Renewable Raw Materials E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 438

Veröffentlichungsjahr: 2011

Beschreibung

One of the main challenges facing the chemical industry is the transition to sustainable operations. Industries are taking initiatives to reduce resource intensities or footprints, and by adopting safer materials and processes. Such efforts need to be supported by techniques that can quantify the broad economic and environmental implications of industrial operations, retrofi t options and provide new design alternatives. This contemporary overview focuses on cradle-to-grave life cycle assessments of existing or conceptual processes for producing valueadded fuels, chemicals, and/or materials from renewable agricultural residues, plant-derived starches and oils, lignocellulosic biomass, and plant-based industrial processing wastes. It presents the key concepts, systems, and technologies, with an emphasis on new feedstocks for the chemical industry. Each chapter uses common themes of specifi c raw materials, thus forming a natural progression throughout the book. The result is coverage from a wide range of perspectives, emphasizing not only the technical issues but also considering the market place and socio-economic aspects.

Leseprobe

Table of Contents

Cover

Related Titles

Title page

Copyright page

List of Contributors

1 Introduction to Renewable Resources in the Chemical Industry

2 Plants as Bioreactors: Production and Use of Plant-Derived Secondary Metabolites, Enzymes, and Pharmaceutical Proteins

2.1 Introduction

2.2 Renewable Resources in the Chemical Industry

2.3 Fine Chemicals and Drugs

2.4 Plant-Made Pharmaceuticals

3 World Agricultural Capacity

3.1 Petrochemicals Today

3.2 Renewable Chemicals

3.3 Agricultural Production

3.4 Supplying the Chemical Industry

3.5 Summary

4 Logistics of Renewable Raw Materials

4.1 Introduction

4.2 Determining Factors for the Logistics of Industrial Utilization Chains for Renewable Raw Materials

4.3 Processing Steps of Renewable Raw Material Logistic Chains

4.4 Design and Planning of Renewable Raw Material Logistic Chains

4.5 Summary and Conclusions

5 Existing Value Chains

5.1 Industrial Biotechnology Today – Main Products, Substrates, and Raw Materials

5.2 White Biotechnology – Future Products from Today’s Raw Materials?

5.3 Effects of Feedstock and Process Technology on the Production Cost of Chemicals

5.4 New Raw Materials for White Biotechnology

5.5 Case Studies: Lignocellulose as Raw Material and Intermediates

5.6 Case Studies: “SCOs” as Raw Material and Intermediate

5.7 Conclusions

6 Future Biorefineries

6.1 Introduction

6.2 Current and Future Outlook for Biofuels

6.3 Chemicals from Renewable Resources

6.4 The Role of Clean Technologies in Biorefineries

6.5 The Size of Future Biorefineries

6.6 Conclusions

7 Economic and Social Implications of the Industrial Use of Renewable Raw Materials

7.1 Introduction

7.2 Biorefinery Industry and the Development of EU Rural Areas

7.3 From Analytic to Systemic Modeling Methodology of the Biorefinery Industry

7.4 Stakeholders’ Perceptions of Biorefinery in Rural Areas: Issues and Lessons from the South of Italy

7.5 Concluding Remarks

Acknowledgments

8 Biobased Products – Market Needs and Opportunities

8.1 Introduction

8.2 Definition

8.3 Basic Technology for the Conversion of Renewable Raw Materials

8.4 Classes of Bioproducts

8.5 Current Status

8.6 Outlook and Perspectives

9 Life-Cycle Analysis of Biobased Products

9.1 Introduction: Why Life-Cycle Analysis of Biobased Products?

9.2 The Methodological Framework of LCA

9.3 Specific Methodological Aspects for LCA for Biobased Products

9.4 LCA Studies for Biobased Products: Major Findings and Insights

9.5 Conclusions

10 Conclusion

Index

Related Titles

Soetaert, W., Vandamme, E. J. (eds.)

Industrial Biotechnology

Sustainable Growth and Economic Success

2010

Hardcover

ISBN: 978-3-527-31442-3

Soetaert, W., Vandamme, E. (eds.)

Biofuels

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ISBN: 978-0-470-02674-8

Deublein, D., Steinhauser, A.

Biogas from Waste and Renewable Resources

An Introduction

2008

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ISBN: 978-3-527-31841-4

Wengenmayr, R., Bührke, T. (eds.)

Renewable Energy

Sustainable Energy Concepts for the Future

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ISBN: 978-3-527-40804-7

The Editors

Prof. Dr. Roland Ulber

TU Kaiserslautern, Maschinenb.

AG Bioverfahrenstechnik,Geb 44

Gottlieb-Daimler-Str.

67663 Kaiserslautern

Germany

Dr. Dieter Sell

DECHEMA e.V.

Bioverfahrenstechnik

Theodor-Heuss-Allee 25

60486 Frankfurt

Germany

Prof. Dr. Thomas Hirth

Fraunhofer Institut für

Grenzflächen u. Bioverf. IGB

Nobelstr. 12

70569 Stuttgart

Germany

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ISBN: 978-3-527-32548-1

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List of Contributors

Rainer Busch

T+I Consulting

Bismarckstraße 15

76530 Baden-Baden

Germany

James Clark

University of York

Green Chemistry Centre of Excellence

YO10 5DD, York

United Kingdom

Dorothea Ernst

Karlsruhe Institute of Technology

Faculty of Chemical and Process Engineering

76128 Karlsruhe

Germany

Magnus Fröhling

Karlsruhe Institute of Technology (KIT)

Institute for Industrial Production

Hertzstraße 16

76187 Karlsruhe

Germany

Bernward Garthoff

Cluster BIO.NRW

Merowingerplatz 1

40225 Düsseldorf

Germany

Thomas Hirth

IGVT der Universität Stuttgart und Fraunhofer-Institut für Grenzflächen und Bioverfahrenstechnik

Institut für Grenzflächenverfahrenstechnik

Nobelstrasse 12

70569 Stuttgart

Germany

John K. Hughes

The Food and Environment Research Agency

Sand Hutton

YO41 1LZ, York

United Kingdom

Abbas Kazmi

University of York

Green Chemistry Centre of Excellence

YO10 5DD, York

United Kingdom

Antonio Lopolito

University of Foggia

Department of Production and Innovation in Mediterranean Agriculture and Food Systems (PrIME)

71100 Foggia

Italy

Jörn-Christian Meyer

Karlsruhe Institute of Technology (KIT)

