Biotechnology

(Multi-Volume Set)

Executive Editor of the Series: J.N. Govil

Vol. 1: Animal Biotechnology

Guest Editors: BHASKAR GANGULY & SOHINI DEY

Vol. 2: Plant Biotechnology

Guest Editor: P. ANANDA KUMAR

Vol. 3: Microbial Biotechnology

Guest Editor: PROF. RUPINDER TEWARI

Vol. 4: Applied Synthetic Biology

Guest Editor: VIJAI SINGH

Vol. 5: Gene and Protein Engineering

Guest Editor: JITENDRA K. THAKUR

Vol. 6: Bioinformatics and Computational Biology

Guest Editor: A.R. RAO

Vol. 7: Drug Discovery

Guest Editor: K.K. BHUTANI

Vol. 8: Novel Drug Delivery

Guest Editors: BHUPINDER SINGH & O.P. KATARE

Vol. 9: Diseases and Theranostics

Guest Editor: SURENDER S INGH

Vol. 10: Nanobiotechnology

Guest Editor: ASHOK KUMAR

Vol. 11: Biodegradation and Bioremediation

Guest Editor: PROF. MASOOD AHMAD

Vol. 12: Bioprocess Engineering

Guest Editor: SHISHIR SINHA
BIOTECHNOLOGY
Volume 12

Bioprocess Engineering

Guest Editor
Shishir Sinha
Professor of Chemical Engineering
Indian Institute of Technology, Roorkee
Roorkee – 247 667, India

•
Executive Editor
J.N. Govil
Former Principal Scientist, Division of Genetics
Indian Agricultural Research Institute
New Delhi – 110 012, India

2014

Studium Press LLC, U.S.A.

Guest Editor: Shishir Sinha
Executive Editor: J.N. Govil

BIOTECHNOLOGY
Volume 12

Bioprocess Engineering
© 2014 Publishers

This book contains information obtained from authentic and highly

regarded sources. Reprinted material from authentic sources which
are acknowledged and indicated. A wide variety of references are listed.
Reasonable efforts have been made to publish reliable data and
information, but the editors and the publisher cannot assume
responsibility for the validity of all materials or for the consequences
of their use.
All rights are reserved under International and Pan-American
Copyright Conventions. Apart from any fair dealing for the purpose of
private study, research, criticism or review, as permitted under the
Copyright Act, 1956, no part of this publication may be reproduced,
stored in a retrieval system or transmitted, in any form or by any
means–electronic, ele ctrical, chemical, mechanical, optical,
photocopying, recording or otherwise–without the prior permission of
the copyright owner.

ISBN : 1-62699-027-1
SERIES ISBN : 1-62699-015-8

Published by:
STUDIUM PRESS LLC
P.O. Box 722200, Houston, TX 77072 - U.S.A.
Tel: (281) 776-8950, Fax: (281) 776-8951
E-mail: studiumpress@gmail.com
Website: http://www.studiumpress.in

Printed at:
......................................
 Biotechnology Series
(12 Vols. Set)
FOREWORD

It is a daunting task to write a foreword for this extraordinary effort of

editing 12 Volumes, having more than 500 authors, from all over the
globe, spanning into 189 Chapters, covering some 5000 pages. It is
heartening to see this truly massive effort resulting in reading material
which is scientifically exciting and at the same time indicating practical
uses. I should like to compliment the executive editor, guest editors
and authors for these endeavours.
I am delighted to see the very first volume on Animal Biotechnology
of such great importance to India which has over 350 million cattle.
Many efforts to carry out breakthrough technologies have not been
successful. Of course, vaccines have helped and so also artificial
insemination. Since the dosages of drugs are large, for instance in camels
and elephants, it is all the more important to look more deeply into this
subject.
In the recent past biopharmaceuticals have made a big dent and
more successes appear to be round the corner. The extraordinary success
of erythropoietin may be pointed out, apart from insulin. The supposedly
ordinary example of ‘vegetarian’ renin was no mean achievement. In
agrochemicals also we are witnessing some breakthroughs. A number
of products deserve to have a bio-route to avoid animal origin, e.g.
heparin, L-crysteine, etc.
Some biotechnology products are doing very well compared to
synthetic processes e.g. citric acid, L-lysine, COQ 10, etc. By contrast
some products like fumaric acid, 1,4 butanadiol, etc. face severe
competition from petrochemical routes. Even in the case of 1,3
propanediol, in spite of massive improvements in the bioroute,
competition from the petrochemical route exists.
Downstream processing in biotechnology takes closer to 80% of the
capital investment but also it receives only 20% attention. Even in the
case of interferon downstream processing was crucial. A number of
advances have taken place and these are duly covered in the
compendium.
vi Biotechnology Vol. 12: Bioprocess Engineering

Enzyme Engineering witnesses many improvement including

immobilized versions and biphasic systems.
Plant breeding practices have seen spectacular successes like in the
case of hybrid wheat/rice/corn, etc. a remarkable achievement was
breeding rape, C-22 lipid, to cannola, C-18 lipid, which transformed the
global edible oil industry. With increasing global population,
concomminant decrease land availability and water stress, the plant
biotechnology will play a critical role.
A recent study had indicated as to why many biotechnology companies
faced hurdles and this was associated with a weak linkage with academia.
There has been a lot of discussion globally on genetically modified
crops. We may like to rewind ourselves that when mechanical
implements were first developed in the U.K. there was a hue and cry
about their employment and even said that it will ruin agriculture!
Most vaccines have utilized genetic engineering which the public is using
extensively.
Biotechnology is at a center stage whether for conversion of
agroresidues to biofuels or for therapeutic purposes and these volumes
are most welcome and I have great pleasure in supporting these
endeavours and recommend acquiring them in Libraries

