Available online at www.sciencedirect.com BIOTECHNOLOGY ADVANCES ELSEVIER Biotechnology Advances 23(2005)471-499 www.elsevier.com/locate/biotechadv Research review paper Biotechnology-a sustainable alternative for chemical industry Maria Gavrilescu*,Yusuf Chistib Department of Environmental Engineering and Management.Faculty of Industrial Chemistry. Technical University lasi,7!Mangeron Blvd,700050 lasi,Romania bInstitute of Technology and Engineering.Massey University.Private Bag 11 222.Palmerston North. New Zealand Received 23 November 2004;received in revised form 23 March 2005;accepted 23 March 2005 Available online 24 May 2005 Abstract This review outlines the current and emerging applications of biotechnology,particularly in the production and processing of chemicals,for sustainable development.Biotechnology is "the application of scientific and engineering principles to the processing of materials by biological agents".Some of the defining technologies of modern biotechnology include genetic engineering: culture ofrecombinant microorganisms,cells of animals and plants;metabolic engineering;hybridoma technology:bioelectronics:nanobiotechnology;protein engineering:transgenic animals and plants; tissue and organ engineering;immunological assays;genomics and proteomics;bioseparations and bioreactor technologies.Environmental and economic benefits that biotechnology can offer in manufacturing,monitoring and waste management are highlighted.These benefits include the following:greatly reduced dependence on nonrenewable fuels and other resources;reduced potential for pollution of industrial processes and products;ability to safely destroy accumulated pollutants for remediation of the environment;improved economics of production;and sustainable production of existing and novel products. 2005 Elsevier Inc.All rights reserved. Keywords:Industrial sustainability;Biotechnology;Chemicals;Biocatalysts;Environment *Corresponding author.Tel.:+40 232 278683x2137;fax:+40 232 271311. E-mail address:mgav@ch.tuiasi.ro (M.Gavrilescu). 0734-9750/S-see front matter 2005 Elsevier Inc.All rights reserved doi:10.1016f.biotechadv.2005.03.004
Research review paper Biotechnology—a sustainable alternative for chemical industry Maria Gavrilescua,*, Yusuf Chistib a Department of Environmental Engineering and Management, Faculty of Industrial Chemistry, Technical University Iasi, 71 Mangeron Blvd, 700050 Iasi, Romania b Institute of Technology and Engineering, Massey University, Private Bag 11 222, Palmerston North, New Zealand Received 23 November 2004; received in revised form 23 March 2005; accepted 23 March 2005 Available online 24 May 2005 Abstract This review outlines the current and emerging applications of biotechnology, particularly in the production and processing of chemicals, for sustainable development. Biotechnology is bthe application of scientific and engineering principles to the processing of materials by biological agentsQ. Some of the defining technologies of modern biotechnology include genetic engineering; culture of recombinant microorganisms, cells of animals and plants; metabolic engineering; hybridoma technology; bioelectronics; nanobiotechnology; protein engineering; transgenic animals and plants; tissue and organ engineering; immunological assays; genomics and proteomics; bioseparations and bioreactor technologies. Environmental and economic benefits that biotechnology can offer in manufacturing, monitoring and waste management are highlighted. These benefits include the following: greatly reduced dependence on nonrenewable fuels and other resources; reduced potential for pollution of industrial processes and products; ability to safely destroy accumulated pollutants for remediation of the environment; improved economics of production; and sustainable production of existing and novel products. D 2005 Elsevier Inc. All rights reserved. Keywords: Industrial sustainability; Biotechnology; Chemicals; Biocatalysts; Environment 0734-9750/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.biotechadv.2005.03.004 * Corresponding author. Tel.: +40 232 278683x2137; fax: +40 232 271311. E-mail address: mgav@ch.tuiasi.ro (M. Gavrilescu). Biotechnology Advances 23 (2005) 471 – 499 www.elsevier.com/locate/biotechadv
472 M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 Contents 1. Introduction........ 472 Defining industrial sustainability..,.。。.·..·.·。····.。······· 472 3. Role of biotechnology in sustainability 473 3.l.The chemical industry.....,,...,,.,.·.·,········ 474 3.2. The applications of biotechnology in the chemical industry 475 3.2.1. Commodity chemicals,,...·+......·,....·.·,· 475 3.2.2. Specialty and life science products,··.。.··· 476 3.2.3.Agricultural chemicals................ 484 3.2.4.Fiber,pulp and paper processing,·········· 488 ” 3.2.5. Bioenergy and fuels.········· 490 3.2.6. Bioprocessing of biomass to produce industrial chemicals.·····. 491 3.2.7. Environmental biotechnology..................... 491 3.2.8.Role of transgenic plants and animals.。...·.···..···. 492 4.Concluding remarks,··,·················· 493 References. 493 1.Introduction Among the major new technologies that have appeared since the 1970s,biotechnology has perhaps attracted the most attention.Biotechnology has proved capable of generating enormous wealth and influencing every significant sector of the economy.Biotechnology has already substantially affected healthcare;production and processing of food; agriculture and forestry;environmental protection;and production of materials and chemicals.This review focuses on achievements and future prospects for biotechnology in sustainable production of goods and services,specially those that are derived at present mostly from the traditional chemical industry. 2.Defining industrial sustainability "Industrial sustainability"aims to achieve sustainable production and processing within the context of ecological and social sustainability.Sustainability and sustainable development have had different meanings in different epochs and not everyone is agreed on a common definition of these concepts.For the purpose of this review, sustainable development is understood to mean "..a process of change in which the exploitation of resources,the direction of investments,the orientation of technological development,and institutional change are all in harmony and enhance both current and future potential to meet human needs and aspirations...(It is)meeting the needs of the present without compromising the ability of future generations to meet their own needs",as defined by World Commission on Environment and Development (Brundt- land,1987).Sustainable development requires a framework for integrating environmental policies and development strategies in a global context (Hall and Roome,1996). Increasingly,sustainability considerations will shape future technological,socio-econom-
Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 2. Defining industrial sustainability . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 3. Role of biotechnology in sustainability . . . . . . . . . . . . . . . . . . . . . . . . 473 3.1. The chemical industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474 3.2. The applications of biotechnology in the chemical industry . . . . . . . . . . 475 3.2.1. Commodity chemicals . . . . . . . . . . . . . . . . . . . . . . . . . 475 3.2.2. Specialty and life science products. . . . . . . . . . . . . . . . . . . 476 3.2.3. Agricultural chemicals . . . . . . . . . . . . . . . . . . . . . . . . . 484 3.2.4. Fiber, pulp and paper processing. . . . . . . . . . . . . . . . . . . . 488 3.2.5. Bioenergy and fuels . . . . . . . . . . . . . . . . . . . . . . . . . . 490 3.2.6. Bioprocessing of biomass to produce industrial chemicals. . . . . . . 491 3.2.7. Environmental biotechnology . . . . . . . . . . . . . . . . . . . . . 491 3.2.8. Role of transgenic plants and animals . . . . . . . . . . . . . . . . . 492 4. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 1. Introduction Among the major new technologies that have appeared since the 1970s, biotechnology has perhaps attracted the most attention. Biotechnology has proved capable of generating enormous wealth and influencing every significant sector of the economy. Biotechnology has already substantially affected healthcare; production and processing of food; agriculture and forestry; environmental protection; and production of materials and chemicals. This review focuses on achievements and future prospects for biotechnology in sustainable production of goods and services, specially those that are derived at present mostly from the traditional chemical industry. 2. Defining industrial sustainability bIndustrial sustainabilityQ aims to achieve sustainable production and processing within the context of ecological and social sustainability. Sustainability and sustainable development have had different meanings in different epochs and not everyone is agreed on a common definition of these concepts. For the purpose of this review, sustainable development is understood to mean b... a process of change in which the exploitation of resources, the direction of investments, the orientation of technological development, and institutional change are all in harmony and enhance both current and future potential to meet human needs and aspirations... (It is) meeting the needs of the present without compromising the ability of future generations to meet their own needsQ, as defined by World Commission on Environment and Development (Brundtland, 1987). Sustainable development requires a framework for integrating environmental policies and development strategies in a global context (Hall and Roome, 1996). Increasingly, sustainability considerations will shape future technological, socio-econom- 472 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499
M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 473 ic,political and cultural change to define the boundaries of what is acceptable (Hall and Roome,1996). Politicians,scientists and various interest groups have periodically attempted to plan for sustainable development,to counter the earlier accepted wisdom that environmental degradation was the price for prosperity.For example,the 2002 United Nations World Summit on Sustainable Development discussed major issues such as depletion of freshwater reserves,population growth,the use of unsustainable energy sources,food security,habitat loss and global health,all in the context of social justice and environmental sustainability.Sustainable development is clearly the most difficult challenge that humanity has ever faced.Attaining sustainability requires addressing many fundamental issues at local,regional and global levels.At every level,science and technology have vital roles to play in attaining sustainability,but political decisions backed by societal support and coordinated policy approaches are just as essential.Industrial sustainability demands a global vision that holistically considers economic,social and environmental sustainability.Sustainability requires incorporating "design for environment",into production processes (Brezet et al.,2001;Wong,2001;OECD, 2001a). Compared to conventional production,sustainable processes and production systems should be more profitable because they would require less wasteful use of materials and energy,result in less emissions of greenhouse gases and other pollutants,and enable greater and more efficient use of renewable resources,to lessen dependence on nonrenewable resources (Zosel,1994;Van Berkel,2000;Gavrilescu,2004a;Gavrilescu and Nicu,2004).Sustainability demands products that not only perform well but, compared to their conventional counterparts,are more durable,less toxic,easily recyclable,and biodegradable at the end of their useful life.Such products would be derived as much as possible from renewable resources and contribute minimally to net generation of greenhouse gases. Between 1960s and 1990s,industrial production attempted to minimize its adverse impact by treating effluent and removing pollutants from an already damaged environment.Designing industrial processes and technologies that prevented pollution in the first place did not become a priority until recently (Council Directive,1996;Allen and Sinclair Rosselot,1997;World Bank,1999;EPA,2003).Newer industries such as microelectronics,telecommunications and biotechnology are already less resource intensive in comparison with the traditional heavy industry (Kristensen,1986;OECD, 1989;Rigaux,1997),but this alone does not assure sustainability.Industry is truly sustainable only when it is economically viable,environmentally compatible,and socially responsible(OECD,1998;UNEP,1999;Wong,2001).Models of sustainability have been discussed in various documents prepared by the Organization for Economic Cooperation and Development (www.oecd.org)(OECD,1989,1994,1995,1998). 3.Role of biotechnology in sustainability Biotechnology refers to an array of enabling technologies that are applicable to broadly diverse industry sectors (Paugh and Lafrance,1997;Liese et al.,2000).Biotechnology
ic, political and cultural change to define the boundaries of what is acceptable (Hall and Roome, 1996). Politicians, scientists and various interest groups have periodically attempted to plan for sustainable development, to counter the earlier accepted wisdom that environmental degradation was the price for prosperity. For example, the 2002 United Nations World Summit on Sustainable Development discussed major issues such as depletion of freshwater reserves, population growth, the use of unsustainable energy sources, food security, habitat loss and global health, all in the context of social justice and environmental sustainability. Sustainable development is clearly the most difficult challenge that humanity has ever faced. Attaining sustainability requires addressing many fundamental issues at local, regional and global levels. At every level, science and technology have vital roles to play in attaining sustainability, but political decisions backed by societal support and coordinated policy approaches are just as essential. Industrial sustainability demands a global vision that holistically considers economic, social and environmental sustainability. Sustainability requires incorporating dddesign for environmentTT, into production processes (Brezet et al., 2001; Wong, 2001; OECD, 2001a). Compared to conventional production, sustainable processes and production systems should be more profitable because they would require less wasteful use of materials and energy, result in less emissions of greenhouse gases and other pollutants, and enable greater and more efficient use of renewable resources, to lessen dependence on nonrenewable resources (Zosel, 1994; Van Berkel, 2000; Gavrilescu, 2004a; Gavrilescu and Nicu, 2004). Sustainability demands products that not only perform well but, compared to their conventional counterparts, are more durable, less toxic, easily recyclable, and biodegradable at the end of their useful life. Such products would be derived as much as possible from renewable resources and contribute minimally to net generation of greenhouse gases. Between 1960s and 1990s, industrial production attempted to minimize its adverse impact by treating effluent and removing pollutants from an already damaged environment. Designing industrial processes and technologies that prevented pollution in the first place did not become a priority until recently (Council Directive, 1996; Allen and Sinclair Rosselot, 1997; World Bank, 1999; EPA, 2003). Newer industries such as microelectronics, telecommunications and biotechnology are already less resource intensive in comparison with the traditional heavy industry (Kristensen, 1986; OECD, 1989; Rigaux, 1997), but this alone does not assure sustainability. Industry is truly sustainable only when it is economically viable, environmentally compatible, and socially responsible (OECD, 1998; UNEP, 1999; Wong, 2001). Models of sustainability have been discussed in various documents prepared by the Organization for Economic Cooperation and Development (www.oecd.org) (OECD, 1989, 1994, 1995, 1998). 