Institute for Industrial Production

Hertzstraße 16

76187 Karlsruhe

Germany

Peter C. Morris

School of Life Sciences

Heriot-Watt University

Riccarton, Edinburgh EH14 4AS

UK

Kai Muffler

TU Kaiserslautern

Lehrgebiet Bioverfahrenstechnik

Gottlieb-Daimler-Str. 44

67663 Kaiserslautern

Germany

Anke Neumann

Karlsruhe Institute of Technology

Faculty of Chemical and Process Engineering

76128 Karlsruhe

Germany

Pasquale Pazienza

University of Foggia

Department of Economics

Mathematics and Statistics (SEMS)

71100 Foggia

Italy

Maurizio Prosperi

University of Foggia

Department of Production and Innovation in Mediterranean Agriculture and Food Systems (PrIME)

71100 Foggia

Italy

Georg Schaub

Karlsruhe Institute of Technology

Faculty of Chemical and Process Engineering

76128 Karlsruhe

Germany

Liselotte Schebek

Technische Universität Darmstadt

Fachbereich Bauingenieurwesen und Geodäsie (FB 13)

Fachgebiet Industrielle Stoffkreisläufe

Insitut WAR

Petersenstr. 13

64287 Darmstadt

Germany

Forschungszentrum Karlsruhe GmbH

Institut für Technikfolgenabschätzung und Systemanalyse

Zentralabteilung Technikbedingte Stoffströme (ITAS-ZTS)

76021 Karlsruhe

Germany

Frank Schultmann

Karlsruhe Institute of Technology (KIT)

Institute for Industrial Production

Hertzstraße 16

76187 Karlsruhe

Germany

Ines Schulze

Karlsruhe Institute of Technology

Faculty of Chemical and Process Engineering

76128 Karlsruhe

Germany

Jörg Schweinle

Johann Heinrich von Thünen-Institute (vTI)

Institute of Forest Based Sector Economics

Federal Research Institute for Rural Areas

Forestry and Fisheries

21002 Hamburg

Germany

Dieter Sell

DECHEMA e.V.

Abteilung Biotechnologie

Theodor-Heuss-Allee 25

60486 Frankfurt/Main

Germany

Roberta Sisto

University of Foggia

Department of Economics, Mathematics and Statistics (SEMS)

71100 Foggia

Italy

Christoph Syldatk

Karlsruhe Institute of Technology

Faculty of Chemical and Process Engineering

76128 Karlsruhe

Germany

Nils Tippkötter

TU Kaiserslautern

Lehrgebiet Bioverfahrenstechnik

Gottlieb-Daimler-Str. 44

67663 Kaiserslautern

Germany

Roland Ulber

TU Kaiserslautern

Lehrgebiet Bioverfahrenstechnik

Gottlieb-Daimler-Str. 44

67663 Kaiserslautern

Germany

Peter Welters

Phytowelt Green Technologies

Kölsumer Weg 33

41334 Nettetal

Germany

1

Introduction to Renewable Resources in the Chemical Industry

Roland Ulber, Kai Muffler, Nils Tippkötter, Thomas Hirth, and Dieter Sell

Processes in the chemical industry are historically based on fossil resources. During industrial revolution, energy sources like peat and such renewable biomasses as wood were substituted by coal and later on by natural gas and petroleum oil. The latter has been, until now, the main resource for raw materials and the energy supply for the private sector. Due to its very beneficial properties in terms of chemical synthesis processes, only a minor proportion of approximately 10% of this plentiful resource is used for such purposes, whereas 90% is utilized for energy and transport. With regard to the increasing population and energy demand and oil consumption of developing countries, the limited availability of crude oil, and financially motivated trading operations, the price of oil rises steadily and reached a peak of nearly 150 USD per barrel in 2008. It is assumed that most of the known so-called supergiant oil-fields cross the oil-peak, which comes along with a decrease in the discovery of novel oil springs. Therefore, alternatives have to be introduced to reduce the dependency on these transient fossil fuels. But one has to keep in mind that alternative fuels and resources for chemical building blocks have to compete against classical fossil compounds.

Currently, the prices of most bulk and specialty chemicals are too low for biotechnological routes to compete. It is estimated that competition begins at feedstock prices above $2 per kilogram. Nevertheless, the share of biotechnologically produced chemicals is expected to increase from approximately 5% to 20% in the year 2010. The greatest impact is expected in the segment of fine and specialty chemicals with up to 60% of the products based on biotechnological processes. Interfacing with green biotechnology for enhanced crop properties and increased plant breeding can be expected. More attention is paid to the lignocellulose feedstock, which is extensively discussed and examined to be used as a sustainable raw material for ethanol production. In addition, a few current trends focus on C1 carbonic compounds such as methanol and methane, fatty acids and glycerol from plant oil, and whey-based substrates that can be used as input compounds for a chemical refinery.

If one has a closer look to current activities of oil companies, it is obvious that the time is changing. Several efforts to utilize sustainable biomass feedstocks for recovering fuel substitutes were carried out by these companies. But the exploitation and utilization of the biomass feedstock have to be implemented very carefully to avoid such an already occurred competition of energy crops with food production, if first-generation biomass fuels were considered. However, the complete substitution of fossil resources by biobased fuels and raw materials within the near future is quite improbable, considering the current process operation’s dependency on large amount of biomass feedstock. Therefore, socioeconomic trends must focus on a holistic approach, where fossil as well as biological resources have to be used in a complementary way. At least at the laboratory scale, for 6 of the 10 best sellers of the chemical industry alternative biotechnological production processes are under development (ethylene, ethylene oxide, dichloroethane, propylene, formaldehyde, and propylene oxide). In Western Europe alone, the annual demand for ethylene and propylene is 40.5 million tonnes. World production of the basic building blocks of the chemical industry, including polymers, exceeds 500 million tonnes. This fact clearly shows that large quantities of renewable raw materials must be made available for the production of bulk chemicals. Despite the 5.6 million hectares of arable land currently lying fallow in the EU, this cannot be limited to the provision of sugar or starch. On the contrary, what is required is the holistic utilization of diverse renewable resources. Nature provides around 170 billion tonnes of plant biomass, of which hitherto only approximately 3–4% have been commercially exploited. The crux of the matter is how much can, and indeed may, be used of the remaining 96% in a sustainable way? And how much energy will this entail?