Date: 22nd October, 2013 Professor M. M. Sharma

2/3 Jaswant Baug (Runwal Park),
Behind Akbarallys, Chembur Naka,
Mumbai - 400 071, India
[Brief Profile of Prof. M.M. Sharma: Professor Man Mohan Sharma (popularly called
Professor M. M. Sharma) is the most regarded engineering personality from India.
Prof. Sharma (b. 1937) obtained B. Chem. Eng. (1958), M.Sc. (Tech.) (1960) from
University Department of Chemical Technology (UDCT), now renamed as Institute of
Chemical Technology (ICT), Mumbai and Ph.D. (Chemical Engineering) (1964) from
Cambridge University. After returning to India, he served as Professor of Chemical
Engineering at ICT (1964-1997) and also became Director of the Institute (1989-1997).
Prof. Sharma has made extensive contributions to chemical engineering science and
technology. He has published over 250 research papers in highly reputed international
Chemical Engineering Journals. He has supervised 71 Doctoral Thesis and 35 M. Chem.
Eng. / M. Sc. (Tech.) Thesis and has been an active consultant to Industry since 1964.
In 1990, he became the first engineering scientist from India to be honoured with
Fellowship of Royal Society (FRS) United Kingdom, which is considered as one of the
highest honours after the Nobel Prize. He was awarded the Padma Bhushan (1987)
and the Padma Vibhushan (2001) by the Government of India. Professor Sharma is a
recipient of a number of prestigious academic honours and awards including the S. S.
Bhatnagar Prize in Engineering Sciences (1973), FICCI Award (1981), the Vishwakarma
medal of the Indian National Science Academy (1985), G.M. Modi Award (1991),
Meghnad Saha Medal (1994), Leverhulme Medal of the Royal Society (1996) and Medal
for Promotion and Service to Science (2008)].
 vii

About the Editors

Dr. Shishir Sinha

Dr. Shishir Sinha is working as Professor  in

Department of Chemical Engineering, Indian Institute
of Technology, Roorkee, India. Doctorate from Indian
Institute of Technology, Kanpur, India, Dr. Sinha is
having more than thirteen years of teaching and research
experience. His area of expertise is polymer surface
modification. He has published more than 90 papers in
international, national journals and conferences. He has
handled several research projects and guided various M.Tech and Ph.D.
students in the area of chemical engineering. Dr. Sinha has published
two books in the area of Polymers.

Dr. J.N. Govil

Dr. J.N. Govil (b. 1945): Obtained his Masters and
Doctorate degrees from Agra University, Agra, India.
In his career span of 41 years research experience at
the Indian Agricultural Research Institute, New Delhi,
Dr. Govil has been involved in the breeding of cross-
pollinated, often cross-pollinated, and self-pollinated
crops. His research is mainly focussed on breeding for
better quality, disease resistance, and for higher
productivity in Pennisetum, Sorghum, maize, chickpea, and pigeonpea.
Dr. Govil has been well exposed to the international scientific community
through various training programmes. He took his training in “Plant
exploration and collection techniques” through IBPGR in 1982. He was
also awarded the prestigious FAO/IBPGR Fellowship in “Genetic
resources, evaluation, and data preparation and management” at the
University of Birmingham, UK. In 1983, he made visits to gene banks
located in Europe. He also participated in various international seminars
viii Biotechnology Vol. 12: Bioprocess Engineering

and conferences, including “Food and Legume Improvement for Asian

Farming Systems” in Thailand in 1986. Dr. Govil is credited with more
than ninety research papers in various journals of national and
international repute in various aspects of genetics, crop breeding, and
topics on general agriculture. He has written and edited a number of
books on medicinal Plants (2 Vols each of two Titles) and other books
with international authors. A new series “Recent Progress in Medicinal
Plants” has been published by Studium Press, LLC, USA in 40 volumes
under Dr. Govil’s Chief Editorship. Dr. Govil has been Editor-in-Chief
of the Journals, New Botanist (An International Journal of Plant
Research) and Glimpses in Plant Research, since 1988. He has also
guided more than a dozen post-graduate students. Dr. J.N. Govil was
actively engaged through his leadership on pigeonpea breeding with
special emphasis on “Breeding short duration pigeonpea varieties for
improved management and low input conditions.” Through his intensive
efforts over the last 20 years, nine varieties of early pigeonpea in arhar-
wheat rotation have been released at national level. Dr. Govil retired
from ICAR service during the year 2007. Presently, he is working as
Publishing Director and Managing Editor with Studium Press LLC,
USA and has brought out nearly 300 academic publications during last
six years. E-mail: jngovil@gmail.com; jngovil@hotmail.com
 ix

List of Contributors

Alves José Guilherme Lembi Ferreira: Departament of Food Science,

University Federal of Lavras – UFLA, Lavras, Brazil.
Azbar Nuri: 1Ege University, Bioengineering Department, 35100, Bornova-
Izmir/Turkey; 2Ege University, Center for Environmental Studies,
35100, Bornova-Izmir/Turkey.
Baadhe Rama Raju: Department of Biotechnology, National Institute of
Technology Warangal – 506004, A.P, India.
Barzegari Abolfazl: Research Center for Pharmaceutical Nanotechnology,
Tabriz University of Medical Sciences, Tabriz, Iran.
Begum Sarkar: Department of Chemical Engineering, Ryerson University,
Toronto, M5B 2K3 Ontario, Canada.
Bhavanam Anjireddy: Department of Chemical Engineering, National
Institute of Technology Warangal – 506004, A.P, India.
Bhowal Saibal: Department of Food Engineering, Central Food
Technological Research Institute, Council of Scientific and Industrial
Research, Mysore – 570020, India.
Chanukya B.S.: 1Department of Food Engineering, Central Food
Techn ological Research In stitute, Council of Scientific and
Industrial Research, Mysore – 570 020; 2Academy of Scientific and
Innovative Research, Central Food Technological Research Institute,
Mysore – 570 020, India.
Covas Dimas Tadeu: 1Hemotherapy Center of Ribeirão Preto, Faculty of
Medicine of Ribeirão Preto, University of São Paulo. Tenente Catão
Roxo street, 2501, CEP 14051-140, Ribeirão Preto-SP, Brazil;
2
Department of Medical Clinic, Faculty of Medicine of Ribeirão Preto,
Café av w/n. CEP 14040-903, Ribeirão Preto-SP, Brazil.
Dahman Yaser: Department of Chemical Engineering, Ryerson
University, Toronto, M5B 2K3 Ontario, Canada.
Eckard Anahita D.: Department of Agricultural and Biosystems
Engineering, South Dakota State University, 1400 North Campus
Drive, Brookings, SD 57007, USA.
Elias Élen Cristina L.: Laboratory of Bioprocess Engineering, Food
Engineering Department, School of Food Engineering, University of
x Biotechnology Vol. 12: Bioprocess Engineering