3. Role of biotechnology in sustainability Biotechnology refers to an array of enabling technologies that are applicable to broadly diverse industry sectors (Paugh and Lafrance, 1997; Liese et al., 2000). Biotechnology M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499 473
474 M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 comprises three distinct fields of activity,namely genetic engineering,protein engineering and metabolic engineering.A fourth discipline,known variously as biochemical, bioprocess and biotechnology engineering,is required for commercial production of biotechnology products and delivery of its services.Of the many diverse techniques that biotechnology embraces,none apply across all industrial sectors (Roberts et al.,1999; Liese et al.,2000).Recognizing its strategic value,many countries are now formulating and implementing integrated plans for using biotechnology for industrial regeneration,job creation and social progress(Rigaux,1997). Biotechnology is versatile and has been assessed a key technology for a sustainable chemical industry (Lievonen,1999).Industries that previously never considered biological sciences as impacting their business are exploring ways of using biotechnology to their benefit.Biotechnology provides entirely novel opportunities for sustainable production of existing and new products and services.Environmental concerns help drive the use of biotechnology in industry,to not only remove pollutants from the environment but prevent pollution in the first place.Biocatalyst-based processes have major roles to play in this context.Biocatalysis operates at lower temperatures,produces less toxic waste,fewer emissions and by-products compared to conventional chemical processes.New biocatalysts with improved selectivity and enhanced performance for use in diverse manufacturing and waste degrading processes (Abramovicz,1990;Poppe and Novak, 1992;Roberts et al.,1999)are becoming available.In view of their selectivity,these biocatalysts reduce the need for purifying the product from byproducts,thus reducing energy demand and environmental impact.Unlike non-biological catalysts,biocatalysts can be self-replicating. Biological production systems are inherently attractive because they use the basic renewable resources of sunlight,water and carbon dioxide to produce a wide range of molecules using low-energy processes.These processes have been fine tuned by evolution to provide efficient,high fidelity synthesis of low toxicity products.Biotechnology can provide renewable bioenergy and is yielding new methods for monitoring the environment.Biotechnology has already been put to extensive use specially in the manufacture of biopharmaceuticals.In addition to providing novel routes to well- established products,biotechnology is being used to produce entirely new products. Interfacing biotechnology with other emerging disciplines is creating new industrial sectors such as nanobiotechnology and bioelectronics.Biotechnology has greatly impacted healthcare,medical diagnostics (Xiang and Chen,2000;D'Orazio,2003),environmental protection,agriculture,criminal investigation,and food processing.All this is a mere shadow of the future expected impact of biotechnology in industrial production and sustainability.The following sections examine the use of biotechnology in processing and production of chemicals,for enhanced sustainability. 3.1.The chemical industry The global chemical industry has contributed immensely to achieving the present quality of life,but is under increasing pressure to change current working practices in favor of greener alternatives (Ulrich et al.,2000;Matlack,2001;Carpenter et al.,2002; Poliakoff et al.,2002;Sherman,2004;Asano et al.,2004).Concerns associated with
comprises three distinct fields of activity, namely genetic engineering, protein engineering and metabolic engineering. A fourth discipline, known variously as biochemical, bioprocess and biotechnology engineering, is required for commercial production of biotechnology products and delivery of its services. Of the many diverse techniques that biotechnology embraces, none apply across all industrial sectors (Roberts et al., 1999; Liese et al., 2000). Recognizing its strategic value, many countries are now formulating and implementing integrated plans for using biotechnology for industrial regeneration, job creation and social progress (Rigaux, 1997). Biotechnology is versatile and has been assessed a key technology for a sustainable chemical industry (Lievonen, 1999). Industries that previously never considered biological sciences as impacting their business are exploring ways of using biotechnology to their benefit. Biotechnology provides entirely novel opportunities for sustainable production of existing and new products and services. Environmental concerns help drive the use of biotechnology in industry, to not only remove pollutants from the environment but prevent pollution in the first place. Biocatalyst-based processes have major roles to play in this context. Biocatalysis operates at lower temperatures, produces less toxic waste, fewer emissions and by-products compared to conventional chemical processes. New biocatalysts with improved selectivity and enhanced performance for use in diverse manufacturing and waste degrading processes (Abramovicz, 1990; Poppe and Novak, 1992; Roberts et al., 1999) are becoming available. In view of their selectivity, these biocatalysts reduce the need for purifying the product from byproducts, thus reducing energy demand and environmental impact. Unlike non-biological catalysts, biocatalysts can be self-replicating. Biological production systems are inherently attractive because they use the basic renewable resources of sunlight, water and carbon dioxide to produce a wide range of molecules using low-energy processes. These processes have been fine tuned by evolution to provide efficient, high fidelity synthesis of low toxicity products. Biotechnology can provide renewable bioenergy and is yielding new methods for monitoring the environment. Biotechnology has already been put to extensive use specially in the manufacture of biopharmaceuticals. In addition to providing novel routes to wellestablished products, biotechnology is being used to produce entirely new products. Interfacing biotechnology with other emerging disciplines is creating new industrial sectors such as nanobiotechnology and bioelectronics. Biotechnology has greatly impacted healthcare, medical diagnostics (Xiang and Chen, 2000; D’Orazio, 2003), environmental protection, agriculture, criminal investigation, and food processing. All this is a mere shadow of the future expected impact of biotechnology in industrial production and sustainability. The following sections examine the use of biotechnology in processing and production of chemicals, for enhanced sustainability. 3.1. The chemical industry The global chemical industry has contributed immensely to achieving the present quality of life, but is under increasing pressure to change current working practices in favor of greener alternatives (Ulrich et al., 2000; Matlack, 2001; Carpenter et al., 2002; Poliakoff et al., 2002; Sherman, 2004; Asano et al., 2004). Concerns associated with 474 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499