If one considers the biomass feedstock, the number of different categories is enormous and includes grains, sugar crops, oilseed crops, agricultural wastes, food-processing wastes (liquid and solid), wood, wood chips, bark, mill residues, forest residues, pulping liquors, manures, and algae. With regard to an increasing utilization of crops in the material and energy sector, the prices for comestible goods also increase and a couple of social problems arise. Therefore, the exploitation of forest residues or special planted wood-based biomass is – based on our current knowledge – accompanied only by insignificant social problems. Especially for European countries, prosperous predictions for utilization of such materials do exist. Owing to a declining population, the need for agricultural crop lands for food supply will decrease and could be used for industrial plantations. As a positive consequence, new collaborations between producers (farmers) and chemical manufacturers will be established in analogy to the already existing collaborations between the starch-processing companies and manufacturers.

One potential starting point is the development of the lignocellulose biorefinery. However, the sustainable development of the biorefinery depends on the extensive process integration. A concept devised solely for the production of basic and fine chemicals may well fail to achieve its target. More importantly, the materials applied should be used both for energy (in the form of heat and power) and for the production of chemicals and materials. All planning must allow for the fact that the renewable resources in question should not only be allocated to biotechnology but also in fact in the area of energy supply where there is a tendency to draw increasingly on biomass. Hütermann and Metzger, for example, state that “… global energy provision on the basis of biomass is feasible without detriment to food production. …” According to their calculations, a biobased economy would require 22.3 billion tonnes of bio-oil from pyrolysis. This corresponds to approximately 35 billion tonnes of biomass solely for conversion into energy. In the construction materials sector, too, there is a growing trend to utilize renewable resources. To quote the “Informationsknoten nachwachsende Rohstoffe” (Renewable Resources Information Centre), “… nature provides a huge range of plant and animal raw materials that are suitable for a variety of applications. The challenge for the future is to exploit this inexhaustible raw materials potential without detriment either to man or to the environment and without impairing the standard of living of the population. …”. Only the concerted efforts of all interest groups in the field of renewable resources can pave the way for a meaningful development. In the following chapters, the options for the biotechnological and chemical industries will be examined in more detail. In view of the raw materials figures initially mentioned, one of the priorities will be (ligno)cellulose as, with around 95%, it accounts for the bulk of renewable raw materials. A further priority will be the more intensive utilization of methane and methanol from both fossil and renewable sources.

Assuming an estimated annual biomass production of 170 billion tonnes by biosynthesis, of which 75% are carbohydrates mainly in the form of cellulose, chitin, starch, and sucrose, 20% lignin, and only 5% other natural products such as fats (oils), proteins, and diverse ingredients, the prime concern should be efficient access to carbohydrates and processing them into chemical mass products and finished products. This will not take place overnight since the relevant technologies first have to be developed; moreover a shift from fossil to sustainable processes can only be implemented if it is seen to be economically viable. The substitution of fossil resources by renewable resources can, therefore, only proceed in stages. To combine the markets for fossil and renewable resources would only make a prognosis of the most favorable time for the change more difficult.

Raw materials on the basis of biomass cannot simply be converted into conventional plants like naphtha crackers; hence it is postulated that new processes for the conversion of biomass first need to be developed. If used intelligently, chemical reaction technology, including catalysis and process engineering together with biotechnology, may provide economic solutions to this technological problem. The following strategies are, in principle, possible:

utilization of the chemical structures produced by nature without any chemical modification;one-step modification of these structures;multistep chemical modification;total degradation to C-1 fragments (e.g., synthesis gas or methane) and controlled synthesis to obtain the desired molecules.

The chemical industry owes its success to the principle of unit construction: from simple basic substances, like ethylene, carbon monoxide, or hydrogen, more complex precursors can be produced under controlled conditions by chemical reactions; due to the variety of combination options, the latter can in turn be converted into inconceivable quantities of derivatives and end products. Chemistry learned how to produce chemically pure basic substances from oil that are simple to handle and exactly defined; this is performed highly efficiently in refineries. This was the key to its success. Without exact knowledge of this functional principle, the triumphant success of plastics would have been just as impossible as the production of thousands of other chemical products that today make our lives safe and comfortable.

Within the following chapters, this book tries to answer some of the important questions to establish biorefineries within the existing chemical industry. What should be the impact from plant breeding for new biorefineries? Is it possible to design new and better plants which fulfill most of the requirements (high contents of fermentable raw materials, less by-products, easy to hydrolyze)? Initially the chemical industry considered fermentation of plant carbohydrates as the only viable solution. But now, with the increasing success of globally grown genetically modified plants, plant enzymes, cell cultures, and whole plants have been taken seriously for chemical production processes. Pharmaceutical proteins, SMDs, and fine chemicals have been the first choice for production. But with ever-rising prices of fossil resources, chemical commodities such as platform chemicals (e.g., succinate, itaconic acid), intermediates, or polymers are now considered as economically viable (see Chapter 2). However, is the world agro capacity big enough to deliver all raw materials needed? The primary purpose of agriculture is food production and has been so throughout human history. During the last decade, environmental and economic concerns have led to growing interest in fuel and energy crop production. Therefore, the production of renewable chemicals from agricultural raw materials will be in direct competition with both food and fuel production for space, resources, labor, and funds. Although the high value of chemical products may make them economically viable, they may have an undesirable competitive effect on food production. However, food, fuel, and chemical production are not necessarily mutually exclusive. The biorefinery concept aims to make best use of whole crop plants by producing numerous products from a single resource (discussed in Chapter 3). In comparison to their fossil counterparts, process chains based on renewable raw materials differ in many aspects. Operations for cultivation, harvesting, and provision of renewable raw materials take place in a natural environment. The raw materials accrue spatially distributed on large areas. Amount and characteristics of the resources underlie seasonal variances and restrictions. As a rule, the abilities and capabilities for storage are limited. Long-distance transports are disadvantageous because of comparable high water content and low calorific values. Thus, Chapter 4 explains the essential adjustments for the logistics of renewable raw materials. Looking at the existing value chain of industrial biotechnology, all fermentation processes which have been commercialized in the last decades for the production of one of the building blocks such as ethanol or amino acids presently rely on carbohydrates as feedstock. Moreover, the majority of fermentation processes, which recently are in the feasibility stage, also start from these feedstocks at the moment. Chapter 5 gives an overview about the existing value chains and the products already produced in the so-called type-one biorefineries, whereas future biorefineries are described in Chapter 6. The establishment of new industrial firms, such as a biorefinery, in a rural area can be seen as an opportunity to revitalize the local economy, and to revert the negative demographic trend, which very often characterizes those areas. However, apart from the scarce density of capital and human resources locally existing, the development of a biorefinery in those places strictly depends on the acceptance level of the local communities which, in assessing the socioeconomic and environmental implications, take into account a series of concerns particularly related to understand how their quality of life may change as a result of the industrial project implementation. These economic and social implications of the industrial use of renewable raw materials are discussed in Chapter 7. Potential markets for bioproducts are wide ranging, including polymers, lubricants, solvents, adhesives, herbicides, and pharmaceuticals. While bioproducts have already penetrated most of these markets to some extent, new products and technologies are emerging with the potential to further enhance performance, cost competitiveness, and market share. The market needs and opportunities for products produced by the existing and proposed new types of biorefineries are explained in Chapter 8. One major reason for the interest in biobased products is their potential contribution to the mitigation of climate change since biobased products are made from renewable resources which, during their growth, take up the same amount of CO2 as is released by biological degradation or energetic conversion in the end of the product’s life. This is a generic advantage compared to the use of fossil resources, which release the inventory of carbon accumulated and stored in the ground millions years before. However, is this true for all biobased products? Chapter 9 tries to answer this by discussing the life cycle analysis of biobased products.

