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RSC Green Chemistry
Published on 30 November 2015 on | doi:10.1039/9781782624080-FP001
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Ames, Iowa, USA
Professor Andrzej Stankiewicz, Delft University of Technology, The Netherlands
Professor Peter Siedl, Federal University of Rio de Janeiro, Brazil
Titles in the Series:
1: The Future of Glycerol: New Uses of a Versatile Raw Material
2: Alternative Solvents for Green Chemistry
3: Eco-Friendly Synthesis of Fine Chemicals
4: Sustainable Solutions for Modern Economies
5: Chemical Reactions and Processes under Flow Conditions
6: Radical Reactions in Aqueous Media
7: Aqueous Microwave Chemistry
8: The Future of Glycerol: 2nd Edition
9: Transportation Biofuels: Novel Pathways for the Production of Ethanol,
Biogas and Biodiesel
10: Alternatives to Conventional Food Processing
11: Green Trends in Insect Control
12: A Handbook of Applied Biopolymer Technology: Synthesis, Degradation
and Applications
13: Challenges in Green Analytical Chemistry
14: Advanced Oil Crop Biorefineries
15: Enantioselective Homogeneous Supported Catalysis
16: Natural Polymers Volume 1: Composites
17: Natural Polymers Volume 2: Nanocomposites
18: Integrated Forest Biorefineries
19: Sustainable Preparation of Metal Nanoparticles: Methods and
Applications
20: Alternative Solvents for Green Chemistry: 2nd Edition
21: Natural Product Extraction: Principles and Applications
22: Element Recovery and Sustainability
23: Green Materials for Sustainable Water Remediation and Treatment
24: The Economic Utilisation of Food Co-Products
25: Biomass for Sustainable Applications: Pollution Remediation and
Energy
26: From C–H to C–C Bonds: Cross-Dehydrogenative-Coupling
27: Renewable Resources for Biorefineries
28: Transition Metal Catalysis in Aerobic Alcohol Oxidation
29: Green Materials from Plant Oils
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30: Polyhydroxyalkanoates (PHAs) Based Blends, Composites and
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31: Ball Milling Towards Green Synthesis: Applications, Projects, Challenges
32: Porous Carbon Materials from Sustainable Precursors
33: Heterogeneous Catalysis for Today’s Challenges: Synthesis, Characterization and Applications
34: Chemical Biotechnology and Bioengineering
35: Microwave-Assisted Polymerization
36: Ionic Liquids in the Biorefinery Concept: Challenges and Perspectives
37: Starch-based Blends, Composites and Nanocomposites
38: Sustainable Catalysis: With Non-endangered Metals, Part 1
39: Sustainable Catalysis: With Non-endangered Metals, Part 2
40: Sustainable Catalysis: Without Metals or Other Endangered Elements,
Part 1
41: Sustainable Catalysis: Without Metals or Other Endangered Elements,
Part 2
42: Green Photo-active Nanomaterials: Sustainable Energy and Environmental Remediation
43: Commercializing Biobased Products: Opportunities, Challenges,
Benefits, and Risks
44: Biomass Sugars for Non-Fuel Applications
45: White Biotechnology for Sustainable Chemistry
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White Biotechnology for
Sustainable Chemistry
Edited by
Maria Alice Z. Coelho
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Email:
Bernardo D. Ribeiro
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Email:
Published on 30 November 2015 on | doi:10.1039/9781782624080-FP001
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Published on 30 November 2015 on | doi:10.1039/9781782624080-FP007
Preface
White biotechnology can be regarded as applied biocatalysis with enzymes
and microorganisms, aiming at industrial production from bulk and fine
chemicals to food and animal feed additives. In turn, biocatalysis has many
attractive features in the context of sustainable chemistry: mild reaction conditions (at physiological pH and temperature), and environmentally compatible catalysts and solvents (often water) combined with high activities
and chemo-, regio- and stereoselectivity in multifunctional molecules. This
affords processes which are shorter, generate less waste and are, therefore,
both environmentally and economically more attractive than conventional
routes. The main contribution of this book will be the use of white biotechnology (enzymes, microorganisms and plant tissues) within the green
chemistry concept for: waste minimization, the use of alternative solvents
(supercritical fluids, pressurized gases, ionic liquids and micellar systems)
and energy sources (microwaves and ultrasound), besides providing more
sustainable approaches for the production of fine and bulk chemicals (aromas, polymers, pharmaceuticals and enzymes), such as the use of renewable
resources or agroindustrial residues, and biocatalyst recycling.