M.Gavrilescu.Y.Chisti Biotechnology Advances 23 (2005)471-499 475 chemical industry include its excessive reliance on nonrenewable energy and resources; environmentally damaging production processes that can be unsafe and produce toxic products and waste;products that are not readily recyclable and degradable after their useful life;and excessive regional concentration of production so that social benefits of production are less widely available. Chemical industry is large.The world's chemicals production in 2002 was in excess of 1.3 trillion.This industry consists of four major subsectors:basic chemicals,specialty chemicals,consumer care products,and life science products.Biotechnology impacts all these sectors,but to different degrees.Demarcation between sectors is not clearcut. General characteristics of these sectors are outlined in the following sections (OECD, 2001b). Basic chemicals or commodity chemicals represent a mature market.Most of the top 50 products by volume of production in this category in 1977 were still among the top 50 in 1993.During this period,the relative ranking by production volume of the products in this category remained largely unchanged(Wittcoff and Reuben,1996).The basic chemical industry is characterized by large plants that operate using continuous processes,high energy input,and low profit margins.The industry is highly cyclical because of fluctuations in capacity utilization and feedstock prices.The products of the industry are generally used in processing applications (e.g.pulp and paper,oil refining,metals recovery)and as raw materials for producing other basic chemicals,specialty chemicals, and consumer products,including manufactured goods(textiles,automobiles,etc.)(Swift, 1999). Specialty chemicals are derived from basic chemicals but are more technologically advanced and used in lesser volumes than the basic chemicals.Examples of specialty chemicals include adhesives and sealants,catalysts,coatings,and plastic additives. Specialty chemicals command higher profit margins and have less cyclic demand than basic chemicals.Specialty chemicals have a higher value-added component because they are not easily duplicated by other producers or are protected from competition by patents. Consumer care products include soaps,detergents,bleaches,laundry aids,hair care products,skin care products,fragrances,etc.,and are one of the oldest segments of the chemicals business.These formulated products are generally based on simple chemistry but feature a high degree of differentiation along brand lines.Increasingly,products in this category are high-tech in nature and developing them demands expensive research. Life science products.These include pharmaceuticals,products for crop protection and products of modern biotechnology.Batch production methods are generally used in making these products.The sector is one of the most research intensive and relies on advanced technology. 3.2.The applications of biotechnology in the chemical industry 3.2.1.Commodity chemicals At the basic level,life processes are chemical processes and understanding their chemistry provides a basis for devising manufacturing operations that approach nature's elegance and efficiency.Biotechnology uses the power of life to enable effective,rapid, safe and environmentally acceptable production of goods and services
chemical industry include its excessive reliance on nonrenewable energy and resources; environmentally damaging production processes that can be unsafe and produce toxic products and waste; products that are not readily recyclable and degradable after their useful life; and excessive regional concentration of production so that social benefits of production are less widely available. Chemical industry is large. The world’s chemicals production in 2002 was in excess of 1.3 trillion. This industry consists of four major subsectors: basic chemicals, specialty chemicals, consumer care products, and life science products. Biotechnology impacts all these sectors, but to different degrees. Demarcation between sectors is not clearcut. General characteristics of these sectors are outlined in the following sections (OECD, 2001b). Basic chemicals or commodity chemicals represent a mature market. Most of the top 50 products by volume of production in this category in 1977 were still among the top 50 in 1993. During this period, the relative ranking by production volume of the products in this category remained largely unchanged (Wittcoff and Reuben, 1996). The basic chemical industry is characterized by large plants that operate using continuous processes, high energy input, and low profit margins. The industry is highly cyclical because of fluctuations in capacity utilization and feedstock prices. The products of the industry are generally used in processing applications (e.g. pulp and paper, oil refining, metals recovery) and as raw materials for producing other basic chemicals, specialty chemicals, and consumer products, including manufactured goods (textiles, automobiles, etc.) (Swift, 1999). Specialty chemicals are derived from basic chemicals but are more technologically advanced and used in lesser volumes than the basic chemicals. Examples of specialty chemicals include adhesives and sealants, catalysts, coatings, and plastic additives. Specialty chemicals command higher profit margins and have less cyclic demand than basic chemicals. Specialty chemicals have a higher value-added component because they are not easily duplicated by other producers or are protected from competition by patents. Consumer care products include soaps, detergents, bleaches, laundry aids, hair care products, skin care products, fragrances, etc., and are one of the oldest segments of the chemicals business. These formulated products are generally based on simple chemistry but feature a high degree of differentiation along brand lines. Increasingly, products in this category are high-tech in nature and developing them demands expensive research. Life science products. These include pharmaceuticals, products for crop protection and products of modern biotechnology. Batch production methods are generally used in making these products. The sector is one of the most research intensive and relies on advanced technology. 3.2. The applications of biotechnology in the chemical industry 3.2.1. Commodity chemicals At the basic level, life processes are chemical processes and understanding their chemistry provides a basis for devising manufacturing operations that approach nature’s elegance and efficiency. Biotechnology uses the power of life to enable effective, rapid, safe and environmentally acceptable production of goods and services. M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499 475