The aim of this book is to highlight all areas which have to be regarded in order to realize the vision of a “biobased economy” as a sustainable industrial future based on renewable resources is often termed. The choice of the chapters is inspired by the scientific framework and the business conditions with an influence on the development of a biobased economy. How do the different authors as specialists in their fields appraise the application of renewable raw materials? Where do they see chances, where do they see need of action? “May you live in interesting times” stated Wim Soetaert in regard to the progress of biorefineries (see Soetaert, W. [2009] May you live in interesting times! Biofuels, Bioprod. Biorefin., 3, 491–492, DOI: 10.1002/bbb.173). We hope that you will have interesting time while reading this book!

2

Plants as Bioreactors: Production and Use of Plant-Derived Secondary Metabolites, Enzymes, and Pharmaceutical Proteins

Peter C. Morris, Peter Welters, and Bernward Garthoff

2.1 Introduction

The organic chemical industry is largely based on materials derived from photosynthetically active organisms: plants (coal) and algae (petrol). In addition to these fossil sources, the chemical industry in Germany obtains 10% of its raw material from renewable resources, with more than 90% of these from plants. Due to dwindling fossil reserves, the focus of research has shifted to replace petrochemically derived chemicals by renewable plant-derived material. Initially the chemical industry considered fermentation of plant carbohydrates as the only viable solution. But now, with the increasing success of globally grown genetically modified (GM) plants, plant enzymes, cell cultures, and whole plants have been taken seriously for chemical production processes. Pharmaceutical proteins, small molecule drugs (SMDs) [1], and fine chemicals have been the first choice for production. But with ever-rising prices for fossil resources, chemical commodities such as platform chemicals (e.g., succinate, itaconic acid), intermediates, or polymers [2] are now considered as economically viable.

This chapter will remind the reader that for all these new developments there are already examples of established production processes where plants, plant cell cultures, plant enzymes, or plant (secondary) metabolites play a major role. It will give examples where genetic modification of plants and the use of plant enzymes and ingredients have increased the economical and ecological potential of plants as renewable resources for a sustainable chemistry.

2.2 Renewable Resources in the Chemical Industry

The chemical industry is a raw material- and energy-intensive industry. Due to the scarcity of fossil resources, steadily increasing oil prices, and a need to reduce greenhouse gases, renewable resources from plants will be an increasingly important issue for the industry over the coming years. Germany, fourth in the world in chemical production, will take a leading role in these efforts as manifested by high investments of the German chemical industry in industrial biotechnology R&D.

Presently, around 10% of basic material for the chemical industry stems from renewable resources, mainly plant materials. The sustainability of chemical processes can be increased by the use of fermentation processes or direct biocatalytic steps. Unlike most chemical reactions, biocatalytically driven reactions are highly stereo-selective for the substrate and the resulting product due to the intrinsic properties of the enzyme activities, resulting in particularly high specificities for substrates and reactions. In addition, natural enzyme-based processes operate at lower temperatures and atmospheric pressure, and they produce less toxic waste than conventional chemical processes. As an example, the conversion of elemental nitrogen to ammonium demands high pressures and temperatures, and the use of metal catalysts in the Haber–Bosch process. In contrast, bacterial nitrogen fixation occurs at room temperature and normal pressure. Nitrogen fixation by free-living bacteria is widespread, but the rate of fixation is relatively low (15 kg/ha/year) as it is limited by the available energy. In contrast, nitrogen fixation rates from 75 to 300 kg of N/ha/year are common in various combinations of legume–rhizobia [3].

The production of aromatics in a sustainable fermentation process is a challenging future task where interdisciplinary skills and close cooperation of microbiologists and plant specialists will be necessary. The plant shikimate pathway, synthesizing anthranilate out of erythrose, serves as a prime example that is waiting to be converted into a fermentation process or a whole plant production via an interdisciplinary approach. Currently, however, it may be easier to use a waste compound from the forest industry to be converted by a simple chemical reaction into an aromatic compound (Figure 2.1).

Figure 2.1 Example of a waste product from forest industry being converted in a simple one-step chemical reaction into an aromatic compound (α-pinen into cymol;

drawing by Dr. Frank Kastenholz, Phytowelt GreenTechnologies).

2.2.1 Commodity Production

When polymers or commodity production in the chemical industry is considered, a tacit consensus is that plants cannot compete with petrochemically derived products. But at a closer look, numerous examples where the chemical industry uses plant-derived materials on a large scale become obvious. For example, plant oils are already widely used as raw materials for the synthesis of a huge number of compounds. Fatty acids are used as lubricants, emulsifiers, agrochemicals, fragrances, and pharmaceuticals. The world production of plant fatty oils currently exceeds 130 million metric tonnes per annum [4] and plant oils are one of the most important sources for sustainable chemistry. Since glycerol and fatty acids, together with their methyl esters, are the basic oleochemical compounds in industry currently generated from crude oil by various chemical and biocatalytic processes, the transformation of plant oils and fats into oleochemicals by hydrolysis of natural triglycerides into glycerol and mixed fatty acids and/or fatty acid derivatives as well as purification of the released compounds represents a major progress in sustainability [5]. Optimized plant oils are of increasing importance for sustainable chemistry. In the future, the use of data mining will be increasingly important in order to obtain novel biocatalysts (enzymes) for the processing requirements of fats and oils with iterative modules of phytomining and in silico screening, which provides a straightforward approach for identification of biocatalysts and opens new production routes in sustainable chemistry.