Campinas (UNICAMP), R. Monteiro Lobato, 80, Campinas-SP, 13083-

862, Brazil.
Evtuguin Dmitry V.: Centre for Research in Ceramics and Composite
Materials (CICECO), Department of Chemistry, University of Aveiro,
Campus Universitário de Santiago, 3810-193, Portugal.
Filho Francisco Maugeri: Laboratory of Bioprocess Engineering, Food
Engineering Department, School of Food Engineering, University of
Campinas (UNICAMP), R. Monteiro Lobato, 80, Campinas-SP, 13083-
862, Brazil.
Forte Marcus Bruno Soares: Laboratory of Bioprocess Engineering, Food
Engineering Department, School of Food Engineering, University of
Campinas (UNICAMP), R. Monteiro Lobato, 80, Campinas-SP, 13083-
862, Brazil.
Gibbons W.R.: South Dakota State University, Brookings, SD 57007, USA.
Gibbons William: Department of Biology and Microbiology, South Dakota
State University, 1400 North Campus Drive, Brookings, SD 57007, USA.
Guimarães Isabela Costa: Departament of Food Science, University
Federal of Lavras – UFLA, Lavras, Brazil.
Gungormusler Mine: Ege University, Bioengineering Department
– 35100, Bornova-Izmir/Turkey.
Hongzhang Chen: Institute of Process Engineering, Chinese Academy of
Sciences, China.
Jamrógiewicz Marzena: Medical University of Gdansk, Faculty of
Pharmacy with Subfaculty of Laboratory Medicine, Hallera 107, 80-
416 Gdansk, Poland.
Karunanithy C.: Food and Nutrition Department, University of Wisconsin-
Stout, Menomonie WI 54751, USA.
Khani Sajjad: Research Center for Pharmaceutical Nanotechnology,
Tabriz University of Medical Sciences, Tabriz, Iran.
Kim Bo-Kyung: Department of Biotechnology, College of Natural
Resources and Life Science, Dong-A University, Busan – 604714, Korea.
Lan Wang: Institute of Process Engineering, Chinese Academy of Sciences,
China.
Lee Bo-Hwa: Department of Biotechnology, College of Natural Resources
and Life Science, Dong-A University, Busan – 604714, Korea.
Lee Eun-Jung: Department of Biotechnology, College of Natural Resources
and Life Science, Dong-A University, Busan – 604714, Korea.
Lee Jin-Woo: Department of Biotechnology, College of Natural Resources
and Life Science, Dong-A University, Busan – 604714, Korea.
Mazutti Marcio A.: Chemical Engineering Department, Federal
University of Santa Maria, Av. Roraima, 1000, Santa Maria-RS, 97105-
900, Brazil.
Menezes Evandro Galvão Tavares: Departament of Food Science,
University Federal of Lavras – UFLA, Lavras, Brazil.
List of Contributors xi

Mizukami Amanda: Hemotherapy Center of Ribeirão Preto, Faculty of

Medicine of Ribeirão Preto, University of São Paulo. Tenente Catão
Roxo Street 2501, CEP 14051-140, Ribeirão Preto-SP, Brazil.
Mohtasebi Banafsheh: Department of Chemical Engineering, Ryerson
University, Toronto, M5B 2K3 Ontario, Canada.
Mozaffari Farhad Ein: Department of Chemical Engineering, Ryerson
University, Toronto, M5B 2K3 Ontario, Canada.
Muthukumarappan Kasiviswanathan: Department of Agricultural and
Biosystems Engineering, South Dakota State University, 1400 North
Campus Drive, Brookings, SD 57007, USA.
Namasivayam S. Karthick Raja: Department of Biotechnology,
Sathyabama University, Chennai 119, Tamil Nadu, India.
Nandini K.E.: Biotechnology Department, Jaypee Institute of Information
Technology, A-10, Sector-62, Noida – 201307, Uttar Pradesh, India.
Omidi Yadollah: 1 Research Center for Pharmaceutical Nanotechnology,
Tabriz University of Medical Sciences, Tabriz, Iran; 2Perelman School
of Medicine, University of Pennsylvania, Philadelphia, USA
Peng Cheng: Key Laboratory of Molecular Biophysics, The Ministry of
Education, College of Life Science and Technology, Huazhong
University of Science and Technology, Wuhan 430074, P.R. China.
Peng Mao: Jiangnan University, China.
Prabakaran G.: Department of Biotechnology, Sathyabama University,
Chennai 119, Tamil Nadu, India.
Priyanka B.S.: Department of Food Engineering, Central Food
Technological Research Institute, Council of Scientific and Industrial
Research, Mysore – 570020, India.
Putatunda Chayanika: Lovely Professional University, Punjab, India.
Rastogi Navin K.: 1Department of Food Engineering, Central Food
Technological Research Institute, Council of Scientific and Industrial
Research, Mysore – 570 020; 2Academy of Scientific and Innovative
Research, Central Food Technological Research Institute, Mysore –
570 020, India.
Rehman-Ur Hamood Mian: Department of Chemical Engineering,
Ryerson University, Toronto, M5B 2K3 Ontario, Canada.
Rodrigues Maria Isabel: Laboratory of Bioprocess Engineering, Food
Engineering Department, School of Food Engineering, University of
Campinas (UNICAMP), R. Monteiro Lobato, 80, Campinas-SP, 13083-
862, Brazil.
Salic Anita: University of Zagreb, Faculty of Chemical Engineering and
Technology, Marulicevtrg 19, HR-10000, Zagreb, Croatia.
Sastry R.C.: Department of Chemical Engineering, National Institute of
Technology Warangal – 506004, A.P, India.
Singh Shalini: School of Biochemical Engineering, Indian Institute of
Technology (BHU), Varanasi – 221005, India.
xii Biotechnology Vol. 12: Bioprocess Engineering