476 M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 The chemical industry has used traditional biotechnological processes (e.g.microbial production of enzymes,antibiotics,amino acids,ethanol,vitamins;enzyme catalysis)for many years (Moo-Young,1984;Poppe and Novak,1992:Rehm et al.,1993:Chisti,1999: Flickinger and Drew,1999;Herfried,2000;Demain,2000;Spier,2000;Schmid,2003).In addition,traditional biotechnology is widely used in producing fermented foods and treating waste (Nout,1992;Moo-Young and Chisti,1994;Jordening and Winter,2004). Advances in genetic engineering and other biotechnologies have greatly expanded the application potential of biotechnology and overcome many of the limitations of biocatalysts of the preGMO era (Ranganathan,1976;Liese et al.,2000;Schugerl and Bellgardt,2000).Chemical companies such as Monsanto and DuPont that were once associated exclusively with traditional petrochemical based production methods have either moved exclusively to biotechnology-based production,or are deriving significant proportions of their income through biotechnology (Scheper,1999;Bommarius,2004). Important commodity chemicals such as ethanol and cellulose esters are already sourced from renewable agricultural feedstocks in the United States.New processes and renewable resources for other commodity chemicals that are currently derived almost exclusively from petrochemical feedstocks are in advanced stages of development.Examples of these chemicals include succinic acid and ethylene glycol. By the early 1990s biotechnology used for cleaner production was already contributing about 60%of total biotechnology-related sales value for fine chemicals and between 5% and 11%for pharmaceuticals (OECD,1989).Some fine chemicals being manufactured in multi-tonnage quantities using biotechnology are listed in Table 1 (Bruggink,1996; Eriksson,1997).Nearly all these products have been around for a long time,but many are now made using engineered biocatalysts. Two major areas of biotechnology that are driving transformation of the conventional chemical industry are biocatalysis and metabolic engineering(Poppe and Novak,1992; Kim et al.,2000).Genetic engineering and molecular biology techniques have been used to obtain many modified enzymes with enhanced properties compared to their natural counterparts.Metabolic engineering,or molecular level manipulation of metabolic pathways in whole or part,is providing microorganisms and transgenic crops and animals with new and enhanced capabilities for producing chemicals. A future bioethanol based chemical industry,for example,will rely on biotechnology in all of the following ways:(1)generation of high yield transgenic com varieties having starch that is readily accessible for enzymatic hydrolysis to glucose;(2)production of engineered enzymes for greatly improved bioconversion of starch to sugars;(3)genetically enhanced ethanol tolerant microorganisms that can rapidly ferment sugars to ethanol:(4) ability to recover ethanol using high-efficiency low-expense bioprocessing. 3.2.2.Specialty and life science products Biotechnology's role in production of commodity chemicals is significant,but not as visible as its role in production of agrochemicals and fine chemicals(Hsu,2004).Many renewable bioresources remain to be used effectively because they have been barely studied.Flora and fauna of many of the world's ecosystems have been barely investigated for existence of novel compounds of potential value.For example,microalgae contribute substantially to primary photosynthetic productivity on Earth,but are barely used
The chemical industry has used traditional biotechnological processes (e.g. microbial production of enzymes, antibiotics, amino acids, ethanol, vitamins; enzyme catalysis) for many years (Moo-Young, 1984; Poppe and Novak, 1992; Rehm et al., 1993; Chisti, 1999; Flickinger and Drew, 1999; Herfried, 2000; Demain, 2000; Spier, 2000; Schmid, 2003). In addition, traditional biotechnology is widely used in producing fermented foods and treating waste (Nout, 1992; Moo-Young and Chisti, 1994; Jo¨ rdening and Winter, 2004). Advances in genetic engineering and other biotechnologies have greatly expanded the application potential of biotechnology and overcome many of the limitations of biocatalysts of the preGMO era (Ranganathan, 1976; Liese et al., 2000; Schu¨ gerl and Bellqardt, 2000). Chemical companies such as Monsanto and DuPont that were once associated exclusively with traditional petrochemical based production methods have either moved exclusively to biotechnology-based production, or are deriving significant proportions of their income through biotechnology (Scheper, 1999; Bommarius, 2004). Important commodity chemicals such as ethanol and cellulose esters are already sourced from renewable agricultural feedstocks in the United States. New processes and renewable resources for other commodity chemicals that are currently derived almost exclusively from petrochemical feedstocks are in advanced stages of development. Examples of these chemicals include succinic acid and ethylene glycol. By the early 1990s biotechnology used for cleaner production was already contributing about 60% of total biotechnology-related sales value for fine chemicals and between 5% and 11% for pharmaceuticals (OECD, 1989). Some fine chemicals being manufactured in multi-tonnage quantities using biotechnology are listed in Table 1 (Bruggink, 1996; Eriksson, 1997). Nearly all these products have been around for a long time, but many are now made using engineered biocatalysts. Two major areas of biotechnology that are driving transformation of the conventional chemical industry are biocatalysis and metabolic engineering (Poppe and Novak, 1992; Kim et al., 2000). Genetic engineering and molecular biology techniques have been used to obtain many modified enzymes with enhanced properties compared to their natural counterparts. Metabolic engineering, or molecular level manipulation of metabolic pathways in whole or part, is providing microorganisms and transgenic crops and animals with new and enhanced capabilities for producing chemicals. A future bioethanol based chemical industry, for example, will rely on biotechnology in all of the following ways: (1) generation of high yield transgenic corn varieties having starch that is readily accessible for enzymatic hydrolysis to glucose; (2) production of engineered enzymes for greatly improved bioconversion of starch to sugars; (3) genetically enhanced ethanol tolerant microorganisms that can rapidly ferment sugars to ethanol; (4) ability to recover ethanol using high-efficiency low-expense bioprocessing. 3.2.2. Specialty and life science products Biotechnology’s role in production of commodity chemicals is significant, but not as visible as its role in production of agrochemicals and fine chemicals (Hsu, 2004). Many renewable bioresources remain to be used effectively because they have been barely studied. Flora and fauna of many of the world’s ecosystems have been barely investigated for existence of novel compounds of potential value. For example, microalgae contribute substantially to primary photosynthetic productivity on Earth, but are barely used 476 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499