2.2.2 Production Problems

A major problem for the use of natural plant-derived matter in the chemical industry occurs when molecules are under-functionalized because they have only one group that can be easily modified or used for chemical linkage formation. Especially fatty acid- or isoprene-derived molecules need the introduction of one or two functionalized groups.

To address this problem, several successful attempts have been made to genetically modify plants to increase the content of specific fatty acids, either of longer chain length than the usual C16 to C18 [6–9], or with chain lengths below or equal to C10 to C12 [10, 11], or with special functional groups as in erucic acid [12]. Nearly every major seed or agro-biotechnology company (Table 2.1) has patents for the alteration of fatty acid composition, either to improve nutritional value for humans [7, 13], pigs [14], and fishes [15] or to comply better with industry standards [16]. For example, SemBioSys in Canada was able to produce safflower lines that are able to produce more than 60% of their oil content as α-linoleic acid, some lines even produced nearly 90% of their oil as α-linoleic acid [17]. An unusual example is where the production of branched or cyclic structures within a fatty acid molecule is proposed [18, 19].

Table 2.1 Patents on oilseed transformation and alteration of fatty acid profiles.

The oxidation of the omega-methylgroup is of special interest because it opens the way to linear polymers such as polyesters or polyamids [20]. Enzymes executing this type of reaction belonging to the class of cytochrome P450 enzymes have been reported for the production of omega-hydroxy fatty acids and the biosynthesis of TAG-/DAG-based estolide polyesters in petunia stigma [21]. Very rich sources of omega-oxidized fatty acids are the protective polymers found in specific tissues of all higher plants. The suberins and cutins are composed of a wide variety of oxygenated fatty acids, for example, saturated omega-hydroxy fatty acids and alpha,omega-diacids [22]. The most common monomers in cutins are 10,16- dihydroxy-C16 acid, 18-hydroxy-9,10-epoxy-C18 acid, and 9,10,18-trihydroxy-C18 acid. These monomers are produced in the epidermal cells by omega hydroxylation, in-chain hydroxylation, epoxidation catalyzed by P450-type mixed function oxidases, and epoxide hydration [23]. The composition and the enzymes involved in the process of suberins and cutins promise to be a rich source for reactions sought for industrial biotechnology to functionalize hydrophobic plant compounds.

2.2.3 Natural Rubber as Compared to Synthetic Rubber

For the chemical industry, the most useful derivative from the terpenoid family is natural rubber (NR), polyterpene. Global rubber consumption (both NR and SR) is forecasted to reach 24.3 million metric tons in 2010, with NR production of 10.2 million metric tons. In the longer term, global rubber consumption is predicted to reach 33.9 million metric tons by 2020, with NR production of 15.4 million metric tons. Global NR production is estimated to be 9.9 million tonnes at the end of 2008. Thus, nearly half of the global rubber production comes from plants. The main advantage of NR is the uniformity of the polyterpene molecule, rendering a unique uniformity to the polymer properties not achievable by chemical elastomer production [2]. Due to the superior properties of NR, a slightly higher price than for SR is acceptable by the market. Although rubber trees stem from Brazil, most NR comes from Asia. The Asian plantations that were started at the end of the 19th century were founded on a very small number of trees [24]. Therefore, the genetic variability is extremely small and it is feared that diseases, especially the pathogen Microcyclus ulei, the causative agent of South American leaf blight [25], may endanger productivity. Research for alternative rubber sources is being conducted, either to improve new varieties by breeding or genetic engineering to render them resistant to the most common diseases, or to find alternative plants such as guayule or Russian dandelion, suitable for production of equal quality and quantity of NR. The Russian dandelion Taraxacum koksaghyz is rich in secondary metabolites including NR (poly-cis-1,4-polyisoprene). Because alternative sources of rubber are becoming economically attractive, research into this subject has been rejuvenated [26] and recent progress has been made regarding the identification and manipulation of rubber biosynthesis genes and latex accessibility [27, 28]. However, further work is still needed as rubber trees render yields of up to 3000 kg/ha/year, whereas guayule yields 2000 kg/ha/year and Russian dandelion only 150–500 kg/ha/year.

2.2.4 Cellulose and Other Fibers

Each year photosynthetically produced cellulose (the most common organic compound on Earth) amounts to 1.3 billion tonnes. Cellulose is a polysaccharide consisting of a linear chain of several hundred to over ten thousand β(1→4) linked D-glucose units. About 33% of all plant matter is cellulose (the cellulose content of cotton is 90% and that of wood is 50%). For industrial use, cellulose is mainly obtained from wood pulp and cotton. It is mainly used to produce paper; cardboard and textiles.

The natural fiber industries employ worldwide millions of people, especially in developing countries and their products are processed in many small and large industries. The promotion of the use of natural fibers as a CO2 neutral resource could contribute to a reduction of climate-endangering gases, and the year 2009 has been assigned by the UN to be the international year of natural fibers. Production of man-made fiber from cellulose (cellulosics), of which rayon accounts for by far the largest portion, was 3.5 million tonnes in 2008. Cotton production has grown steadily. It is estimated to reach 25 million tons in the season 2010/2011.

Although cotton production has increased significantly over the last decades, it had not been able to keep pace with the growth of synthetic fiber production, which overtook in the mid-1990s. Nevertheless, planting of genetically engineered cotton plants has improved yield, especially in India. These significant increases of yield efficiency are already apparent when simple agricultural traits such as herbicide and insect resistance are employed (Figure 2.2). Together with genetic modifications to improve quality of the yarn [29, 30], cotton will increase its market share when these elite events hit the market [31].

Figure 2.2 (a) Increase of productivity in Indian cotton harvest, between 1982 and 1997 harvest grew from 200 kg to 300 kg/ha, since the introduction of GM-cotton in 2002 productivity nearly doubled to 550 kg/ha; (b) out of 9.4 million ha cotton cultivation in India, nearly 8 million are planted with GM cotton.