Singh Utkarsh: School of Biochemical Engineering, Indian Institute of

Technology (BHU), Varanasi – 221005, India.
Sinha Rupika: School of Biochemical Engineering, Indian Institute of
Technology (BHU), Varanasi – 221005, India.
Srivastava Pradeep: School of Biochemical Engineering, Indian Institute
of Technology (BHU), Varanasi – 221005, India.
Suazo Claudio Alberto Torres: Department of Chemical Engineering,
Federal University of São Carlos, Washington Luís Road, Km 235, CEP,
13565-905, São Carlos, Brazil.
Swiech Kamilla: 1Department of Pharmaceutical Sciences, Faculty of
Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo.
Café av w/n. CEP 14040-903, Ribeirão Preto-SP, Brazil; 2Hemotherapy
Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto,
University of São Paulo. Tenente Catão Roxo Street, 2501, CEP 14051-
140, Ribeirão Preto-SP, Brazil.
Tavares Ana P.M.: LSRE-Laboratory of Separation and Reaction
Engineering, Associate Laboratory LSRE/LCM. Department of
Chemical Engineering, Faculty of Engineering, University of Porto. Rua
Dr. Roberto Frias s/n. 4200-465 Porto, Portugal.
Thierie Jacques: Université Libre de Bruxelles Faculty of Sciences
Department, Interfaculty School of Bioengineers (EIB), Belgium.
Tišma Marina: Faculty of Food Technology Osijek, J.J. Strossmayer
University of Osijek, F. Kuhaèa 18, HR-31000, Osijek, Croatia.
Tusek Ana Jurinjak: University of Zagreb, Faculty of Food Technology
and Biotechnology, Pierottijeva 6, HR-10000, Zagreb, Croatia.
Velic Natalija: Faculty of Food Technology Osijek, J.J. Strossmayer
University of Osijek, F. Kuhaèa 18, HR-31000, Osijek, Croatia.
Wasewar Kailas L.: Advance Separation and Analytical Laboratory,
Department of Chemical Engineering, Visvesvaraya National Institute
of Technology (VNIT), Nagpur – 440010, India.
Xavier Ana M.R.B.: Centre for Research in Ceramics and Composite
Materials (CICECO), Department of Chemistry, University of Aveiro,
Campus Universitário de Santiago – 3810193, Portugal.
Yan Yun-Jun: Key Laboratory of Molecular Biophysics, The Ministry of
Education, College of Life Science and Technology, Huazhong
University of Science and Technology, Wuhan 430074, P.R. China.
Yingyi Duan: Institute of Process Engineering, Chinese Academy of
Sciences, China.
Zelic Bruno: Faculty of Chemical Engineering and Technology, University
of Zagreb, Marulicev trg 19, HR-10000 Zagreb, Croatia.
 xiii

SERIES ISBN : 1-62699-015-8

About the Series

Hungarian agriculture scientist Karl Ereky in 1919 coined the term

Biotechnology describing the merging of biology and technology. The
simplest definition of biotechnology can, therefore, be given as a
technology based on biology. A more precise definition of biotechnology
is the controlled and deliberate manipulation of biological systems
(whether living cells or cell components) for the efficient manufacture or
processing of useful products.

The biological processes of microorganisms have been used for

thousands of years in agriculture, food production and medicine. Over
7,000 years ago, the Egyptians were making wine, beer, vinegar and
bread using fermentation techniques based on an understanding of the
microbiological processes that occur in the absence of oxygen. There
were more than 50 varieties of bread in Egypt more than 4,000 years
ago. Yogurt was produced by lactic acid bacteria in milk and molds
were used to produce cheese.

Plants were long recognized as genetic resources of economic growth.

Queen Hatshepsut of Egypt in 1495 BC sent a team of plant collectors
to the Land of Punt (present day Somalia and Ethiopia) to gather
specimens of exotic plants. Christopher Columbus and other explorers
introduced corn of America to the rest of the world. Spanish navigators
brought potatoes from Andes in South America to European countries.
A single coffee tree from Arabia planted in the Amsterdam Botanical
Garden in 1706 originated most of the coffee grown today in South
America. Likewise, the British started growing Chinese tea plants in
the foothills of the Himalayas to establish an economic base in the
colonies. By the late 19th century, India had displaced China as the
main exporter of tea to Britain.

Dutch experimentalist Anton van Leeuwenhoek, commonly known

as the father of microbiology, in 1676 examined scrapings from his teeth
under a microscope and discovered microbes. Two centuries later in
1864, the French chemist Louis Pasteur developed the pasteurization
xiv Biotechnology Vol. 12: Bioprocess Engineering

process to destroy harmful microorganisms in products using heat. This

process allowed products to be transported over long distances without
spoiling. Alexander Fleming discovered the antibiotic substance
penicillin from the mould Penicillium notatum in 1928. Penicillin is the
most efficacious life-saving drug in the world and has altered forever
the treatment of bacterial infections.

The science of ‘genetics’ was born in 1906. The genetics tried to explain
how organisms both resemble their parents and differ from them. By
the 1920s genetics was helping plant breeders improve their crops. The
science of genetics was transformed by the discovery of deoxyribonucleic
acid (DNA). DNA molecule carries the hereditary information in the
cells. Although, the chemical DNA was first isolated by Swiss physician
Friedrich Miescher in 1869, but was not taken seriously as the chemical
basis of genes until 1953 when James Watson and Francis Crick for the
first time cleared the mysteries around the DNA as a genetic material.
Watson and Crick suggested that the DNA structure is a double helix -
two strands twisted around each other like a spiral staircase with bars
across like rungs. The structure, function and composition of DNA are
virtually identical in all living organisms. Only the precise sequence of
the chemical base in the DNA molecule makes each creature unique.

The discovery of HIV/AIDS in 1980s as a deadly disease has helped

biotechnologists tremendously to improve their tools employed for
applications in various aspects of day-to-day life. Ian Wilmut and Keith
Campbell in 1996 successfully cloned a female domestic sheep named
‘Dolly’, which was the first mammal to be cloned using the process of
nuclear transfer. Craig Venter, in 2000, was able to sequence the human
genome. In 2010, Craig Venter has been successful in demonstrating
that a synthetic genome could replicate autonomously. All these
discoveries have unlimited implications and applications.

