, (China).
Saurabh Saran,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, (India)
Shikha Gupta,Gujarat State Biotechnology Mission, Gandhinagar, (India)
Shilpa Mohanty,Department of Microbiology, University of Delhi South Campus, New Delhi, (India)
Subhash Chand,National Institute of Biologicals (Ministry of Health & Family Welfare) Government of India Plot No.A-32, Sector-62 Institutional Area, NOIDA, (U.P.), (India)
Surinder Singh,National Institute of Biologicals (Ministry of Health & Family Welfare) Government of India Plot No.A-32, Sector-62 Institutional Area, NOIDA, (U.P.), (India)
Syed M. Waheed,Department of Biotechnology, Graphic Era University, Dehradun, (India)
Vidhya Rangaswamy,High Value Chemicals, Breakthrough R & D, Reliance Industries Limited. Reliance Corporate Park. Thane Belapur Road, GhansoliNavi Mumbai, (India)
Vikash Babu,Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu
Yogender Pal Khasa,Department of Microbiology, University of Delhi South Campus, New Delhi, (India)
Yong Wang,Key Laboratory of Synthetic Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, (China).
Preface
A century after the pioneering work of Louis Pasteur, the science of microbiology has reached to its zenith. In a short span of time, modern biotechnology has grown up drastically from a laboratory scale to a commercial level. Advances in Fermentation Technology have created a favorable niche for the development of fermentation based products to facilitate their applications and to provide a sustainable environment for mankind and to improve the quality of human life. The modern day biotechnology offers many opportunities and effective techniques to address the human concerns in the areas of pharmaceuticals, diagnostics, polymers, textiles, aquaculture, forestry, chemicals, household products, environmental cleanup, food processing, feed and forensics etc.
The book entitled “High Value Fermentation Products” has been divided in different volumes namely, Human Health and Human Welfare. The Volume 1 of the book has 18 chapters focussed on basics to fermentation technology, antibiotics & immunosuppressants, antibodies, peptides & proteins, sugars & sugar alcohols and metabolic engineering derived products. The fist chapter entitled ‘Introduction, scope and significance of fermentation technology’ aims to provide the insights on the basics of fermentation technology to the readers. The second chapter on ‘Extraction of bioactive molecules through fermentation and enzymatic assisted technologies’ elaborates the techniques involved in isolation of bioactive molecules and other chemo-enzymatic approaches for bioactives production. Third and fourth chapters compile the important antibiotics against Gram positive and Gram negative bacteria discovered so far. Fifth chapter emphasizes on the role of antifungal drugs in combating invasive fungal diseases. Sixth chapter provides the update on rapamycin production and its potential clinical implications. The seventh chapter on ‘Advances in production of therapeutics monoclonal antibodies’ highlights the methodologies involved in the production of monoclonal antibodies for therapeutics. The eighth and ninth chapters focus on the antimicrobial peptides of microbial origin and their mechanism of production. The chapter tenth provides the insight on the therapeutic enzymes for human disease management. Chapters eleven to thirteen focus on the strategies involved in the production of natural sweeteners erythritol, xylitol and trehalose. Chapter fourteen describes how production of yeast derived microsomal human CYP450 enzymes (Sacchrosomes) with high yields and activities are superior to other commercially available microsomal enzymes. Chapters fifteen and sixteen compile the methodologies for production of artemisinin and flavonoids respectively. The chapter seventeen provides the information on how advances in metabolic engineering of the carotenoids can be useful for production of astaxanthin. The last chapter of the volume 1 describes how fungal endophytes can be exploited as bio-factories for production of functional metabolites through metabolic engineering, with special reference to taxol production.
This book provides deep insights on the strategies decisive factors involved in the fermentation based high value products like antibiotics, enzymes and other therapeutic secondary metabolites in the area of human health. We are confident that this book will be useful to students, researchers, academicians, and industry professionals interested in studying fermentation technology.
Editors
Acknowledgement
The Editors take this opportunity to gratefully acknowledge the assistance and contribution of the people who have faith in us in this undertaking for compiling of the Book “‘High Value Fermentation Products”-Volume 1 (Human Health).