This text was driven by considering the concepts involved in both the subjects white biotechnology and sustainable chemistry, so that it could be possible to combine the knowledge obtained in each chapter herein presented.
In addition, a contribution from the industrial point of view is also presented
to demonstrate the feasibility of bioproduction systems. This last aspect can
be considered unique!
RSC Green Chemistry No. 45
White Biotechnology for Sustainable Chemistry
Edited by Maria Alice Z. Coelho and Bernardo D. Ribeiro
© The Royal Society of Chemistry 2016
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viii
Preface
We would like to thank all of the authors who agreed to participate in this
book project, giving the readers a broad spectrum on the state of the art,
since this book combines people from different parts of the world, as well as
providing a glance at Brazilian reality.
Maria Alice Z. Coelho and Bernardo D. Ribeiro
Published on 30 November 2015 on | doi:10.1039/9781782624080-FP009
Contents
Chapter 1 Principles of Green Chemistry and White Biotechnology
Bernardo Dias Ribeiro, Maria Alice Z. Coelho, and
Aline Machado de Castro
1.1 Green Chemistry: Could Chemistry be Greener?
1.2 White Biotechnology
1.3 Concluding Remarks
References
Chapter 2 Sustainability, Green Chemistry and White Biotechnology
Roger A. Sheldon
2.1 Introduction to Green Chemistry and Sustainability
2.2 Green Chemistry Metrics
2.3 Environmental Impact and Sustainability Metrics
2.4 The Role of Catalysis in Waste Minimisation
2.5 Solvents and Multiphase Catalysis
2.6 Green Chemistry and White Biotechnology
2.7 Green and Sustainability Metrics of White
Biotechnology
2.7.1 Fermentation processes
2.7.2 Enzymatic Production of an Atorvastatin
Intermediate
2.7.3 Enzymatic Synthesis of Sitagliptin
2.7.4 Enzymatic Production of Myristyl Myristate
2.8 White Biotechnology, Green Chemistry and the
Utilisation of Waste Biomass
2.9 Conclusions & Future Prospects
References
RSC Green Chemistry No. 45
White Biotechnology for Sustainable Chemistry
Edited by Maria Alice Z. Coelho and Bernardo D. Ribeiro
© The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org
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Chapter 3 Biocatalysis in Organic Media
A. Illanes
3.1 Enzyme Structure and Function
3.2 Enzymes and Biocatalysts
3.3 Enzyme Catalysis in Aqueous Media
3.4 Enzyme Biocatalysis in Non-Aqueous
(Non-Conventional) Media
3.4.1 Gases
3.4.2 Supercritical Fluids
3.4.3 Ionic Liquids
3.4.4 Semisolid Systems
3.4.5 Reactions Conducted at Very High Substrate
Concentration
3.5 Enzyme Biocatalysis in Organic Solvents
3.6 Enzymes as Catalysts for Organic Synthesis
3.7 Conclusions
References
Chapter 4 Microwave Assisted Enzyme Catalysis: Practice and
Perspective
Ganapati D. Yadav and Saravanan Devendran
4.1 Introduction
4.2 Enzyme Catalysis
4.3 Microwave Irradiation
4.3.1 Brief History of Microwave Technology
4.3.2 Microwave Principles
4.3.3 Interaction Between Microwave Irradiation
and Reaction Medium
4.3.4 Microwave Heating vs. Conventional Heating
4.3.5 Application of Microwaves in Enzymatic
Reactions – Green Chemistry Approach
4.4 Application to Different Industrially Relevant
Reactions
4.4.1 Microwave Assisted Enzymatic Hydrolysis
for Proteomics
4.4.2 Application of Microwave Irradiation for
Enzyme Catalyzed Biodiesel Production
4.4.3 Application of Microwave Irradiation to
Enzyme Catalyzed Polymer Synthesis
4.4.4 Application of Microwave Irradiation for
Enzyme Catalyzed Reactions in the
Chemical Industry
4.4.5 Application of Microwaves for Enzyme
Catalyzed Reactions in the Food and
Cosmetics Industries
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4.4.6 Application of Microwave Heating for
Enzyme Catalyzed Reactions in the
Pharmaceutical Industry
4.4.7 Separation of Racemic Compounds
4.4.8 Application of Microwaves to Enzyme
Immobilization
4.5 Kinetic Models and Their Critical Analysis
4.6 Conclusions
Nomenclature
References
Chapter 5 Lipase-Catalyzed Reactions in Pressurized Fluids