2.2.5 Paper Production

By far the major use of cellulose is in paper and cardboard production. In 2006 160 million tonnes of pulp were produced from 530 million m3 of wood. 95% of this was made from plantation wood. It is estimated by the United Nations Food and Agriculture Organization (FAO) that by 2020 all wood uses will be covered by production from plantations on an area of 450 million ha which is around 15% of the whole forested area of today (3.5 billion ha). 50 million tonnes of lignin are produced each year as a by-product of paper production, only 2% is used for lignin-derived products, 98% is burned for energy purposes. If this material could be used instead in chemical industry, one-sixth of today’s petrochemically produced chemicals could be replaced by renewable substances. Without reducing the amount of land used for food production, wood production would be able to replace all petrochemically derived material production if we learn how to use cellulose, hemicelluloses, and lignins in a proper way and to alter their properties according to the demands of clients of the chemical industry. With another 150 million ha of tree plantations, we would be able to replace all naphtha by renewable resources.

One way to achieve this is to use plant-derived enzymes to introduce functionalities into plant materials such as fatty acids- and isoprene-derived materials (e.g., omega-oxidation of fatty acids) and use (plant) enzymes to modify over-functionalized molecules like sugars or sugar-derived polymers such as cellulose, starch, and hemicellulose in a directed and controlled way. The third application for plant enzymes would be the depolymerization of lignin into its monomers (reducing complexity of plant-derived products) or using plant enzymes to be able to copy in vitro the complexity of plant molecules such as taxol, artemisin, vincristin, or campthothecin. Interesting technologies are already under development, for example the linear lignin production technology developed by CIMV in France. More of these technologies are to come and will improve the variety of biopolymers (Figure 2.3).

Figure 2.3 Number of newly developed polymers between 1900 and 2020 (prediction). Petrochemically derived building blocks had been mainly developed in the 1940s and 1950s of the 20th century. New biopolymers gained in importance in the 1990s and will be the leading innovation driver in polymer chemistry in the 21st century.

Courtesy of Dr. Manfred Kircher, CEO of CLIB2021.

In China, transgenic Bt poplar trees are already grown in large-scale field trials (300 ha). These trials are part of a reforestation program and aim to reforest an area of approximately 17 million ha by the year 2012. In addition to poplars, other forest trees such as eucalyptus, birch, spruce, and pine have been GM. In Germany, transgenic poplar trees had to be destroyed before they were able to flower and spread their pollen. Instead, Germany intends to increase economical value of poplar plants by improved methods of breeding, for example, somatic hybridization to increase biodiversity and combine properties of poplar species, which are difficult to cross (FNR, R&D project “Innovative Hybridpappeln – Schnelles Wachstum für Deutschland,” FKZ 22004105, funded by the German Ministry of Agriculture).

2.2.6 Starch Production

World production of starch in crop plants is estimated at 2.5 billion tonnes/year. The Chinese government is planning to double its starch grain production (especially rice) to 540 million tonnes by the year 2020 by genetic engineering of crop plants [32]. Starch is composed of a polymer of the sugar glucose. Despite its simple composition, starch has a complex structure, forming semicrystalline granules. The starch industry extracts starch from cereal grains and potatoes and processes it into several hundreds products, from native starches to physically or chemically modified starches, liquid, and solid sugars. Starch products are used as ingredients and functional supplements in food, nonfood, and feed applications. It also generates co-products that are sold into animal feed (e.g., wheat proteins, corn gluten feed) and food (e.g., wheat gluten). The total quantity of starch produced in Europe in 2008 was 9.4 million tonnes and the consumption of starch and starch derivatives (excluding co-products) in 2008 was 8.7 million tonnes – 39% of which were used for nonfood applications) (Table 2.2).

Table 2.2 Uses of starch in the European industry.

One of the earliest known industrial uses of starch was to “size” and stiffen textiles. It is also added to yarns to increase mechanical strength and resistance to friction wear and helps resist moisture penetration. And it can serve as a stabilizer and filler for colored inks when fabrics are overprinted. The detergent industry uses starch products for the production of biodegradable, nontoxic and skin-friendly detergents. Starch products are also used in an array of less obvious applications: as feedstock in fermentation for the production of amino acids, organic acids, and enzymes, and also by the chemical industry for the production of surfactants, polyurethanes, resins, and in biodegradable plastics. Starch is also used in the construction industry, for concrete admixtures, plasters, and insulation, as well as in oil drilling, mineral, and metal processing. The paper and board industries are the largest nonfood starch-using sector, using approximately 60% of the total industrial starch. Starch is also used quite extensively in cosmetics and health care products.

One product made directly by the fermentation of starch, cyclodextrin, is especially interesting as a fermentation product. In 1998 the global market was estimated between 1800 and 3600 tonnes. As stated by the company, Wacker Chemie had at that time a production capacity of 3000 tonnes. Today, 10 years later, they have increased their production capacity to 7500 tonnes of cyclodextrins a year. These molecules are used as stabilizers and excipients in the pharmaceutical, life science, cosmetics, food, and agricultural industries.

Potatoes are the world’s fourth largest food crop, following rice, wheat, and maize. The FAO reports that the world production of potatoes in 2009 was 330 million tonnes [33]. The world production of potato starch exceeds 2 million tonnes per annum. It is regarded as having superior properties to cereal starches and is the preferred starch for paper and pulp surface sizing, which accounts for more than 50% of the use in this particular industry. However, wheat and maize starch are usually used as they are a lower cost option. That might change now since a high amylopectin-containing GM potato got approval from the EU Commission. This potato, with the commercial name Amflora, contains almost only the amylopectin form of starch and will render the industrial use of it cheaper, as it is no longer necessary to separate amylose and amylopectin [34]. Another approach to make potato starch more valuable for industrial uses is to modify the amylose to give it new properties. To make use of starch as a fat-resistant packaging material a hydroxypropylated amylose has been developed by several industrial and academic laboratories independently (e.g., [35]). Another way to improve competitiveness is to improve pest resistance [36]. A Phytophthora resistant GM potato line [37, 38] is aimed at commercialization in 2014. A canker-resistant potato produced by somatic hybridization is under development by a consortium of potato breeders, academic institutes, and Phytowelt GreenTechnologies funded by the BMBF [39].