We are in debt of Dr. Ram A. Vishwakarma, Director, CSIR-Indian Institute of Integrative Medicine, Jammu for his valuable and esteemed guidance to carry out this task. His scholarship and authorative knowledge has been a great source of motivation and inspiration.
First and foremost, it is not enough to express our gratitude in words to all the contributors for devotion and providing excellent matter of chapters on time.
The help and support provided by Mr. Chand Ji Raina, Mr. R.K. Khajuria and Mrs. Urmila Jamwal, was important and we acknowledge all of them with sincere thanks.
We are also thankful to the students of Fermentation Technology Division, CSIR-IIIM for their sincere efforts, dedication and determination to achieve objectives for the completion of this task in a given time.
Where emotions are involved, words cease to mean for our family members for the consistent motivation during the planning and edition of this book.
We avail the opportunity to express our heartiest thanks to ‘Almighty’ for pouring His care and blessings throughout and making this work a success.
Saurabh SaranVikash BabuAsha Chaubey
Chapter 1Introduction, Scope and Significance of Fermentation Technology
Saurabh Saran1*, Alok Malaviya2 and Asha Chaubey1
1Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, (India)
2Department of Life Sciences, CHRIST (Deemed To Be University), Hosur Road, Bengaluru, (India)
*Corresponding author: [email protected]
Abstract
Fermentation technology is a field which involves the use of microorganisms and enzymes for production of compounds that have applications in the energy, material, pharmaceutical, chemical and food industries. Though fermentation processes have been used for generations as a requirement for sustainable production of materials and energy, today it has become more demanding for continuous creations and advancement of novel fermentation processes. Efforts are directed both towards the advancement of cell factories and enzymes, as well as the designing of new processes, concepts, and technologies. The global market of microbial fermentation technology was valued at approximately USD 1,573.15 million in 2017 and which is expected to generate revenue of around USD 2,244.20 million by end of 2023. However, regular supply of materials, such as nutrients, microorganisms, the complex nature of production process, and high manufacturing cost hinder the market growth.
Keywords: Fermentation, world market, fermenter design, submerged fermentation, solid state fermentation
1.1 Introduction
In the present century, we are witnessing a revolution in biotechnology that has far-reaching implications in different industries like pharmaceuticals, food and feed, polymer, oleo-chemicals, textiles, leather, cosmetics and agriculture, consequently resulting in the betterment of the society beyond anything previously imaginable in the history of science. The present scenario defines biotechnology as “any technique that uses living organisms or substances to make or modify a product, to improve plants and animals, or to develop microorganisms for specific and beneficial uses” [1]. Thus, biotechnology encompasses tools and techniques, including those of recombinant DNA technology for improving the living organisms, which may be plant, animal or microorganism. The product formed can be new or rare, that is, not having existed before naturally, or being less abundant than for certain needs or purposes. Thus, biotechnology is a multidisciplinary pursuit involving a variety of natural sciences such as cell and molecular biology, microbiology, physiology, biochemistry and genetics.
In terms of microbiology, biotechnology refers to the use of microorganisms such as bacteria, yeast and fungi or other biological substances produced from them, to perform important industrial processes. Although, era of advanced technology is not very new, the roots of fermentation technology are known for over 6,000 years, when beer was first fermented. Today, biotechnology has intersected and redefined our lives by producing a large variety of value-added products and biomolecules such as antibiotics, enzymes, hormones, organic acids and other metabolites [2].
Broadly, fermentation is a process used to produce a specific product by living organisms. Examples of fermentation processes include the production of simpler products such as baker’s yeast and alcohols, as well as complex products such as therapeutic proteins, antibiotics, enzymes, and genetically engineered materials. Fermentation processes should be carefully and critically monitored with regards to the culture conditions and time of harvest depending on the desired product. Typically, fermentation is a natural process. People applied fermentation to make products such as cheese, wine, meat, and beer long before the biochemical process was understood.