Raquel Loss, Lindomar Lerin, José Vladimir de Oliveira,
and Débora de Oliveira
5.1 Introduction
5.2 Behavior of Lipases in Supercritical and
Compressed Fluids
5.2.1 Effect of Nature of Solvent
5.2.2 Effects of Changing Pressure
5.2.3 Effects of Changing Temperature
5.2.4 Effect of Changing Water Content
5.2.5 Water Activity (aw)
5.2.6 Effect of Pressurization and
Depressurization
5.3 Lipase-Catalyzed Reactions in Supercritical
and Compressed Fluids
5.3.1 Esterification
5.3.2 Transesterification
5.3.3 Interesterification
5.3.4 Hydrolysis
5.4 Conclusions
References
Chapter 6 Biocatalysis in Ionic Liquids
Bernardo Dias Ribeiro, Ariane Gaspar Santos,
and Isabel M. Marrucho
6.1 Ionic Liquids
6.2 Enzymes in Ionic Liquids
6.2.1 Lipases, Proteases and Esterases
6.2.2 Glycosidases
6.2.3 Other Enzymes
6.3 Whole-Cell Processes in Ionic Liquids
6.3.1 Toxicity Toward Microorganisms
6.3.2 Whole-Cell Biocatalysis
References
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Chapter 7 Biocatalysis in Micellar Systems
Adelaide Braga and Isabel Belo
7.1 Introduction
7.1.1 Biocatalysis
7.1.2 Micellar Systems
7.2 Oil-in-Water Systems
7.2.1 Emulsion Characterization
7.2.2 Enzyme Catalysis
7.2.3 Whole-Cell Biotransformations
7.3 Water-in-Oil Systems
7.3.1 Influence of Phase Composition
7.3.2 Enzymatic Reactions
7.3.3 Immobilization of Reverse Micelles
7.4 Concluding Remarks
References
Chapter 8 Green Downstream Processing in the Production
of Enzymes
P. F. F. Amaral and T. F. Ferreira
8.1 Introduction
8.2 Initial Separation Steps for Enzyme Recovery
8.3 Concentration Steps in Enzyme Downstream
Processing
8.3.1 Precipitation
8.3.2 Membrane Separation
8.4 Purification Technologies for Enzymes
8.4.1 Chromatography
8.4.2 Biphasic Systems
8.5 Conclusions
Acknowledgements
References
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Chapter 9 Lipases in Enantioselective Syntheses: Evolution of
Technology and Recent Applications
207
Denise Maria Guimarães Freire, Angelo Amaro Theodoro
da Silva, Evelin de Andrade Manoel, Rodrigo Volcan Almeida,
and Alessandro Bolis Costa Simas
9.1 Introduction
9.2 Lipase-Catalyzed Enantioselective Syntheses
9.2.1 Classical Kinetic Resolution
9.2.2 Deracemization Processes
9.2.3 Enantioselective Desymmetrizations
9.3 Medium Engineering
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9.4 Immobilization of Lipases
9.4.1 Brief Background
9.4.2 Immobilization Protocols
9.5 Tailor-Made Lipases: Improving the
Enantioselectivity
9.6 Reactor Configuration
9.7 The Use of Ionic Liquids
References
Chapter 10 Redox Biotechnological Processes Applied to
Fine Chemicals
J. Augusto R. Rodrigues, Paulo J. S. Moran,
Bruna Z. Costa, and Anita J. Marsaioli
10.1 Introduction
10.2 Redox Enzymes
10.3 Oxidation Reactions
10.3.1 Hydroxylation
10.3.2 Epoxidation
10.3.3 Baeyer–Villiger Oxidation
10.3.4 Sulfide Oxidation
10.3.5 Lipase-Mediated Oxidation
10.4 Reduction Reactions
10.4.1 Reduction of Diketones
10.4.2 Reduction of α-Methyleneketones
10.4.3 Reduction of α-Haloketones and
α-Haloenones
10.5 Conclusions
Acknowledgements
References
Chapter 11 Production of Polymers by White Biotechnology
S. Shoda, A. Kobayashi, and S. Kobayashi
11.1 Introduction – Production of Polymers via
Conventional Chemical Processes
11.2 Monomer Production by White Biotechnology
11.2.1 Microbial Production of Monomers
11.2.2 Monomer Synthesis by Enzymatic
Degradation of Naturally Occurring
Polymers
11.2.3 Enzymatic Conversion of Vinyl Monomers
11.3 Polymer Production by White Biotechnology
11.3.1 General Aspects
11.3.2 Polymer Production by Microorganisms
(Table 11.2)
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11.3.3 Polymer Production via Biosynthetic
Pathways In vitro
11.3.4 Enzymatic Polymerization
11.4 Future Prospects
References
Chapter 12 Production of Aroma Compounds by White
Biotechnology
Juliano Lemos Bicas, Gustavo Molina, Francisco
Fábio Cavalcante Barros, and Gláucia Maria Pastore
12.1 Introduction
12.2 Methods for Producing Aroma Compounds
12.3 Why Use White Biotechnology to Produce
Aroma Compounds?