2.2.7 Sugar Production and Improvement of Yield by Genetic Engineering

World sugar production for the 2009/10 marketing year is estimated at 153.5 million tonnes. Brazil, India, Thailand, and China account for 50% of world sugar production and 59% of world exports [40]. Sugar is the most widely used feedstock for industrial fermentation. The first transgenic sugar beet has been approved in the United States in 2005. In 2009 it had 90% of the US market share, although the legal status of this crop is at the time of writing under dispute [41]. Sugarcane, being a monocotyledonous plant, has been difficult to improve by plant transformation. First attempts are trying to render sugarcane disease resistant, herbicide tolerant, and drought resistant [42]. A new research alliance has been established this year between BASF and KWS with the aim of improving yield by 15% by the year 2020, mainly through improvements in drought resistance.

2.3 Fine Chemicals and Drugs

The development of modern human culture was made possible due to the intensive use of plants and plant products as valuable sources for nutrition, commodities, and energy. However, only recently we have come to see plants as a cornerstone of sustainable industry by exploiting lead structures and biosynthetic pathways for the modification of plant-derived renewable resources.

It is most important to note that usage of plant enzymes and their biosynthetic abilities is not restricted to the use of whole plant systems (e.g., as bioreactors). Through the targeted use of biotechnology and biodiversity, it is possible to isolate plant genes and optimize their coding regions to produce enzymes in microorganisms with specificities and stabilities tuned to particular industrial purposes. The rapid elucidation of biosynthetic pathways made in part possible through advanced genomic tools has made natural products again the molecules of choice for drug development. Indeed, half of the drugs currently in clinical use are natural products and it is expected that the market size of biotechnology-derived small molecules will exceed US$100 billion in 2010 and US$400 billion in 2030 [43].

2.3.1 Plant Cell Culture

Plant-derived natural products have a high chemical diversity and function in a multitude of ways as flavor enhancers, agricultural chemicals, and most importantly, as human medicines. Securing the production of pharmaceutically active natural products has often been a challenge due to slow growth rates of some species, low yields found in nature, and unpredictable variability in accumulation [44]. However, especially in the case of very complex structures, chemical synthesis is economically impossible. Therefore, the optimization of plant cell culture not only by introducing and improving biosynthetic pathways by genetic engineering but also by optimizing culture conditions and purification schemes are applied to achieve a reliable production of pharmaceutical products.

2.3.2 Terpenoids

One of the best understood biosynthetic pathways for terpenoids is the biosynthesis for menthol in mint plants. All the enzymes are identified, cloned, and characterized [43]. Menthol plays an important role as aroma in food, cigarettes, and medications for the pulmonary tract and in cosmetics. Improvements of yield or quality of monoterpene production by genetic engineering were successfully tried but the market size is too small to be worth the amount of time and money expended for deregulation.

Limonene as a by-product of orange juice production can be used for polymer production together with CO2 to form a polystyrol-like foam. Menthon can be used as a precursor for branched dicarbonic acids and alpha-pinen (a by-product of the forest industry) as precursor for cymol production or for enzymatic verbenone production. Other important terpenoids are phytosterols. They are used in the production of steroid hormones such as cortison or progesteron by Bayer Schering Pharma. Probably the most important example where plant secondary metabolism and microbial fermentation are synergistically combined, steroid hormones, are produced from phytosterols. A fermentation process by Bayer Schering Pharma uses a plant metabolite and converts it by a single-step microbial fermentation into the desired end product.

2.3.3 Amino Acids

The production of amino acids such as cysteine is sometimes made from plant-based raw materials in a fermentative production process [45]. Cysteine is a sulfur-containing amino acid that is primarily used in the food industry, for example, for baked goods and flavored production, but it is also used for drugs and cosmetics. Since it is manufactured from purely plant-based and inorganic starting materials, it is also characterized as halal, kosher, and vegetarian-grade. This process has been nominated for the EU Commission’s European environmental prize competition and has received the Environmental Prize for Vegetarian Cysteine from the Federation of German Industries. But the main producer of amino acids by fermentation is Evonik Industries, who has established a sophisticated process where 14 different amino acids are currently produced in large-scale industrial production size by fermentation [46].

2.3.4 Fatty Acid Derivatives

Photosynthetically active organisms are the only ones being able to synthesize tocopherols and tocotriols. These compounds are essential to mammalian organisms as precursors to vitamin E, and protecting polyunsaturated fatty acids from peroxidation. From the recent elucidation of their biosynthetic pathway [47], it is now possible to improve the vitamin E content of plants by genetic engineering, thus improving the nutritional value for food and feed purposes. Vitamin A is one of micronutrients in the focus of World Health Organization, FAO, and other organizations to be supplied in higher amounts to malnourished people in developing countries as key factors promoting health. The relevant programs include fortification of food, breeding of crops to improve content in plants already producing vitamin A precursor, or to introduce it in parts of plants where it does not occur naturally in crop plants by genetic engineering [48]. Although carotinoid biosynthesis is regulated in a complex way, recent progress has resulted in the identification of lycopine-β-cyclase as a rate-limiting step in chromoplasts and has resulted in an increase of total carotinoid synthesis in tomatoes by 50% [49]. Enhanced vitamin A production in the endosperm of rice has been achieved already 10 years ago [50]. Commercialization in Asia, Africa, and Latin America to reduce the toll of vitamin A deficiency, mainly the blinding of 500 000 people yearly, has been fiercely fought against by anti-GM nongovernmental organizations, on the grounds of insufficient vitamin A yields. However, only 5 years later a rice variety has been presented with 23 times higher provitamin A (37 µg/g) content in the endosperm, that is, 500 g of genetically optimized rice would be sufficient to deliver the daily recommended dose of vitamin A [51].

2.3.5 Plant Protection

Pyrethroids are a very potent class of insecticide naturally occurring in chrysanthemums. The cultivation of this plant in Africa is one of the main sources of this insecticide for biological agriculture. A synthetic analog is produced by the use of plant enzymes produced microbially in Escherichia coli. DSM uses the enzyme hydroxynitrilase to produce an intermediate of pyrethroid synthesis by fermentation (Figure 2.4).

Figure 2.4 Example of a plant enzyme (Hydroxynitrilase from Hevea brasiliensis) used for the synthesis of an intermediate in the production process of an insecticide (pyrethroid) by DSM.

Drawing by Dr. Guido Jach, Phytowelt GreenTechnologies GmbH.