1.2 Background of Fermentation Technology
In the 1850s and 1860s, Louis Pasteur became the first scientist to study fermentation, when he demonstrated that fermentation was caused by living cells, i.e., yeast. His work was influenced by the earlier work of Theodor Schwann, the German scientist who helped to develop the cell theory. Around 1840, Schwann had concluded that fermentation is the result of processes that occur in living things. In 1857, Pasteur showed that lactic acid fermentation is caused by living organisms. In 1860, he also demonstrated that souring in milk is caused by bacteria. This process was earlier thought to be a chemical change. Pasteur’s work to identify the role of microorganisms in food spoilage, thus led to the process of pasteurization. While working to improve the French brewing industry, Pasteur published his famous paper on fermentation, Etudes sur la Biere in 1877, which was translated into English in 1879 as Studies on Fermentation. He defined fermentation (incorrectly) as “Life without air,” but correctly showed specific types of microorganisms cause specific types of fermentations and specific end products.
Eduard Buchner, a German chemist received the Nobel prize in 1907 for showing that enzymes in yeast cells cause fermentation. About two decades later, two other scientists namely Arthur Harden and Hans Euler-Chelpin won the Nobel prize in 1929 for their work who showed how enzymes cause fermentation. Further by 1940s, fermentation based antibiotics production technology was established.
A British scientist, Chain Weizmann (1914-1918) developed a fermentor for the first time for the production of acetone during First World War. But, the first large scale fermentor (above 20 litre capacity) was used for the production of yeast in 1944 (3). Later, importance of aseptic conditions for fermentation process was recognised, which led to the designing and construction of piping, joints and valves in which sterile conditions could be achieved. The large scale aerobic fermentors consisting of a large cylindrical tank with air introduced at the base via network of perforated pipes were used for the first time, in central Europe in 1930’s for the production of compressed yeast. Later, modifications were made to design of mechanical impellers to increase the rate of mixing and to break up and disperse the air bubbles. Baffles on the walls of the vessels were useful to prevent formation of vortex in the liquid. A system in which the aeration tubes were introduced with water and steam for cleaning and sterilization was patented by Strauch and Schmidt in 1934.
After the decision of British Govt. in 1934 on inadequate surface fermentation processes, use of submerged culture technique was realized for penicillin production. Essential aseptic conditions, with good aeration and agitation were probably the most important factors, which led to the development of carefully designed and purpose-built fermentation vessels. Hindustan Antibiotic Ltd., Pimpri, Pune established the first pilot fermentor in India at in the year 1950.
1.3 Market of Fermentation Products
Market Definition
Fermentation medium used in the fermentation process to help increase the pace of the process play a vital role as process initiators in an array of applications. Catalysts or process-enhancing chemicals also contribute in the manufacturing cost, chemical reaction time (fermentation time) as well as energy consumption and making the fermentation process more economically attractive. Natural occurring, low cost and productivity enhancing features of fermentation chemicals find applications in a multiple of industries worldwide.
Market Segmentation
The global fermentation chemicals market is divided on the basis of type of product developed
Organic Acids
Alcohols (Ethanol and Other Alcohols)
Enzymes
Others (Antibiotics, Vitamins, Xanthan, etc.)
The global fermentation chemicals market is divided on the basis of Industrial application developed,
Alcohol Industry
Plastics & Fiber Industry
Pharmaceutical & Nutritional Industry
Food & Beverages Industry
Other Industries
1.4 Types of Fermentation
Fermentation is one of the oldest scientific domains which has evolved, refined and been diversified over the centuries. Fermentation processes are mainly classified as either (A) solid state or (B) submerged culture. Solid state fermentation (SSF) differs from submerged fermentation (SmF) with respect to flowing water, which is present in SmF while it is absent or very minor in SSF. In the following sections, we have discussed various aspects of solid-state and submerged fermentation processes.