Because of the intense research activities and the rapid increase of

knowledge in the field of biotechnology, it appeared desirable to set up
a landmark under the name “Recent Developments in Biotechnology”.
It is a twelve volume collection of referred review and research articles
written by some of the leading researchers active in the field. Through
this collection, the editors have endeavoured to illustrate the breadth
and depth of a subject that is inspiring, motivating and challenging our
scientists since 17th century and is shaping the current century in a big
manner. These twelve volumes cover almost all aspects of biotechnology
world including animal biotechnology, plant biotechnology, microbial
biotechnology, systems and synthetic biotechnology, gene and protein
engineering, computational biology, medical and nano biotechnology,
bioremediation and bioprocess/biochemical engineering.
About the Series xv

Volume 1: Animal Biotechnology

Volume 2: Plant Biotechnology
Volume 3: Microbial Biotechnology
Volume 4: Applied Synthetic Biology
Volume 5: Gene and Protein Engineering
Volume 6: Bioinformatics and Computational Biology
Volume 7: Drug Discovery
Volume 8: Novel Drug Delivery
Volume 9: Diseases and Theranostics
Volume 10: Nanobiotechnology
Volume 11: Biodegradation and Bioremediation
Volume 12: Bioprocess Engineering
Volume 1 features the diversified nature of field of animal
biotechnology and brings forth the significant advancements of the field.
The volume aptly covers the key areas of the field including livestock
biotechnology, aqua-biotechnology and insect biotechnology. The volume
goes beyond the conventional animal health and productivity
biotechnologies and delves into many topics covering the creation and
application of biotechnology-derived animal models for human health.

Volume 2 bestows upon the three core areas of plant biotechnology,

namely plant genetic engineering, molecular breeding and genomics.
The volume presents articles on molecular markers, pest management,
gene regulation and improvement, oxidative stress in plants, tools to
isolate plant proteins, antioxidants, antifreeze proteins, transgenic
plants, plant-associated endophytic bacteria and biological control of
plant pathogens.

Volume 3 exhibits the influence of modern techniques on different

branches of microbiology such as agriculture, environment, industrial
and medic al. This v olume includes ar ticles on microbial
polygalacturonases, exopolysaccharides, lipases, xylanases, proteolytic
enzymes, biofilms, peptide antibiotics, bio-fertilizers, microalgal biofuels,
food grade microbial pigments and biochemical routes for biogas
production.

Volume 4 brings together biologists and engineers for designing and

construction of novel biological systems, gene networks and biosynthetic
pathways through better understanding of principles of biological
mechanisms. This volume contains articles on systems and synthetic
biology, complex networks in systems biology, structural DNA
nanotechnology, synthetic molecules in biosensors, targeted genome
xvi Biotechnology Vol. 12: Bioprocess Engineering

engineering, biological computing, biotechnology and bioethics,

microfluidic systems in synthetic biology and analysis of dynamical
systems.

Volume 5 demonstrates the progress made in the field of life sciences

in past few decades through ground breaking researches made in gene
and protein engineering. The volume deals with the chapters on next
generation sequencing, small regulatory RNA, microRNA, xylanases,
gene expression profiling, craniosynostosis and genetic engineering,
enzyme design, L-Tyrosinase, loop-mediated isothermal amplification,
and nutrigenetics and nutrigenomics.

Volume 6 takes into account the extensive research efforts made in

the fields of bioinformatics and computational biology that have led to
the development of tools, softwares, computational techniques, statistical
approaches, simulation techniques and mathematical models to study
the biological systems. The chapters in this volume address issues
related to Next Generation Sequencing data analysis, allele mining,
modeling of protein structure and G-protein coupled receptors,
microarrays in genomics research, livestock genomics, gene regulatory
network, systems biology, genetic diversity analysis of animals and
protein ligand interactions.

Volume 7 on drug discovery and development primarily concentrates

on discovery of lead molecules, updates on antimicrobials and current
status of biotherapeutics development. This volume comprises discussion
on novel lead molecules from plant sources, natural genistein, microbes
based cancer therapy, natural and synthetic antimicrobial peptides,
biosynthesis of Beta-lactam antibiotics, stem cell research in human
and veterinary therapeutics, depression and its treatment, urea
transporter inhibitors, non-steroidal anti-inflammatory drugs, novel
polyene antifungal formulations and best practices in biopharmaceutical
drug development.

Volume 8 is a compilation of diverse novel approaches to strategically

deliver the drugs to the desired site at the desired rate and concentration.
This volume focuses on cyclodextrin nanoformulations as drug carriers,
colon drug delivery, colloidal drug delivery, pulmonary drug delivery,
targeted drug delivery, Janus particles and carbon nanotubes in drug
delivery applications, ionic liquids as pharmaceutical carriers, cell
permeable peptides, herbosomes, implantable drug delivery systems,
chitosan-based drug delivery systems and recent developments in drug
delivery systems and in mouth dissolving tablets formulations and
designs.
About the Series xvii

Volume 9 on diseases and theranostics summarizes our current

understanding of the molecular mechanisms that govern cell death in
normal and malignant cells and examines the treatment opportunities
for selective killing of these cells. This volume incorporates chapters on
diagnosis and treatment of sepsis, amniotic membranes, biomarkers of
diabetes, tumor microenvironment targeting and molecular imaging in
cancer research, vector borne diseases, hepatitis B virus, fungal
infections, bacterial, protozoan and viral life-threatening diseases and
anti-phospholipid syndrome in pregnancy complications

Volume 10 is devoted to applications of nano biotechnology to relevant

fields like agriculture, environmental biotechnology and nanomedicines
for treatment of chronic and acute diseases. The volume emphasizes on
biopolymeric nanocarriers, tissue engineering, myconanoparticles,
selenium nanoparticles, metal nanoparticles, transition metal carbide
nanoparticles, microbial nanotechnology, nano biosensors, stabilization
of single enzymes, animal disease diagnosis, waste water treatment and
bio-conjugated nanoparticles for cancer imaging and therapy.

Volume 11 presents the overview and recent trends in the field of

biodegradation and bioremediation. The cost- effective and eco-friendly
bioremediation techniques aim at remove space the environmental
contaminants with the help of biological organisms and/or their
components. This volume explores the topics as diverse as bacterial
and fungal degradation of dioxins, petroleum hydrocarbons, pesticides,
polycylic aromatic hydrocarbons and industrial effluents, applications
of enzymes and biosurfactants in bioremediation, overview of the work
on metal remediation via biosorption process, recent technological
approaches of bioremediation and biodegradation of vegetable waste
for cellulase production.