M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 477 Table 1 Some well-established biotechnology products (by production volume) Product Annual production (tons) Bioethanol 26,000.000 L-Glutamic acid (MSG) 1.000.000 Citric acid 1.000.000 L-Lysine 350.000 Lactic acid 250.000 Food-processing enzymes 100.000 Vitamin C 80,000 Gluconic acid 50.000 Antibiotics 35.000 Feed enzymes 20.000 Xanthan 30.000 L-Threonine 10.000 L-Hydroxyphenylalanine 10,000 6-Aminopoenicillanic acid 7000 Nicotinamide 3000 D-p-hydroxyphenylglycine 3000 Vitamin F 1000 7-Aminocephalosporinic acid 1000 Aspartame 600 L-Methionine 200 Dextran 200 Vitamin B12 12 Provitamin D2 5 commercially.Microalgae are a source or potential source of high-value products such as polyunsaturated fatty acids,natural colorants,biopolymers,and therapeutics(Borowitzka, 1999;Cohen,1999;Belarbi et al.,2000;Lorenz and Cysewski,2000;Banerjee et al., 2002;Miron et al.,2002;Lebeau and Robert,2003a,b;Lopez et al.,2004;Leon-Banares et al.,2004).Microalgae are used to some extent in biotreatment of wastewaters,as aquaculture feeds,biofertilizers and soil inoculants.Potentially,they can be used for removing excess carbon dioxide from the environment (Godia et al.,2002).Other microalgae are regarded as potential sources of renewable fuels because of their ability to produce large amounts of hydrocarbons and generate hydrogen from water (Nandi and Sengupta,1998;Banerjee et al.,2002).Depending on the strain and growth conditions,up to 75%of algal dry mass can be hydrocarbons.The chemical nature of hydrocarbons varies with the producer strain and these compounds can be used as chemical precursors (Dennis and Kolattukudy,1991;Banerjee et al.,2002).Some microalgae can be grown heterotrophically on organic substrates without light to produce various products(Wen and Chen.2003). As with microalgae,sponges(Belarbi et al.,2003;Thakur and Muiller,2004)and other marine organisms are known to produce potentially useful chemicals,but have not been used effectively for various reasons.Natural sponge populations are insufficient or inaccessible for producing commercial quantities of metabolites of interest.Production techniques include aquaculture in the sea,the controlled environments of aquariums,and culture of sponge cells and primmorphs.Cultivation in the sea and aquariums are currently
commercially. Microalgae are a source or potential source of high-value products such as polyunsaturated fatty acids, natural colorants, biopolymers, and therapeutics (Borowitzka, 1999; Cohen, 1999; Belarbi et al., 2000; Lorenz and Cysewski, 2000; Banerjee et al., 2002; Miro´ n et al., 2002; Lebeau and Robert, 2003a, b; Lopez et al., 2004; Leo´ n-Ban˜ares et al., 2004). Microalgae are used to some extent in biotreatment of wastewaters, as aquaculture feeds, biofertilizers and soil inoculants. Potentially, they can be used for removing excess carbon dioxide from the environment (Go`dia et al., 2002). Other microalgae are regarded as potential sources of renewable fuels because of their ability to produce large amounts of hydrocarbons and generate hydrogen from water (Nandi and Sengupta, 1998; Banerjee et al., 2002). Depending on the strain and growth conditions, up to 75% of algal dry mass can be hydrocarbons. The chemical nature of hydrocarbons varies with the producer strain and these compounds can be used as chemical precursors (Dennis and Kolattukudy, 1991; Banerjee et al., 2002). Some microalgae can be grown heterotrophically on organic substrates without light to produce various products (Wen and Chen, 2003). As with microalgae, sponges (Belarbi et al., 2003; Thakur and Mu¨ller, 2004) and other marine organisms are known to produce potentially useful chemicals, but have not been used effectively for various reasons. Natural sponge populations are insufficient or inaccessible for producing commercial quantities of metabolites of interest. Production techniques include aquaculture in the sea, the controlled environments of aquariums, and culture of sponge cells and primmorphs. Cultivation in the sea and aquariums are currently Table 1 Some well-established biotechnology products (by production volume) Product Annual production (tons) Bioethanol 26,000,000 l-Glutamic acid (MSG) 1,000,000 Citric acid 1,000,000 l-Lysine 350,000 Lactic acid 250,000 Food-processing enzymes 100,000 Vitamin C 80,000 Gluconic acid 50,000 Antibiotics 35,000 Feed enzymes 20,000 Xanthan 30,000 l-Threonine 10,000 l-Hydroxyphenylalanine 10,000 6-Aminopoenicillanic acid 7000 Nicotinamide 3000 d-p-hydroxyphenylglycine 3000 Vitamin F 1000 7-Aminocephalosporinic acid 1000 Aspartame 600 l-Methionine 200 Dextran 200 Vitamin B12 12 Provitamin D2 5 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499 477
478 M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 the only practicable and relatively inexpensive methods of producing significant quantities of sponge biomass (Belarbi et al.,2003). Extremophiles,or organisms that have adapted to extreme conditions such as high pressure,heat,and total darkness,are attracting much interest as possible sources of unusual specialty compounds(Eichler,2001).Some extremophiles have already provided commercial biotechnology products (Henkel,1998). 3.2.2.1.Fermentation processes.Microbial fermentation is the only method for commercial production of certain products that are made in substantial quantities (Weiss and Edwards,1980;Strohl,1997;Leeper,2000;Liese et al.,2000;Schreiber,2000).Table 1 compiles the production figures for a number of established fermentation products.The antibiotics market alone exceeds USS30 billion and includes about 160 antibiotics and derivatives.Other important pharmaceutical products produced by microorganisms are cholesterol lowering agents or statins,enzyme inhibitors,immunosuppressants and antitumor compounds (Demain,2000).The world market for statins is about USS15 billion.The total pharmaceutical market is well in excess of USS400 billion and continues to grow faster than the average economy.Biotechnology processes are involved in making many of these drugs. Novel fermentation production methods for established drugs and drug precursors are being developed continually (Moody,1987;Chisti,1989,1998;Gavrilescu and Roman, 1993,1995,1996,1998;Roman and Gavrilescu,1994;Sanchez and Demain,2002).One example is the production of cholesterol lowering drug lovastatin that is also used for producing other semisynthetic statins (Chang et al.,2002;Casas Lopez et al,2003, 2004a,b,2005;Vilches Ferron et al.,2005).Various novel bioprocess intensification strategies are being put to use to substantially enhance productivities and efficiencies of numerous bioprocesses (Chisti and Moo-Young,1996). Vitamins are still mainly produced using organic chemistry,but biotechnology is making increasing contribution to vitamin production.For example,DSM Nutritional Products replaced the company's traditional;six-step process for producing vitamin B2 (riboflavin)with a one-step fermentation process that has a lower environmental impact compared with conventional production.The bacterium Bacillus subtilis is the producer microorganism.Production by fermentation was made feasible by gene engineering the bacterium to increase vitamin yield by 300,000-fold compared to what could be achieved with the wildtype strain.The one-step fermentation process reduced cost of production by 50%relative to the conventional process. Biopharmaceuticals,mostly recombinant proteins,vaccines and monoclonals, represent an entirely different class of drugs compared to small molecule compounds such as antibiotics.Examples of this class of products include tissue plasminogen activator (tPA),insulin and recombinant hepatitis B vaccine.The global market for biopharmaceuticals already exceeds USS40 billion,having grown by more than 3-fold compared to only 4 years ago (Melmer,2005).Market size of selected biopharmaceu- ticals is shown in Table 2.The total market for recombinant proteins is of course much larger when nonbiopharmaceutical products are included.A generics industry is expected to emerge around some of the older biopharmaceuticals that are now coming off patent (Melmer,2005)