12.4 Examples of Aroma Compounds Produced
Through White Biotechnology
12.4.1 Background and Overview: Processes,
Advantages and Developments
12.4.2 Products Obtained—An Industrial
Perspective
12.4.3 Production of Aroma Compounds in
Bioreactors
12.5 Green Chemistry in the Production of Aroma
Compounds
12.5.1 Alternative Solvents
12.5.2 Alternative Extraction Methods
12.5.3 Alternative Substrates
12.6 Concluding Remarks
References
Chapter 13 Biotransformation Using Plant Cell Culture Systems and
Tissues
Bernardo Dias Ribeiro, Evelin Andrade Manoel, Claudia
Simões-Gurgel, and Norma Albarello
13.1 Biotransformation and Green Chemistry
13.2 Plant Cell Cultures
13.3 Use of Plant Cell Cultures in Biotransformation
13.3.1 Biotransformation Using Cell
Immobilization
13.3.2 β-Cyclodextrins in Biotransformation
13.4 Use of Whole or Parts of Plants in
Biotransformation
13.4.1 Phytoremediation
13.4.2 Biosensors
13.4.3 Reduction
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13.4.4 Hydrolysis
13.4.5 Oxidation
eferences
R
Chapter 14 Development of Processes for the Production of
Bulk Chemicals by Fermentation at Industrial
Scale – An Integrated Approach
Jørgen Magnus
14.1 Introduction
14.1.1 The Potential of White Biotechnology for
the Production of Bulk Chemicals
14.1.2 Setup of a Development Project
14.2 Steering the Direction of the Development
Project
14.2.1 The Three Typical Main Business Drivers
in Large Scale Bioproduction
14.2.2 The Three Typical Main Parameters for
Reducing the Cost of Production
14.2.3 Alignment with Business Drivers
14.3 Strain Development
14.3.1 Search for Natural Producers
14.3.2 Metagenomics
14.3.3 Host Strain Selection
14.3.4 Random Mutagenesis
14.3.5 Screening
14.3.6 Metabolic Engineering
14.3.7 Evolutionary Engineering
14.3.8 Protein Engineering
14.4 Process Technology Development
14.4.1 Conceptual Design
14.4.2 Raw Materials
14.4.3 Fermentation
14.4.4 Product Recovery
14.4.5 Purification
14.5 The Integrated Approach: Developing
Microbiology and Process Technology
in Parallel
14.5.1 Product Inhibition
14.5.2 Fermentation Operating Mode
14.5.3 Unit Operations in the Downstream Part
of the Plant
14.5.4 Holistic Understanding of Biology
and Process Technology
14.6 Conclusions
Acknowledgements
References
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Chapter 15 Trends and Perspectives in Green Chemistry and White
Biotechnology
Bernardo Dias Ribeiro and Maria Alice Zarur Coelho
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15.1 Ultrasound
15.2 Fluorous Solvents
15.3 Aphrons
15.4 Glycols
15.4.1 Glymes
15.4.2 Liquid Polymers
15.5 Alkyl Carbonates
15.6 Other Applications
15.6.1 Tunable Solvents
15.6.2 Biodesalination
15.6.3 Nanotechnology
References
Subject Index
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Chapter 1
Principles of Green Chemistry
and White Biotechnology
Bernardo Dias Ribeiroa, Maria Alice Z. Coelhoa, and
Aline Machado de Castro*b
a
Biochemical Engineering Department, School of Chemistry, Federal
University of Rio de Janeiro, Brazil; bBiotechnology Division, Research
and Development Center, PETROBRAS, Brazil
*E-mail:
1.1 Green Chemistry: Could Chemistry be Greener?
Since the Second World War, world industrialization has been accelerated
without caring about its effects on the environment, and peoples’ safety and
health. This has led to increased global warming, depletion of the ozone protective layer which protects against harmful UV radiation, contamination of
land and waterways due to the release of toxic chemicals by industry, and
the reduction of nonrenewable resources such as petroleum. Nevertheless,
there is a growing awareness amongst end-users of the risks that chemicals
are often associated with, and of the need to dissociate themselves from any
chemical in their supply chain that is recognized as being hazardous.1,2
In the 1990s, the idea of developing new or improving existing chemical
products and processes to make them less hazardous to human health and
the environment had already been contemplated. Initially, in 1991, the Office
of Pollution Prevention and Toxics (OPPT) of the United States launched a
research grant program named “Alternative Synthetic Pathways for Pollution
RSC Green Chemistry No. 45
White Biotechnology for Sustainable Chemistry
Edited by Maria Alice Z. Coelho and Bernardo D. Ribeiro
© The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org
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2
Chapter 1
Prevention”. In 1993, the program was expanded to include other topics, such
as greener solvents and safer chemicals, and was renamed “Green Chemistry”.3
Nowadays, green chemistry has as main objective the promotion of innovative chemical technologies that reduce or eliminate the use or generation
of hazardous substances in the design, manufacture, and use of chemical
products, meaning the use of more environmentally acceptable chemical
processes and products.1,4,5
In 1998, Paul Anastas and Warner announced a set of 12 principles as a useful guide for designing environmentally benign products and processes or to
evaluate already existing processes,4 and in 2003, this promulgated another
12 principles on Green Engineering, which correlates Chemical Engineering
with Green Chemistry, aiming to achieve sustainability (in the three dimensions: ecological, economic and social), maximize efficiency, minimize waste
and increase profitability,5,6 as shown in Table 1.1.
To achieve greener chemical processes, besides the more intensive use of
renewable feedstocks, several technologies have been developed, some old
and some new, which are becoming proven clean technologies, such as the
use of alternative solvents (supercritical fluids, ionic liquids, fluorous liquids), non-thermal energetic sources (microwaves, ultrasounds, electrical
fields, solar energy), environmentally-friendly separation processes such as
membranes (ultrafiltration, nanofiltration and pervaporation), and biological catalysts, such as micro-organisms and enzymes, allowing the creation of
more energy-efficient processes.2,4,7
1.2 White Biotechnology
Biotechnology is a very broad area which embraces five main sectors:
Blue Biotechnology – Also known as Marine and Fresh-water Biotechnology,8
this sector includes bioprospecting in marine environments and the use of
molecular biology and microbial ecology tools in marine organisms.9
Green Biotechnology – Is the biotechnology for agricultural applications.
As input, plants are genetically modified to have resistance to insects or diseases, and as outputs, plants present improved agronomic behavior (yield,
withstanding environmental stress) and can be used as green factories.10
Red Biotechnology – Is the area that focuses on humans and is used to
develop alternative solutions to medical problems and issues from diagnosis to therapy.11 Also named Pharmaceutical Biotechnology.12
White Biotechnology – Related to the use of living cells (yeasts, molds,
bacteria, plants) and enzymes to synthesize products at industrial scale.
Also known as Industrial Biotechnology.13
Yellow Biotechnology – Also known as Insect Biotechnology, this emerging field in applied entomology covers the use of insects in drug discovery,
their study for plant defense, and the use of insects as a source of enzymes
and cells for biotransformations and as a source of biosensors for online
detection of compounds at industrial scale. Therefore, this area interacts
with White and Green Biotechnology areas.14
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Principles of Green Chemistry and White Biotechnology
3
Table 1.1 Comparative
framework of principles of Green Chemistry and Green
Engineering.