Volume 12 highlights the applications of bioprocess/biochemical

engineering in the production of green fuels and several other value
added products from wastes or biological materials. This volume provides
a discussion on many environment friendly fuels such as biogas,
synthesis gas, ethanol, biodiesel and biobutanol, role of bioreactors in
tissue engineering, reactive extraction for the recovery of carboxylic
acids, biopharming and bioprocessing of plantibodies, application of
biotechnology in pulp and paper industry and production of cellulase
and xylanase enzymes from agro-wastes.

The chapters in these vol umes are contributed by senior

academicians/researchers, each writing about his or her particular area
of expertise. The main requirement for these chapters has been that
they should give a reasonably complete up-to-date account of the current
xviii Biotechnology Vol. 12: Bioprocess Engineering

state of affairs in these areas and they should be understandable to

students and non-professionals who, in every possibility, may not belong
to same level of knowledge and experience. The level of these chapters
is consistent with the degree of complexity inherent in each chapter,
but is adaptable to non-professionals. All chapters contain a list of
references by means of which more details and more materials on the
chapter can be found by interested readers.

The statistics of the series are quite interesting: 12 volumes

containing 238 chapters covering around 6364 pages contributed by more
than 625 authors spread over 39 countries across the globe. This has
only been made possible through the commitments of its contributors
who have generously shared the results of their studies; the guidance
and support of the editorial team and advisers, the dedicated efforts of
art staffs at Studium Press; and the cooperation and assistance of many
other individuals.

The series Recent Developments in Biotechnology is believed to be

of interest to students, engineers, medical professionals, scientists and
technologists involved in academic institutions, research laboratories
and/or industry. Biotechnology industry greatly depends on close ties
with leading academic institutions than any other high-technology
industry. Although the ideas that arise in the academic environment
are different in forms from those in which they are realized commercially.
This series will form a pathway between industry scientists and
academics to convey the most promising ideas.

The series editors put on record their gratitude to all contributing

authors who enthusiastically accepted their requests and made great
efforts to write chapters for a wide audience. The length of these chapters
varies considerably depending on the topic. Some of them have the
appearance of a small book. Their authors deserve special thanks for
their painstaking efforts and generosity in choosing to publish their
work in this series. The editors also thank the referees for their hard
work to ensure the high quality of the chapters. Last but definitely not
the least, the editors put on record their gratitude to uncredited
contributor without whom the work of this magnitude was never
possible.
Guest Editors &
Executive Editor of the Series
 xix

Preface

Bioprocess/Biochemical Engineering is a combination of several

disciplines of science, engineering and technology, such as agriculture,
biology, biotechnology, chemical engineering and mathematics.
However, the scope of bioprocess and biochemical engineering is not
restricted to these disciplines only and may include the work of
electrical, mechanical and industrial engineers as well to utilize
fundamentals of these additional disciplines. It deals with the design
and development of equipments (bioreactors, fermentors, etc.) and
processes (mode of operations, yield optimization, quality of end
product, etc.) for the manufacturing of products such as food, feed,
biopharmaceuticals, biochemicals, biopolymers, nutraceuticals and
paper from biological materials and water treatment industries
through processes based on living cells or sub component of such cells
to serve the needs of society.
This final volume of multi-volume series on Recent Developments
in Biotechnology is an effort to cover the diverse aspects of bioprocess
and biochemical engineering and their applications in different areas
spanning tissue engineering, green liquid and gaseous fuels and
production of enzymes and other value-added products from agro-
wastes. The highlights of the chapters of this volume are recited as
under to express the essence of the knowledge cherished in them.
Biogas is a clean and renewable form of energy derived from a
variety of sources, such as cattle dung, poultry wastes, plant wastes
(husk, grass, weeds, etc.), domestic wastes (vegetable peels, waste
food material), human excreta, industrial wastes (wastes from food
processing industries, starch industries, sugar industries, fisheries,
etc.), energy crops like tropical sugar beet, sweet sorghum, municipal
solid waste and slaughterhouse waste. The chapter 1 presents an
introductory article on the principles of formation of biogas which is
now-a-days considered as an approachable solution of growing energy
needs of the human race across the globe.
xx Biotechnology Vol. 12: Bioprocess Engineering

Biomass is the name given to the plant matter, which is created

by photosynthesis process where water and carbon dioxide in
presence of solar energy is converted into organic matter.
Syn(thesis)gas is a fuel gas mixture consisting primarily of hydrogen,
carbon monoxide and some carbon dioxide. The chapter 2 discusses
the characteristics of various biomasses and the production of syngas
from them. The process principles and the technological aspects of
various gasification systems are also discussed in the article. The
chapter 3 reviews the different pretreatment methods usually applied
to biomass materials for biochemical conversion, namely acid, alkali,
hydrothermal, wet oxidation, extrusion, microwave irradiation,
ozone, organosolv, cellulose solvent, microbial and combinations in
depth.

Liquid biofuels are eco-friendly, locally available and reliable fuels

obtained from biomass. Alcohols (methanol, ethanol and butanol) and
biodiesel are liquid fuels which can be used in a similar way to
conventional oil fuels to run internal combustion engines in vehicles
or generators. The chapter 4 describes the role of amphiphiles in
economical production of ethanol from biomass by reducing
fermentation time and the amount of enzyme used for saccharification
of biomass. The chapter 5 provides a discussion on cost-effective
enzymatic catalysis techniques for industrial scale production of
biodiesel or other high-value products from biomass with good
commercial efficiency. The chapter 6 offers an extensive discussion
on biological production of butanol, which is considered as a next
generation fuel superior to bioethanol. The chapter 7 reports the
results of experimental study carried out for the production of ethanol
from the pressed coffee pulp. A yield of 25.63 g ethanol/L of medium
was obtained at the end of fermentation. However, the need to pre-
treat raw materials to obtain higher levels of ethanol was noted in
the study.