1.4.1 Solid State Fermentation (SSF)
The growth of microorganisms on moist solid substrate particles in the absence or minimum water between the particles is known as solid state fermentation. The moisture content of solid substrate ranges between 12–80%. SSFs are usually used for the fermentation of agricultural products or foods. Some food fermentations involving SSF: Wheat by Aspergillus, Soybean by Rhizopus, Soybean by Aspergillus. During SSF, the substrate may require preparation or pretreatment, like chopping or grinding-reduce particle size, cooking or chemical hydrolysis pasteurization or sterilization-reduce contaminants. Usually a filamentous fungus requiring aerobic condition is used and the inoculum is mixed into substrate for fermentation.
The origin of Solid-state fermentation (SSF) can be traced back to bread-making process in ancient Egypt. SSF processes are those microbiological processes in which growth and product formation takes place on and inside the humidified solid substrate [4]. In this case, processes occur in the absence or near absence of free water. There are four interacting phases present in such processes which include (i) a gas phase, (ii) a solid insoluble support, (iii) a liquid phase containing dissolved substrates and products, and (iv) a biotic phase formed by the microorganisms. Fundamentally, six different types of solid-state fermenters (SSFr) are commonly used, which include – (i) Tray, (ii) Rotary drum, (iii) Packed-bed, (iv) Swing solid state, (v) Stirred vessel, (vi) Air solid fluidized bed bioreactor. Further, based on mixing and aeration, Mitchell [5] divided SSFr into the following four groups:
Group-I – the bed is static or mixed occasionally; air is circulated around the bed.
Group-II – bed is static or mixed occasionally; air is passed forcefully through the bed.
Group-III – bed is continuously mixed; air is circulated around the bed.
Group IV – bed is agitated; air is passed forcefully through the bed.
Based on the type of solid substrate used, SSF systems have been divided into: (i) those employing natural material as solid substrate, (ii) those employing inert support impregnated with liquid medium [6]. Different agro-industrial wastes such as cassava bagasse, sugarcane bagasse, sugarbeat pulp/husk, orange bagasse, oil cakes, wheat bran, coir pith, coffee pulp/husk, okaraetc are used as natural solid substrates, selection of which depends on some physical parameters such as particle size, moisture level, intra-particle spacing and nutrient composition within the substrate [6].
Factors affecting SSF performance: SSF needs close process parameters monitoring and control, which is very difficult practically. There are various factors which affect the performance of SSF processes, some of which include –
Biological Factors –
These influence the behavior of the microbial species used in SSF.
Selection of a suitable strain
is one of the most important criteria in SSF. Next comes the
selection of substrate
to be used, which depends on the factors related to cost and availability. Then comes the
inoculum size,
and the size of inoculum determines the biomass production. Too low or too high concentration of inoculum is often undesirable and does not give the expected outcome.
Moisture and water activity –
As compared to submerged fermentation, the low moisture content becomes limiting for growth and metabolism of microbes in solid-state. Water activity (A
W
) is a useful parameter which is frequently used during SSF to characterize the energetic state of water [7]. Quantitative studies of water relations in SSF have suggested that microbial activity is strongly influenced by water activity of substrates and it determines the type of organism that can grow on given substrate during SSF and, the microbial metabolic production and excretion could be modified by controlling this parameter [7–8].
Temperature and heat transfer –
Temperature and heat transfer processes in substrate bed has also been reported to greatly influence the microbial growth and metabolite production during SSF processes. A large amount of heat is generated due to metabolic activities of microbes and since the substrates used during SSF have low thermal conductivities, heat removal is decreased resulting in accumulation of heat within the system. Therefore, heat removal to maintain the optimal temperature for growth and metabolite production by microbes becomes the key issue during SSF processes. Additionally, moisture also needs to be controlled, thus coupled control of moisture and temperature becomes an important issue for consideration during SSF [6].
Off-Gas analysis –
Measuring microbial biomass and growth kinetics during SSF is another major challenge and hence it might affect the repeatability and reproducibility of results. However, this could be addressed by establishing a correlation with CO
2
production, which correlates well with microbial metabolism and even low physiological activity could be indicated by this method.