the only practicable and relatively inexpensive methods of producing significant quantities of sponge biomass (Belarbi et al., 2003). Extremophiles, or organisms that have adapted to extreme conditions such as high pressure, heat, and total darkness, are attracting much interest as possible sources of unusual specialty compounds (Eichler, 2001). Some extremophiles have already provided commercial biotechnology products (Henkel, 1998). 3.2.2.1. Fermentation processes. Microbial fermentation is the only method for commercial production of certain products that are made in substantial quantities (Weiss and Edwards, 1980; Strohl, 1997; Leeper, 2000; Liese et al., 2000; Schreiber, 2000). Table 1 compiles the production figures for a number of established fermentation products. The antibiotics market alone exceeds US$30 billion and includes about 160 antibiotics and derivatives. Other important pharmaceutical products produced by microorganisms are cholesterol lowering agents or statins, enzyme inhibitors, immunosuppressants and antitumor compounds (Demain, 2000). The world market for statins is about US$15 billion. The total pharmaceutical market is well in excess of US$400 billion and continues to grow faster than the average economy. Biotechnology processes are involved in making many of these drugs. Novel fermentation production methods for established drugs and drug precursors are being developed continually (Moody, 1987; Chisti, 1989, 1998; Gavrilescu and Roman, 1993, 1995, 1996, 1998; Roman and Gavrilescu, 1994; Sanchez and Demain, 2002). One example is the production of cholesterol lowering drug lovastatin that is also used for producing other semisynthetic statins (Chang et al., 2002; Casas Lo´ pez et al., 2003, 2004a,b, 2005; Vilches Ferro´ n et al., 2005). Various novel bioprocess intensification strategies are being put to use to substantially enhance productivities and efficiencies of numerous bioprocesses (Chisti and Moo-Young, 1996). Vitamins are still mainly produced using organic chemistry, but biotechnology is making increasing contribution to vitamin production. For example, DSM Nutritional Products replaced the company’s traditional; six-step process for producing vitamin B2 (riboflavin) with a one-step fermentation process that has a lower environmental impact compared with conventional production. The bacterium Bacillus subtilis is the producer microorganism. Production by fermentation was made feasible by gene engineering the bacterium to increase vitamin yield by 300,000-fold compared to what could be achieved with the wildtype strain. The one-step fermentation process reduced cost of production by 50% relative to the conventional process. Biopharmaceuticals, mostly recombinant proteins, vaccines and monoclonals, represent an entirely different class of drugs compared to small molecule compounds such as antibiotics. Examples of this class of products include tissue plasminogen activator (tPA), insulin and recombinant hepatitis B vaccine. The global market for biopharmaceuticals already exceeds US$40 billion, having grown by more than 3-fold compared to only 4 years ago (Melmer, 2005). Market size of selected biopharmaceuticals is shown in Table 2. The total market for recombinant proteins is of course much larger when nonbiopharmaceutical products are included. A generics industry is expected to emerge around some of the older biopharmaceuticals that are now coming off patent (Melmer, 2005). 478 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499
M.Gavrilescu,Y.Chisti Biotechnology Advances 23 (2005)471-499 479 Table 2 Market size (2001)of selected biopharmaceuticals (Melmer.2005) Product Indication Market (USS million) Erythropoietin Anemia 6803 Insulin Diabetes 4017 Blood clotting factors Hemophilia 2585 Colony stimulating factor Neutropenia 2181 Interferon beta Multiple sclerosis,hepatitis 2087 Interferon alpha Cancer,hepatitis 1832 Monoclonal antibody Cancer 1751 Growth hormone Growth disorders 1706 Monoclonal antibody Various 1152 Plasminogen activator Thrombotic disorders 642 Interleukin Cancer,immunology 184 Growth factor Wound healing 115 Therapeutic vaccines Various 50 Other proteins Various 2006 Better processes for producing biopharmaceuticals such as alpha-1-antitrypsin are being developed continually (Tamer and Chisti,2001).As with numerous enzymes,many naturally occurring first-generation protein therapeutics such as insulin and tissue plasminogen activator that are being produced by modern biotechnology processes are being protein engineered to products that are potentially superior to their natural counterparts(Rouf et al.,1996).For example,various modifications of streptokinase have been used for extending its half-life in circulation,improving plasminogen activation,and reducing or eliminating immunogenicity (Galler,2000;Banerjee et al.,2004).Protein engineering has been broadly successful in altering bioactivity,stability,ease of recovery and other attributes of proteins (Nosoh and Sekiguchi,1990;Sassenfeld,1990;El Hawrani et al.,1994;Nygren et al.,1994). 3.2.2.2.Enzymatic processes.Enzymes are increasingly penetrating the chemical industry as catalysts for numerous reactions.The global market of enzymes is estimated at around USS1.5 billion and is expected to grow by 5-10%annually (Lievonen,1999). Table 3 lists major types of industrial enzymes,their substrates and reactions they catalyze. Millions of years of evolution has provided enzymes with unparalleled capabilities of facilitating life reactions in ways that are sustainable.Compared with conventional chemical catalysts,enzyme catalysis is highly specific (Scheper,1999;Bommarius,2004) and it functions under temperatures,pressures and pHs that are compatible with life (Abramovicz,1990;Roberts et al.,1999).Unlike many processes of conventional synthetic chemistry,enzymes require nontoxic and noncorrosive conditions. About 75%of the enzyme use by value is accounted for by the detergent,food and starch processing industries.These are mostly hydrolytic enzymes such as proteases, amylases,lipases and cellulases.Specialty enzymes account for around 10%of the enzyme market and are finding increasing uses in the development of new drugs,medical diagnostics and numerous other analytical uses.Of the enzymes used commercially,about 60%are products of moder biotechnology.In addition to their ever increasing diagnostics