The chapter 8 comprises a discussion on the state-of-art of the

application of white-rot fungi in solid-state fermentation processes
used for the production of lignolytic enzymes (laccase, lignin-
peroxidase and manganese-peroxidase), bioethanol, biogas and other
value-added products. The chapter 9 studies the interaction between
physical properties of cultivation substrate and microorganism growth
in solid state fermentation. The authors also report methods invented
by them to quantify the microbial biomass in solid state fermentation
by image process and fractal dimension.
Preface xxi

Microreactors are miniaturized reaction systems fabricated by

using methods of microtechnology and precision engineering. These
reactors offer several fundamental advantages over conventional
macroreactors, such as large surface-to-volume ratio, excellent mass
and heat transfer, short residence times, smaller amount of reagents,
catalyst and waste products, laminar flow, effective mixing, better
process control and small energy consumption. The chapter 10 gives
an overview of the recent developments in the field of application of
microtechnology in biotechnology with special emphasis on the
application of microreactors in biotransformations. Bioreactors play
an important role in tissue engineering, as they provide technical
means to perform controlled studies with reproducible production of
tissue constructs in specific environments. The chapter 11 summarizes
the important aspects of bioreactor design and provides an overview
of existing concepts. Airlift bioreactors are pneumatically agitated
class of bioreactors with unique mixing characteristics. The chapter
12 analyzes the advantages and disadvantages of external loop airlift
bioreactors in comparison to other types of airlift bioreactors.

Human multipotent mesenchymal stromal cells (hMSC) are quite

attractive for cell based therapies, but their low availability in tissues
(0.01-0.0005%) and the need for high doses (about 106 cells/Kg) for an
infusion necessitates the development of effective and low cost
technologies for in vitro expansion. The chapter 13 evaluates the
current hMSC expansion technologies, evaluating critically the
advantages of each one, and future perspectives for large scale clinical
grade hMSC production.

Carboxylic acids are important organic compounds in chemical,

food, and pharmaceutical industries. Conventionally, carboxylic acids
are prepared by any of the following methods: calcium hydroxide
precipitation method, adsorption, distillation, elctrodialysis, stripping,
reactive extraction, pertraction, pervaporation, and membrane
separations, etc. Many of these processes are expensive and each one
has its own benefits and limitations. Reactive extraction is one
promising alternative for conventional and other developing processes.
The chapter 14 discusses the concept and scope of reactive extraction
for recovery of carboxylic acids. The effects of various parameters such
as type of diluents and extractant, temperature, pH, substrate, salt,
back extraction and regeneration have also been examined.

The chapter 15 takes into account the significant progress in the

area of liquid membranes for the extraction of selected organic acids
xxii Biotechnology Vol. 12: Bioprocess Engineering

such as citric, lactic and acetic acids. The classification of liquid

membranes and the mechanisms involved in solute transport has been
discussed. The advantages and drawbacks of these membranes have
also been covered.

Lipase enzyme has immense biotechnological applications in

various industries such as food, dairy, detergents, textile, cosmetic,
leather, synthesis of fine chemicals, agrochemicals, beverage, oil-
processing and pulp and paper manufacturing. The chapter 16 covers
an overview of the means and ways of downstream processing of lipase
involving conventional purification techniques and recent trends in
novel processing techniques explored for the extraction and
purification of lipase.

The chemostat is an open bioreactor made up of a vessel with an

entry for the nutriment solution and an outlet for a mix of biomass
excess, residual nutriment and various substances, metabolites,
cellular fragments, extracellular polymeric substances. The chapter
17 aims to reveal the methods of optimising and also to widen the
field of microorganism cultures in chemostat.

Clavulanic acid (CA) biomolecule acts as a potentiator of betalactam

antibiotics by competitive inhibition of beta-lactamases. In the
production process of CA, the downstream processing deserves special
attention since up to 90% of the total production cost may be associated
with this stage only. The chapter 18 presents a mathematical model
for the adsorption of CA in a stirred tank reactor using different types
of hydrotalcites as adsorbents and evaluates adsorption coefficient,
film coefficient and effective diffusivity for the characterization of the
adsorption process.

Plants are most attractive hosts for economical production of

pharmaceutical products. Much effort has therefore been devoted to
efficiently producing recombinant antibodies (Abs) in plants and plant
cell suspensions. The chapter 19 looks into pros and cons of transgenic
plants as attractive cell factories for high yield and cost-effective
production of recombinant pharmaceutical proteins especially human
monoclonal antibodies.

A vast amount of glycerol is produced every year as a by-product of

biodiesel production. This glycerol can be converted into 1, 3-
propanediol (1, 3-PDO), which is a valuable raw material for
biopolymer industry. The chapter 20 contains a general overview on
Preface xxiii

bio-plastics and focuses on the use of novel bioreactor configurations

for the production of 1, 3-PDO.

Near infrared and Raman spectroscopy have developed as necessary

analytical tools for quality control in wide fields of biotechnology,
microbiology, toxicology, chemistry and others. The chapter 21 unlocks
the utility of Near infrared and Raman spectroscopy in biotechnology
through several case studies.

Pulp and paper industry is one among the world’s biggest industries
with strong influence on both global economy and ecology. The
application of biological methods for the solution of paper industry
problems is an area of growing research and development. The chapter
22 is devoted to applications of biotechnology in the pulp and paper
industry with specific discussion on wood pulping, enzymatic catalysis
in pulp bleaching, biotechnology in paper making and treatment of
pulp and paper effluents.

The productivity of cellulases enzymes may be increased by gene

cloning of encoding cellulases to enhance expression of these genes.
The gene encoding carboxymethylcellulase (CMCase) of Bacillus
subtilis subsp. subtilis A-53 isolated from seawater was cloned and
expressed in E. coli JM109. The chapter 23 investigates the optimal
conditions for cell growth and production of CMCase by Bacillus
subtilis subsp. subtilis A-53 and its recombinant Escherichia coli
JMB109/A-53.

The chapter 24 delves into evaluation of various lignocellulosic agro

wastes (paddy straw, coir pith, sugarcane bagassae and dried leaf
litter) for the enhanced production of extracellular cellulase and
xylanase enzymes adopting solid state fermentation with different
moisture level ranged from 0 to 50% by soil isolate of Trichidorma
harzianum. Maximum enzyme production was recorded in paddy
straw followed by sugarcane bagasse with 25% moisture content.