Mass transfer –
SSF rate and efficiency is strongly affected by mass transfer limitations [9–11]. Mass transfer in SSF involves:
Micro-scale phenomenon – this depends on inter and intra particle O
2
and CO
2
diffusion, enzyme, nutrient absorption and metabolite formation.
Macro scale phenomenon – this depends on airflow (inflow and outflow), substrate type, design of bioreactor, substrate mixing, inter-particle space, variation in particle size and microbes used. Therefore, for maximum mass transfer process the optimally designed SSF bioreactors should be selected.
Applications of SSF:
Previously, SSF process was famous for “low volume - high cost” products due to critical technical problems associated with heat and mass transfer for large capacity. But with advancement in SSF technology, this process is inclining towards “high volume - high cost” products. SSF has been successfully applied in various industrial processes where submerged fermentation proves to be challenging. Some of the industrial processes where SSF has successfully been applied include:
Enzyme production – this is one of the most important applications of SSF. Some of the advantages of SSF over submerged fermentation for enzyme production include high yield and volumetric productivities along with low cost of and lesser waste generation [6]. Some of the reported enzymes produced through SSF are protease, lipase, cellulose, pectinase, phytase, L-glutaminase, amylase, ligninase, xylanase, etc.
Organic acid production – Some of the organic acids produced via SSF includes lactic acid and gallic acid [12–17].
Secondary metabolite production – There are various secondary metabolites which have been produced using SSF. Some of those products include gibberellic acids [18–20], aroma production [21–23], antibiotics [24–28].
Poly-gamma glutamate production [29]
Poly unsaturated fatty acid production [30]
Biocontrol agent production [31–32]
Advantages of solid state fermentation:
SSF has several advantages which makes it an attractive technology to be used for production of the above-mentioned industrially important products. Some of these advantages include [33]:
Higher product titer
Low capital and recurring expenditure
Low waste water production
Reduced energy requirements
Absence of foaming problem
Simple and highly reproducible
Simpler fermentation media
Less space requirement
Easier aeration
Economic to use even at smaller scale
Lower cost of downstream processing
However, there are several limitations of SSF, some of which are listed below:
Exposure of fungal hyphae to an air phase, which might desiccate them
Rise of temperature well above the optimum level due to inadequate removal of waste metabolic heat resulting in temperature variation during growth in SSF
Poor availability of nutrients to the organisms due to large concentration gradients of nutrients within the particles
Poor oxygen availability to a significant proportion of the biomass
Need to use indirect methods for biomass measurement
pH control during SSF is almost impossible
Difficult to control the moisture content of the medium
Microbial types that could be used in SSF are limited
Limited knowledge on engineering and development aspects
To a large extent, the above-mentioned limitations of SSF could be addressed by another mode of fermentation popularly known as submerged fermentation. In the next section, we will briefly discuss various aspects of submerged fermentation.
1.4.2 Submerged Fermentation (SmF)
Submerged fermentation is the cultivation of microorganisms in liquid nutrient broth. Industrial enzymes/other products can be produced using this process. This involves growing carefully selected microorganisms (bacteria and fungi) in closed vessels containing a rich broth of nutrients (the fermentation medium) and a high concentration of oxygen. Production medium is required for growth of microorganism as well as production of primary and secondary metabolites. Submerged fermentations have been mainly used to produce flowable formulations.
Contrary to SSF, submerged fermentation (SmF) are those microbiological processes in which growth and product formation take place using substrate present in liquid form. There are three main modes of SmF – (i) Batch mode, (ii) Fed-Batch mode, (iii) Continuous mode. Most industrial fermentation processes, except a few, operate as simple batch or fed-batch process. In order to develop an industrially applicable production process for a desired product, one must understand these three modes of fermenter operation.
Batch mode – Batch culture is the simplest mode of operation. Here, initially all the nutrients required for the organism’s growth and product formation are added in one vessel at the start of the fermentation process. This is followed by medium sterilization and inoculation of the vessel with desired organism for growth and product formation. This mode of operation operates as closed system and in between nothing is added into the vessel, except air. Finally, fermentation is terminated when either all the nutrient is exhausted or the desired concentration of product is achieved.