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Green Chemistry
Green Engineering
1. Prevention: It is better to prevent
waste than to treat or clean up waste
after it has been created
1. Inherent rather than circumstantial:
Designers need to strive to ensure that
all materials and energy inputs and
outputs are as inherently
nonhazardous as possible
2. Atom economy: Synthetic methods
2. Prevention instead of treatment: It is
should be designed to maximize the
better to prevent waste than to treat or
incorporation of all materials used in
clean up waste after it is formed
the process into the final product
3. Design for separation: Separation and
3. Less hazardous chemical syntheses:
purification operations should be
Wherever practicable, synthetic
designed to minimize energy
methods should be designed to use
consumption and materials use
and generate substances that present
low or no toxicity to human health
and the environment
4. Designing safer chemicals: Chemical 4. Maximize efficiency: Products,
products should be designed to effect
processes, and systems should be
their desired function while
designed to maximize mass, energy,
minimizing their toxicity
space, and time efficiency
5. Output-pulled versus input-pushed:
5. Safer solvents and auxiliaries: The
Products, processes, and systems
use of auxiliary substances (e.g., solshould be “output pulled” rather than
vents, separation agents, etc.) should
“input pushed” through the use of
be made unnecessary whenever
energy and materials
possible and should be innocuous
when used
6. Conserve complexity: Embedded
6. Design for energy efficiency: Energy
entropy and complexity must be
requirements of chemical processes
viewed as an investment when making
should be recognized for their
design choices on recycle, reuse, or
environmental and economic impacts
beneficial disposition
and should be minimized. If possible,
synthetic methods should be
conducted at ambient temperature
and pressure
7. Durability rather than immortality:
7. Use of renewable feedstocks: A raw
Targeted durability, not immortality,
material or feedstock should be
should be a design goal
renewable rather than depleting
whenever technically and
economically practicable
8. Meet need, minimize excess: Design
8. Reduce derivatives: Unnecessary
for unnecessary capacity or
derivatization (use of blocking groups,
capability (e.g., “one size fits all”)
protection/deprotection, temporary
solutions should be considered a
modification of physical/chemical
design flaw
processes) should be minimized or
avoided if possible, because such
steps require additional reagents and
can generate waste
9. Catalysis: Catalytic reagents (as
9. Minimize material diversity: Material
selective as possible) are superior to
diversity in multicomponent products
should be minimized to promote
stoichiometric reagents
disassembly and value retention
(continued)
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Chapter 1
4
Table 1.1 (continued)
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Green Chemistry
Green Engineering
10. Integrate material and energy flows:
10. Design for degradation: Chemical
Design of products, processes, and
products should be designed so that
systems must include integration
at the end of their function they
and interconnectivity with available
break down into innocuous degradaenergy and materials flows
tion products and do not persist in
the environment
11. Design for commercial “afterlife”:
11. Real-time analysis for pollution
Products, processes, and systems
prevention: Analytical methodoloshould be designed for performance
gies need to be further developed to
in a commercial “afterlife”
allow for real-time, in-process monitoring and control prior to the formation of hazardous substances
12. Renewable rather than depleting:
12. Inherently safer chemistry for
Material and energy inputs should be
accident prevention: Substances and
renewable rather than depleting
the form of a substance used in a
chemical process should be chosen
to minimize the potential for chemical accidents, including releases,
explosions, and fires
Enzymes are classified into 6 classes (as described below) and they receive
a classification number, based on their class, subclass and the specific chemical groups participating in the reaction.15
1.Oxidoreductases: All enzymes catalyzing oxidoreduction reactions
belong to this class. The substrate that is oxidized is regarded as a
hydrogen donor.
2.Transferases: Transferases are enzymes which catalyze the transfer of
a group, e.g. a methyl group or a glycosyl group, from one compound
(generally regarded as a donor) to another compound (generally
regarded as an acceptor).
3.Hydrolases: These enzymes catalyze the hydrolytic cleavage of C–O,
C–N, C–C and some other bonds, including phosphoric anhydride
bonds.
4.Lyases: Enzymes catalyzing the cleavage of C–C, C–O, C–N, and other
bonds by elimination, leaving double bonds or rings, or conversely adding groups to double bonds.
5.Isomerases: These enzymes catalyze geometric or structural changes
within one molecule.
6.Ligases: Enzymes that catalyze the linkage of two molecules, coupled with the hydrolysis of a diphosphate bond in ATP or a similar
triphosphate.