2.3.6 Small Molecule Drugs

Until now, microorganisms such as fungi and bacteria (often extremophiles) were used as main sources for enzymes. The growing complexity of reactions required for the production of fine chemicals, especially for the pharmaceutical industry, has increasingly drawn the attention of industrial biotechnology to plants. The high complexity of plants’ secondary metabolism, as well as the fact that most of today’s small molecule drugs (SMDs) can be traced back to a plant metabolite as the basic structure, is certainly a major reason for this development. Moreover, nature has optimized plant enzymes to work best at relatively low temperatures. Their use therefore opens new chances for energy reduction in novel industrial applications.

Besides their unmatched range of biosynthetic pathways and reaction mechanisms, plants have found during their evolution unique possibilities to produce, store, and enrich even highly toxic substances by compartmentation in specialized cell organelles or special tissues like trichomes in mint species (Figure 2.5).

Figure 2.5 Trichomes of mint plants (a) and resulting phenotype of a somatic hybridization (b, hybrid) between mint varieties (b, E33, E87: leaves of parent lines used for protoplast fusion,

unpublished results E. Baumann, Phytowelt GreenTechnologies GmbH).

As most secondary metabolites are only made in low amounts and are often found in wild-type plants not optimized for cultivation, supply of the desired molecule is often limited or at least very costly. To overcome this bottleneck, different ways have been developed to produce important metabolites or precursors in cell cultures, tissue cultures, or in higher amount in whole plants [44]. Paclitaxel (an anticancer agent) is one of these substances with high commercial value where independently established suspension cultures of genetically engineered plant cells have been patented as production process [52, 53].

The plant-derived drug artimisin (and derivatives) are used to combat malaria. Instead of using plant cell culture to get easier access to the finalized product, attempts to bring the whole biosynthetic pathway of artimisin from plants into microbes are on their way. The first trials to use plant enzymes in microbes used the enzyme amorphadiene synthase from Artemisia annua in E. coli to produce amorphadiene, a precursor of artemisin with a concentration of up to 24 µg/l culture [54]. Since then, it has been possible to produce artemisinic acid in yeast by bringing a CYP71 family P450 enzyme plant gene encoding the amorphadiene oxydase from A. annua into expression in Saccharomyces cerevisiae, yielding up to 100 mg/l culture [55] (Figure 2.6). A completely different approach has yielded plants with a higher amount of artemisinin. Made possible by the rapid falling cost of genome sequencing, a sequence-based quantitative trait loci (QTL) marker breeding approach (deep sequencing of the transcriptome) has been successfully used to raise the artemisinin concentration in A. annua up to 2% dry mass [56], more than four times of the best value so far published by Chinese sources [57].

Figure 2.6 The transfer of a cytochrome P450 enzyme (CYP71 family amorphadiene oxidase) from A. annua brought the synthesis three steps closer from amorphadiene to artemisinic acid which could then be used for chemical synthesis of artemisin ([55],

drawing from [58]).

Combinatorial biosynthesis, that is, the combination of metabolic pathways in different organisms on a genetic level allowing the use of precursors of the host cells is another promising strategy for the synthesis and industrial production of important classes of natural products, including alkaloids (vinblastine, vincristine), terpenoids (artemisinin, paclitaxel), and flavonoids [59].

Increasing the concentration of the alkaloid scopolamine in medicinal plants has been the target of much research. First results were obtained in the late 1980s when somatic hybridization was used to increase the content in Datura species, and the transformation of Atropa belladonna with the enzyme hyoscyamine-6-beta-hydroxylase lead to a shift from hyoscyamine to a nearly exclusive production of scopolamine (Figure 2.7) [60].

Figure 2.7 Enzymatic conversion of Hyoscyamine into Scopolamine by Hyoscyamine-6-beta-hydroxylase.

Drawing by Dr. F. Kastenholz, Phytowelt GreenTechnologies GmbH.

Another alkaloid whose production has been successfully improved by genetic engineering in plant cell culture and whole plants is benzylisoquinoline. This was done in poppy plants and cell cultures by RNAi inhibition of the berberine bridge enzyme, which resulted in the production of reticuline [61]. The same enzyme was also targeted in an approach to transfer the benzylisoquinoline alkaloid production from tyrosine in the Papaveraceae, Berberidaceae, Ranunculaceae, Magnoliaceae, and other plant families into microorganisms [62]. Its transfer in yeast resulted in the production of (S)-scoulerine. Magnoflorine, an antibacterial agent like palmatine and berberine, could be produced by the transfer of two other enzymes, one being a cytochrome P450 enzyme from plants. In E. coli, (S) and (R)-reticuline could be produced from dopamine [63] (Figure 2.8). (S)-reticuline has a potential as cardioprotective compound probably due to its vasorelaxant effects by inhibiting Ca2+-channels [64].

Figure 2.8 Production of alkaloids by enzymatic conversion of amino acids in plant cell, yeast, and E. coli by transfer of plant biosynthetic enzyme genes into these microorganisms,

from [63].

MAO: overexpressed mono-amine oxidase from E. coli, NCS: norcoculaurine synthase, MTs: specific O- and N-methyltransferases, BBE: berberine bridge-forming enzyme, CYP80G2: diphenyl ring bridging enzyme.

2.3.7 Polyphenols and Resveratrol

Polyphenols are reported to improve human health by a variety of mechanisms. Therefore, their reliable production in microorganisms is of special interest [65]. For example, resveratrol has been identified as an active ingredient of red wine underlying the so-called French paradox. Despite eating fat-rich food, people from Southern France suffer less from cardiac diseases than do people from Northern Europe. One of the effects appears to be the reduced clogging capacity of blood platelets in the presence of resveratrol. Although, it seems that the surplus of the European wine industry should be able to cover the demand and other plant sources such as mulberry are known, production of resveratrol in fermentation of microorganisms has been successful in yeast and E. coli by introducing two genes from plants (4CL and STS stilbene synthase [43]).

2.4 Plant-Made Pharmaceuticals

Plants lend themselves readily to the large-scale production of pharmaceutical proteins and peptides, termed plant-made pharmaceuticals, (PMP) for both human and animal applications, as this approach has the important advantages of simplicity of production, cheaper costs, and the lack of zoonitics (animal pathogens or retroviruses, prions) or bacterial endotoxins. The use of a eukaryotic host base permits the majority of mammalian-compatible post-translational protein modifications (reviewed, [66, 67]). The most prevalent recombinant pharmaceutical proteins produced in plants are vaccines and monoclonal antibodies, but enzymes, hormones, and growth factors can also be made.

2.4.1 Vaccines