Microorganisms play a crucial role in producing a large variety of

biological products for agricultural, industrial and medical
applications. Computer controlled bioreactors are now being used on
a bigger scale to produce large quantities of amino acids, recombinant
proteins, antibiotics or viral vaccines. Mathematical modeling allows
the researchers to analyze and optimize the processing steps to
maximize yield and purity of the final product. These and several
other aspects of Bioprocess/Biochemical Engineering have been
xxiv Biotechnology Vol. 12: Bioprocess Engineering

included in this volume to help all the students, researchers and

scientists who wish to apply the knowledge of innovative tools of
biotechnology in the production of new value-added products from
biomass.

Shishir Sinha
J.N. Govil
 xxv

ISBN : 1-62699-027-1

Table of Contents

Foreword to the Series v

About the Editors vii
List of Contributors ix
About the Series xiii
Preface xix

1. Biogas Production: An Everlasting Source of Energy and 1

Resources
CHAYANIKA PUTATUNDA (INDIA)
2. Process Engineering Principles and Technological 13
Aspects of Synthesis Gas Production from Biomass
ANJIREDDY BHAVANAM, RAMA RAJU BAADHE AND R.C. SASTRY (INDIA)
3. Advances in Pretreatment Strategies of Biochemical 34
Conversion of Biomass
C. KARUNANITHY, K. MUTHUKUMARAPPAN AND
W.R. GIBBONS (USA)
4. Strategies for Reduced Enzyme Utilization in Biomass to 126
Ethanol Conversion with Specific Assessment for the Role
of Amphiphiles
ANAHITA D. ECKARD, KASIVISWANATHAN MUTHUKUMARAPPAN
AND WILLIAM GIBBONS (USA)

5. A Promising Strategy to Biorefine Oils: Enzymatic 153

Catalyzed Biodiesel Production and Development of
High-Valued Products
YUN-JUN YAN AND CHENG PENG (CHINA)
6. Sustainable Biobutanol is the Green Gasoline of the Future 180
BANAFSHEH MOHTASEBI, SARKAR BEGUM AND
YASER DAHMAN (CANADA)
xxvi Biotechnology Vol. 12: Bioprocess Engineering

7. Fermentation of Biomass: Coffee Pulp 213

EVANDRO GALVÃO TAVARES MENEZES, ISABELA COSTA GUIMARÃES
AND JOSÉ GUILHERME LEMBI FERREIRA ALVES (BRAZIL)

8. From Waste to Value-Added Products – Solid-State 223

Fermentation by White-Rot Fungi
MARINA TIŠMA, NATALIJA VELIC AND BRUNO ZELIC (CROATIA)
9. Interaction Between the Physical Properties of Cultivated 256
Substrate and Microorganism Growth in Solid-State
Fermentation
WANG LAN, MAO PENG, DUAN YINGYI AND CHEN
HONGZHANG (CHINA)
10. Microreactors-Think Big by Going Small 266
ANITA SALIC, ANA JURINJAK TUSEK AND BRUNO ZELIC (CROATIA)
11. Bioreactors for Tissue Engineering 292
SHALINI SINGH, RUPIKA SINHA, UTKARSH SINGH AND
PRADEEP SRIVASTAVA (INDIA)
12. Hydrodynamics of Pneumatically Agitated External Loop 306
Airlift Bioreactors
MIAN HAMOOD-UR-REHMAN, FARHAD EIN MOZAFFARI AND
YASER DAHMAN (CANADA)
13. Human Mesenchymal Stromal Cell Bioreactor Expansion 348
KAMILLA SWIECH, AMANDA MIZUKAMI, DIMAS TADEU COVAS
AND CLAUDIO ALBERTO TORRES SUAZO (BRAZIL)

14. Reactive Extraction of Carboxylic Acids 363

KAILAS L. WASEWAR (INDIA)
15. Downstream Processing of Organic Acids Involving 384
Liquid Membranes
B.S. CHANUKYA AND NAVIN K. RASTOGI (INDIA)
16. Ways and Means for the Downstream Processing of Lipase 408
SAIBAL BHOWAL, B.S. PRIYANKA, K.E. NANDINI AND NAVIN
K. RASTOGI (INDIA)
17. Metabolic Level Modelling Applied to Metabolites Cells 434
Production in a Chemostat
JACQUES THIERIE (BELGIUM)
18. Determination of Equilibrium and Mass-Transfer Para- 466
meters in a Batch Adsorption System: Mathematical
Table of Contents xxvii

Modeling of Clavulanic Acid Adsorption in

Hydrotalcites
MARCUS BRUNO SOARES FORTE, MARCIO A. MAZUTTI, ÉLEN
CRISTINA L. ELIAS, M ARIA ISABEL RODRIGUES AND
FRANCISCO MAUGERI FILHO (BRAZIL)
19. Biopharming and Bioprocessing of Plantibodies 481
SAJJAD KHANI, ABOLFAZL BARZEGARI AND
YADOLLAH OMIDI (IRAN, USA)
20. Biopolymers: Novel Bioprocess Configuration for 1,3- 520
Propanediol (1,3-PDO) Production
NURI AZBAR AND MINE GUNGORMUSLER (TURKEY)
21. Application of NIR and Raman Spectroscopy in 539
Biotechnology
MARZENA JAMRÓGIEWICZ (POLAND)
22. Biotechnology Applications in Pulp and Paper Industry 561
ANA P.M. TAVARES, ANA M.R.B. XAVIER AND DMITRY
V. EVTUGUIN (PORTUGAL)
23. Comparison of Optimal Conditions for Production of 582
Carboxymethylcellulase by Bacillus subtilis subsp. subtilis
A-53 and its Recombinant Escherichia coli JMB109/A-53
EUN-JUNG LEE, BO-HWA LEE, B O-KYUNG KIM AND
JIN-WOO LEE (KOREA)
24. Evaluation of Agro Wastes for the Enhanced Production 601
of Extracellular Cellulase and Xylanase by
Trichoderma harzianum
G. PRABAKARAN AND S. KARTHICK RAJA NAMASIVAYAM (INDIA)
Appendix-I: Table of Contents of Biotechnology Series 615
(Vols. 1 to 12)
Subject Index 631
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