Advantages of batch mode of operation –
Simple to use
Operability and reliability
Remote chances of contamination during process
Can be handled by relatively inexperienced operator
Fed-batch mode – This is similar to batch process, except that these do not operate as closed systems. In this mode, one or more substrates, nutrients, and/or inducers are added in between during the process. This mode is normally used to extend the productive phase of the process.
Advantages of fed-batch mode of operation –
‘Catabolite repression’ and ‘Crabtree effects’ could be controlled by controlling limiting substrate concentration
Organism’s growth rate and subsequent oxygen demand could be controlled
High cell density of the cells could be achieved
Increased production of non-growth related metabolites could be achieved
This mode of operation could help in reducing the broth viscosity, when needed
Continuous mode – In this mode of operation, the organisms are fed with fresh nutrients while removing the spent medium and cells at same rate so as to ensure that factors like culture volume, biomass, product and substrate concentrations along with pH, temperature and dissolved oxygen are constant during the process.
Advantages of continuous mode of operation -
Feed flow rate could be optimized to improve the productivity and growth rate
Longer period of productivity and shorter down time
High cell density of cells could be achieved by cell recycling
Best system to study culture physiology
All the three modes of operation have their advantages and could be opted depending on the final objective and problems being tried to be solved.
Major factors influencing submerged fermentation output: There are several biological as well as physical parameters which can affect the output of submerged fermentation output, and some of them include:
Microbial strain
Inoculum stage, age, size
Medium components
pH
Temperature
Agitation and aeration
Dissolved oxygen concentration
Broth viscosity
Foaming
1.4.3 Solid State (SSF) vs. Submerged (SmF) Fermentation
A comparison between SSF and SmF has been presented in following table:
1.5 Classification of Fermentation
Most of the industrial fermentation processes use batch or fed-batch procedures, although continuous fermentation can be more economical, if sterility conditions are properly maintained.
Batch fermentation: In a batch process, all the ingredients are combined and the reactions proceed without any further input. Batch fermentation has been used for millennia to make bread and alcoholic beverages, and it is still a common method, especially when the process is not well understood. However, it can be expensive because the fermentor must be sterilized using high-pressure steam between batches. Strictly speaking, there is often addition of small quantities of chemicals to control the pH or suppress foaming.
Table 1.1 Comparison between solid state and submerged fermentation.
Parameter
SSF
Submerged fermentation
Nature of substrate
Solid
Liquid
Volumetric productivity
Relatively low
High
Energy requirements
Relatively high
Low
Aeration control
Relatively difficult to meet the requirement
Relatively easier to meet the requirement
Downstream processing
Relatively difficult
Relatively easier
Risk of desiccation of microbe used
High
No
Inoculum used
Inoculum sprayed on surface medium
Inoculum is usually in liquid form
Temperature control
Difficult to achieve
Not overly difficult
pH control
Difficult to provide
Relatively easier to provide
Availability of nutrients to the microbes
Cannot be controlled within narrow limits if needed by the process
Can be controlled within narrow limits if needed, through feeding
Availability of oxygen to the biomass
Cannot be controlled at a particular level of saturation
Can be controlled reasonably at a particular level of saturation of the medium
Contamination problem
Relatively high
Low
Power consumption
Relatively low
High
Labour required
Relatively high
Low
Foaming
No
Yes
Batch fermentation goes through a series of phases. There is a lag phase in which cells acclimatise to the new environment once the cell adopt to the new environment then exponential growth occurs which is also known as log phase. The growth slows down and becomes non-exponential when many of the nutrients have been consumed, but production of secondary metabolites accelerates. This continues through a stationary phase after most of the nutrients have been consumed, and then the cells die.
Fed-batch fermentation: Fed-batch fermentation is a variation of batch fermentation where some of the ingredients are added during the fermentation. Through fed batch process production of the desired product can be controlled as per need during the fermentation process. Addition of a limited quantity of nutrients during the non-exponential growth phase increases the production of secondary metabolites.
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