White biotechnology is a continuously growing sector, with an average
annual growth in the period 2007–2012 of 10.4%.16 The industry embraces
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Principles of Green Chemistry and White Biotechnology
5
the large-scale production of molecules for several sectors, such as: fertilisers
and gases, organic chemicals, polymers and fibers, agrochemicals, adhesives
and sealants, paints and coatings, food additives, detergents, cosmetics, active
pharma ingredients,17 as well as the enzymes involved in the production of final
molecules, such as in textiles processing,18 beverages, foods, biofuels19 and pulp
and paper.20
The worldwide market for white biotechnology involved transactions on
the order of €92 billion in 2010. In late 2011, it was estimated that sales
would increase to around €228 billion in 2015 and to around €515 billion
in 2020.17 Specifically, in the field of enzyme catalysis, the global estimated
market size of enzymes in 2010 was USD2.82 billion, with food and feed
being the major end-user market (USD1.19 billion) and textiles the fastest growing end-user market (4.99%).20 In 2010, carbohydrases (hydrolases
acting on carbohydrates) were the fastest growing product segment (7.6%),
and proteases alone accounted for 48% (USD1.35 billion) of the total
enzyme market.20 Additionally, lipases, a group of enzymes of paramount
importance in green processes, have also shown growth in their market,
which increased from USD235 million in 2001 to USD429 million in 2010,20
mainly focused on the production of pharmaceuticals, foods and beverages
and cleaning products.21 The projected global market for lipases in 2015 is
USD634 million.20
Enzyme-catalyzed reactions are indicated to be very promising to meet
green chemistry criteria. In the context of the principles of green chemistry,
catalysts as a whole provide not only a solution for the problem of waste, but
additionally create more energy efficient and less raw material consuming
processes. Biocatalysts, specifically, present some positive points: they can
act as non-toxic catalysts; they generally operate with high selectivity, yielding
high product purity; they operate under moderate reaction conditions at near
ambient temperature, pressure and pH, thus resulting in reduced energy consumption; the reaction medium is commonly aqueous, which per se is considered
non-toxic; biocatalysts have the potential to prevent high consumption of metals
and organic solvents; as natural catalysts, enzymes can be considered as
renewable catalysts.22 It should be highlighted, however, that even for biocatalytic
processes, each procedure must be evaluated for its environmental friendliness
and economic feasibility.23 Some important remarks on the use of biocatalysts
in industrial processes are given in Table 1.2.
1.3 Concluding Remarks
With the above considerations, the interaction between green chemistry and
white biotechnology will have a relevant role in the construction of a new
industrial concept based on technologies (described herein in this book)
that, in the near future, will become the basis of a new paradigm. Some
examples of the development of sustainable production processes based on
such principles can be seen nowadays all over the world. They can help to
save energy and the environment.
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Chapter 1
6
Table 1.2 Important
remarks about biocatalysis in green chemistry (adapted from
ref. 23).
Published on 30 November 2015 on | doi:10.1039/9781782624080-00001
Remarks
Critical analysis
1. Use of water as green Some organic compounds present low solubility in water;
solvent
downstream processing of aqueous solutions often
demands extraction with organic solvents
2. Enzyme engineering Promising field which, however, requires a long time for
development from the idea to implementation at an
industrial scale; new high throughput methods can
accelerate development
3. Productivity
Considering that a minimum volumetric productivity of
0.1 g L−1 h−1 and a minimum final product concentration of 1 g L−1 is acceptable for implementation at an
industrial scale, process optimization in terms of the
increase of the substrate concentration and its feeding
form and the stability of the biocatalyst is required
4. Low substrate
Due to enzyme inhibition problems, low substrate
concentration
concentrations are commonly adopted, resulting
in oversized reactors and inefficient downstream
processing
5. Potential as an
Although biocatalytic processes are often greener than
alternative process
chemical ones, for industry, ecological reasons are not the
only subjects to be addressed for the replacement of an
existing process. On the other hand, sometimes there are
no chemical alternatives to a biotechnological pathway
6. Pharmaceutical
The combination of chemical and biocatalytic steps is the
development
most promising path for specific and functionalized
products; for the obtainment of chiral molecules, if the
separation of racemates is complex and not reliable,
enantioselective biotransformations should be used
7. Price of the catalyst The cost contribution of the biocatalyst is strongly related
to the value of the products. They may vary from
USD 0.05 kg−1
product (bulk chemicals) to up to USD
24
10 kg−1
product (pharma products)
8. Downstream
Aqueous solutions, commonly used in biotransformaprocessing
tions, require a significant amount of solvent for
product isolation; strategies such as in situ product
removal and engineering of solvent-tolerant enzymes
could overcome this issue
9. Use of ionic liquids Functional fluids often improve substrate solubility, but
incur additional expense in downstream processing;
more information about their toxicity is needed
10. Substrate spectrum Although specificity is claimed to be one advantage of
for biocatalysis
enzymes over chemical catalysts, some biocatalysts,
such as lipases, present substrate versatility and diverse
catalytic function
Especially concerning to Brazil, it is generally recognized that the country
has competitive advantages related to: the available area and favorable climate; the efficient production of biomass (sugar cane, eucalyptus, soy, etc.);
the pioneering production of biofuels on a large scale; the productivity of
agriculture which grew at twice the global average from 2001 to 2009, and it
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Principles of Green Chemistry and White Biotechnology
7
is the country with the highest biodiversity in the world, through the multiplicity of species and habitats.