Better processes for producing biopharmaceuticals such as alpha-1-antitrypsin are being developed continually (Tamer and Chisti, 2001). As with numerous enzymes, many naturally occurring first-generation protein therapeutics such as insulin and tissue plasminogen activator that are being produced by modern biotechnology processes are being protein engineered to products that are potentially superior to their natural counterparts (Rouf et al., 1996). For example, various modifications of streptokinase have been used for extending its half-life in circulation, improving plasminogen activation, and reducing or eliminating immunogenicity (Galler, 2000; Banerjee et al., 2004). Protein engineering has been broadly successful in altering bioactivity, stability, ease of recovery and other attributes of proteins (Nosoh and Sekiguchi, 1990; Sassenfeld, 1990; El Hawrani et al., 1994; Nygren et al., 1994). 3.2.2.2. Enzymatic processes. Enzymes are increasingly penetrating the chemical industry as catalysts for numerous reactions. The global market of enzymes is estimated at around US$1.5 billion and is expected to grow by 5–10% annually (Lievonen, 1999). Table 3 lists major types of industrial enzymes, their substrates and reactions they catalyze. Millions of years of evolution has provided enzymes with unparalleled capabilities of facilitating life reactions in ways that are sustainable. Compared with conventional chemical catalysts, enzyme catalysis is highly specific (Scheper, 1999; Bommarius, 2004) and it functions under temperatures, pressures and pHs that are compatible with life (Abramovicz, 1990; Roberts et al., 1999). Unlike many processes of conventional synthetic chemistry, enzymes require nontoxic and noncorrosive conditions. About 75% of the enzyme use by value is accounted for by the detergent, food and starch processing industries. These are mostly hydrolytic enzymes such as proteases, amylases, lipases and cellulases. Specialty enzymes account for around 10% of the enzyme market and are finding increasing uses in the development of new drugs, medical diagnostics and numerous other analytical uses. Of the enzymes used commercially, about 60% are products of modern biotechnology. In addition to their ever increasing diagnostics Table 2 Market size (2001) of selected biopharmaceuticals (Melmer, 2005) Product Indication Market (US$ million) Erythropoietin Anemia 6803 Insulin Diabetes 4017 Blood clotting factors Hemophilia 2585 Colony stimulating factor Neutropenia 2181 Interferon beta Multiple sclerosis, hepatitis 2087 Interferon alpha Cancer, hepatitis 1832 Monoclonal antibody Cancer 1751 Growth hormone Growth disorders 1706 Monoclonal antibody Various 1152 Plasminogen activator Thrombotic disorders 642 Interleukin Cancer, immunology 184 Growth factor Wound healing 115 Therapeutic vaccines Various 50 Other proteins Various 2006 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499 479
480 M.Gavrilescu,Y.Chisti/Biotechnology Advances 23 (2005)471-499 Table 3 Some industrial enzymes and their applications Enzyme Substrate Reaction catalyzed Application industry Proteases Proteins Proteolysis Detergents,food, pharmaceutical, chemical synthesis Carbohydrases Carbohydrates Hydrolysis of carbohydrates Food,feed,pulp and to sugars paper,sugar,textiles, detergents Lipases Fats and oils Hydrolysis of fats to fatty Food,effluent treatment. acids and glycerol detergents,fine chemicals Pectinases Pectins Clarification of fruit juices Food,beverage Cellulases Cellulose Hydrolysis of cellulose Pulp,textile,feed, detergents Amylases Polysaccharides Hydrolysis of starch into Food sugars and analytical applications,new uses are being developed for enzymes in production, degradation and biotransformation of chemicals,foods and feeds,agricultural produce and textiles.A few examples for bulk enzymes are the following: A new class of sugars known as isomalto-oligosaccharides is being produced using glucosyl transferases.Isomalto-oligosaccharides have potential commercial applica- tions in food industry as non-digestible carbohydrate bulking agent.They are also known to suppress tooth decay associated with consumption of conventional carbohydrates and prevent baked goods going stale. Cellulases are complexes of enzymes that synergistically break down cellulose. Cellulases are a subject of intense research because of their potential for providing fuels,food and other chemicals from widely available cellulose.Cellulases produced by Trichoderma fungi are used for 'stonewashing'jeans.Changing the relative proportions of the enzymes in the cellulase complex creates different effects on the textile fibers. Enzymes such as amylases and proteases are being added to animal feed to improve digestibility by supplementing the animals'own enzymes.A lot of the plant-derived animal feed contains antinutritional factors that interfere with digestion or absorption of nutrients.Adding enzymes such as beta-glucanases and arabinoxylanase to feed cereals breaks down non-starch polysaccharide antinutritional factors,aiding digestion and absorption of nutrients.Phytic acid found in plant matter is another antinutritional compound that reduces dietary absorption of essential minerals such as iron and zinc. Phytic acid eventually appears in animal manure as highly polluting phosphorous. Digestion of phytic acid is facilitated by adding phytases to feed.Phytase for feed supplementation became available in sufficient amounts only after it was produced in recombinant microorganisms. Extremophilic enzymes,or extremozymes,are finding increasing industrial use because of their ability to withstand extremes of temperatures and other conditions(Eichler,2001). Enzyme catalysis in nonaqueous media has created new possibilities for producing useful
and analytical applications, new uses are being developed for enzymes in production, degradation and biotransformation of chemicals, foods and feeds, agricultural produce and textiles. A few examples for bulk enzymes are the following: ! A new class of sugars known as isomalto-oligosaccharides is being produced using glucosyl transferases. Isomalto-oligosaccharides have potential commercial applications in food industry as non-digestible carbohydrate bulking agent. They are also known to suppress tooth decay associated with consumption of conventional carbohydrates and prevent baked goods going stale. ! Cellulases are complexes of enzymes that synergistically break down cellulose. Cellulases are a subject of intense research because of their potential for providing fuels, food and other chemicals from widely available cellulose. Cellulases produced by Trichoderma fungi are used for dstonewashingT jeans. Changing the relative proportions of the enzymes in the cellulase complex creates different effects on the textile fibers. ! Enzymes such as amylases and proteases are being added to animal feed to improve digestibility by supplementing the animals’ own enzymes. A lot of the plant-derived animal feed contains antinutritional factors that interfere with digestion or absorption of nutrients. Adding enzymes such as beta-glucanases and arabinoxylanase to feed cereals breaks down non-starch polysaccharide antinutritional factors, aiding digestion and absorption of nutrients. Phytic acid found in plant matter is another antinutritional compound that reduces dietary absorption of essential minerals such as iron and zinc. Phytic acid eventually appears in animal manure as highly polluting phosphorous. Digestion of phytic acid is facilitated by adding phytases to feed. Phytase for feed supplementation became available in sufficient amounts only after it was produced in recombinant microorganisms. Extremophilic enzymes, or extremozymes, are finding increasing industrial use because of their ability to withstand extremes of temperatures and other conditions (Eichler, 2001). Enzyme catalysis in nonaqueous media has created new possibilities for producing useful Table 3 Some industrial enzymes and their applications Enzyme Substrate Reaction catalyzed Application industry Proteases Proteins Proteolysis Detergents, food, pharmaceutical, chemical synthesis Carbohydrases Carbohydrates Hydrolysis of carbohydrates to sugars Food, feed, pulp and paper, sugar, textiles, detergents Lipases Fats and oils Hydrolysis of fats to fatty acids and glycerol Food, effluent treatment, detergents, fine chemicals Pectinases Pectins Clarification of fruit juices Food, beverage Cellulases Cellulose Hydrolysis of cellulose Pulp, textile, feed, detergents Amylases Polysaccharides Hydrolysis of starch into sugars Food 480 M. Gavrilescu, Y. Chisti / Biotechnology Advances 23 (2005) 471–499