Nevertheless, improvement in bioprocess efficiency needs considerable
effort before bioprocesses can be considered a serious alternative to petrochemical industrial processes. Challenges related to the conversion of sugars
contained in biomass into the required compounds as effectively as possible
will lead to new biocatalyst characteristics, as well as novel operation strategies.
References
1.C. A. M. Afonso and J. G. Crespo, Green Separation Processes, Wiley-VCH
Verlag, Weinheim, Germany, 2005, pp. 3–19.
2.M. Doble and A. K. Kruthiventi, Green Chemistry and Engineering, Academic Press, San Diego, USA, 2007, pp. 1–23.
3. accessed 23
October 2012.
4.J. García-Serna, L. Pérez-Barrigón and M. J. Cocero, Chem. Eng. J., 2007,
133, 7.
5.J. A. Tao and R. Kazlauskas, Biocatalysis for Green Chemistry and Chemical
Process Development, John Wiley & Sons, Hoboken, New Jersey, 2011, pp.
3–28.
6.P. T. Anastas and J. B. Zimmerman, Environ. Sci. Technol., 2003, 37(5),
94A.
7.J. Clark and D. Macquarrie, Handbook of Green Chemistry and Technology,
Blackwell Science, Londres, 2002, pp. 1–26.
8.European Commission, />biotechnology/research/marine_fresh/index_en.htm, accessed 26 January
2013.
9.Bigelow, accessed 26 January 2013.
10.P. Oakley, 2005, />conversions:/publishdownload/content/investor-relations/calendar/
images/050831/Presentation_Oakley_Biotechl.pdf, accessed 26 January
2013.
11.BIO NRW, accessed 26 January 2013.
12.Linde, accessed 26
January 2013.
13.G. Frazzetto, EMBO Rep., 2003, 4(9), 835.
14.A. Vilcinskas, Yellow Biotechnology II – Insect Biotechnology in Plant Protection and Industry, Springer, Dordrecht, 2013, pp. v–vi.
15.IUBMB, Last update November 2012, />iubmb/enzyme/, accessed 26 January 2013.
16.IBIS World, Oct 2012, accessed 26 January 2013.
17.G. Festel, C. Detzel and R. Maas, J. Commer. Biotechnol., 2012, 18(1), 11.
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8
Chapter 1
18.Europabio., 2003, www.europabio.org, accessed 26 January 2013.
19.B. Sarrouh, T. M. Santos, A. Miyoshi, R. Dias and V. Azevedo, J. Bioprocess.
Biotech., 2012, S4, 002.
20.Global Industry Analysts, Inc., 2011, available by purchase from www.
strategyR.com.
21.Freedonia, 2010, available by purchase from edoniagroup.
com/DocumentDetails.aspx?DocumentId=509396.
22.R. Wohlgemuth, Curr. Opin. Biotechnol., 2010, 21, 713.
23.S. Wenda, S. Illner, A. Mell and U. Kragl, Green Chem., 2011, 13, 3007.
24.P. Tufvesson, J. Lima-Ramos, M. Nordblad and J. M. Woodley, Org. Process
Res. Dev., 2011, 15, 266.
Published on 30 November 2015 on | doi:10.1039/9781782624080-00009
Chapter 2
Sustainability, Green
Chemistry and White
Biotechnology
Roger A. Sheldon*a
a
Department of Biotechnology, Delft University of Technology, Netherlands
*E-mail: ,
2.1 Introduction
to Green Chemistry and
Sustainability
The roots of industrial organic synthesis can be traced back to the preparation of the first synthetic dye, mauveine (aniline purple) by Perkin in 1856.1
This serendipitous discovery (Perkin’s goal was the synthesis of the antimalarial drug, quinine) marked the advent of the synthetic dyestuffs industry based on coal tar, a waste product from steel manufacture. The modern
pharmaceutical and allied fine chemical industries evolved as spin-offs of
this industry. The target molecules were initially relatively simple, but in the
ensuing decades they became increasingly complicated, as exemplified by
the introduction of semi-synthetic beta-lactam antibiotics and steroid hormones in the 1940s and 1950s. To meet this and subsequent challenges,
synthetic organic chemists have developed increasingly sophisticated methodologies. However, many of these time-honoured and widely applied synthetic methodologies were developed at a time when the toxic properties of
RSC Green Chemistry No. 45
White Biotechnology for Sustainable Chemistry
Edited by Maria Alice Z. Coelho and Bernardo D. Ribeiro
© The Royal Society of Chemistry 2016
Published by the Royal Society of Chemistry, www.rsc.org
9
