Biotechnology DOI 10.1002/biot.201100069 Biotechnol. J.

2012, 7, 176–185
Journal

Biotech Highlight

Perspective on opportunities in industrial biotechnology

in renewable chemicals

Brent Erickson1, Janet E. Nelson2 and Paul Winters1,*

Received 24 May 2011
1 Biotechnology Revised 22 July 2011
Industry Organization (BIO), Washington, DC, USA
2 URS Accepted 12 August 2011
Corporation, Germantown, MD, USA

Keywords: Biorefinery · Chemical building blocks · Industrial biotechnology · Metabolic engineering · Synthetic biology

1 Introduction with potentially higher returns. Early efforts to lay

a roadmap for biological production of chemicals
Industrial biotechnology encompasses the applica- from renewable sugars focused on those that would
tion of biotechnology-based tools to traditional in- provide co-products for integrated biorefineries
dustrial processes (“bioprocessing”) and the man- producing biofuels and bioenergy as the primary
ufacturing of bio-based products (such as fuels, product. A growing number of companies are now
chemicals and plastics) from renewable feedstocks. focusing on specialty chemicals as an entry point to
Microbes, microorganisms, enzymes and their ge- build the bio-based economy.
netic engineering form the basis of a suite of tech-
nologies and processes that a diverse group of com-
panies, researchers and scientists are seeking to 2 Microbial processes: A familiar tool
develop for commercial use.
Mankind has been using microbial processes Currently there are many examples of microbial
for producing foods and other goods since Neolith- processes and renewable agricultural materials
ic times. But the evolution of our ability to manipu- used in producing material goods, including cheese
late microbial genomes has revolutionized the field making and other fermentations. But an increased
of biotechnology and produced a rapid increase in understanding of, and ability to restructure, fer-
innovation for industrial uses. In most cases, in- mentation processes and microbial metabolic sys-
dustrial biotech tools allow industry to develop new tems has allowed researchers to expand the appli-
industrial manufacturing processes that are clean- cation and engineering of microbes and enzymes
er and better for the environment with reduced into a broader variety of industrial processes. These
economic costs. Industrial biotech represents the processes can often construct products faster and
third wave in biotechnology, following innovation in a resource- and environmentally sustainable
in the health care and agricultural sectors. manner at reduced cost, while using less energy [1].
While biofuels have attracted a great deal of in- Further, industrial biotechnology can reduce car-
terest among the public, press and policy makers, bon emissions through improved process efficien-
renewable chemicals represent another major op- cy, the displacement of fossil fuels and petroleum-
portunity to commercialize industrial biotechnolo- based materials, and the creation of closed loop
gy in existing markets, at lower capital costs, and industrial systems that eliminate waste [2]. Indus-
trial biotechnology’s enabling of integrated biore-
fineries that produce multiple product and value
Correspondence: Brent Erickson, Biotechnology Industry Organization streams is viewed as potentially transforming the
(BIO), Industrial & Environmental Section, 1201 Maryland Ave., SW, economics of industrial production [3]. New tech-
Suite 900, Washington, DC 20024, USA
niques, such as synthetic biology, can potentially
E-mail: [email protected]

Abbreviations: BDO, 1,4 butanediol; DOE, Department of Energy; PDO, 1,3

propanediol; PHA, polyhydroxyalkanoate; PLA, polylactic acid; RFS, Renew- * Additional correspondence: Paul Winters
able Fuel Standard E-mail: [email protected]

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Biotechnol. J. 2012, 7, 176–185 www.biotechnology-journal.com

speedup the development and commercialization cated or chemically reconstructed, researchers and
of industrial biotech processes, making them at- companies are beginning to design and create nov-
tractive and affordable to manufacturers. el microbial systems that perform multistep
Living systems manage their chemistry more processes to metabolize renewable sugars into
efficiently than man-made chemical refineries, and chemical building blocks, monomers, polymers and
most of the wastes they generate are recyclable or acids. Synthetic biology has also enabled the cre-
biodegradable. Nature’s enzyme-based processes ation of novel enzymes that can work in multi-step
operate at lower temperatures, and produce less biocatalysis of chemicals, such as for pharmaceuti-
toxic waste and fewer emissions than conventional cals (see for instance http://www.epa.gov/gcc/pubs/
chemical processes. Because enzymes have precise pgcc/winners/grca10.html). The reconstruction of
chemical selectivity, they may also use less purified DNA strands from their chemical base elements
raw materials. These characteristics can be exploit- according to computer-aided designs for metabolic
ed to increase the energy efficiency and improve platforms has given rise to the term “synthetic
the environmental profile of chemical reactions biology.”
used in manufacturing [1]. Many, but not all, industrial biotechnology ap-
Industrial biotechnology companies use life- plications involve the harnessing of nature’s en-
science techniques to find and improve nature’s zymes. Industrial biotechnology can use extracted
enzymes or develop diverse microbial systems – enzymes or whole cell systems to accomplish a
from bacteria, yeasts, and fungi to marine diatoms task. The recent and dramatic advances in biotech-
and protozoa – for use in industrial applications. nology techniques are why so many biocatalytic
Companies search for enzyme-producing micro- tools are becoming available to be used in industri-
organisms in the natural environment (bio- al applications.
prospecting) and then use genomic and proteomic
studies and tools to fish for genes that express en-
zymes with specific biocatalytic capabilities. Once 3 Industrial biotechnology finds a home:
identified, enzymes can be characterized for their Enabling the biorefinery
ability to function in specific industrial processes.
If necessary, enzymes can be improved with Biorefineries are dedicated facilities that convert
biotechnology techniques, such as gene transfer, the sugars, oils and proteins derived from renew-
gene shuffling, directed evolution or metabolic en- able biomass into biofuels, chemicals and materials
gineering. such as plastics and polymers. The concept is mod-
Once useful enzymes are discovered and im- eled on the petroleum refinery, in which crude oil
proved, they can be produced in commercial quan- is converted into fuels and chemicals that provide
tities using either naturally occurring or genetical- multiple product and revenue streams. Just as a
ly enhanced microbes (GEMs). Currently, it is com- barrel of oil can be broken down into constituent
mon for genetically engineered microbes (for ex- parts that add up to more by volume and value than
ample, bacteria or yeast improved through gene the original barrel, the objective of a biorefinery is
shuffling) to carry out the fermentation. Fermenta- to develop as many product and value streams as
tion and reproduction of the organism are normal- possible from biomass. This optimization and effi-
ly done in contained stainless steel fermentation ciency are essential for economic and environmen-
tanks or systems similar to those that produce hu- tal sustainability.
man therapeutic proteins or bulk yeast for the There are many existing biorefineries in the
brewing industry. United States that process corn into sugars (such as
Biotechnology enables scientists to maximize high fructose corn syrup), oils, animal feeds and
the effectiveness and efficiency of enzymes and food ingredients (such as xanthan gum). More than
microbes or to custom tailor the specificity of en- 200 ethanol biorefineries have been built, primari-
zymes, improve catalytic properties or broaden the ly using the corn’s starch for biofuel and the re-
conditions under which enzymes can function so maining protein and fat for animal feed and veg-
that they are more compatible with existing indus- etable oils. Some of these first-generation biore-
trial processes. Scientists can also give new manu- fineries are looking to create product and value
facturing capabilities to these microscopic work- streams from the cellulosic bran in the kernel and
horses by genetically enhancing them so they make the stover (leaves and stalks) of the corn plant for
enzymes that would otherwise have to be produced additional product and value streams.
by microorganisms that are expensive or too There has been rapid growth in construction of
finicky to cultivate in industrial quantities. With li- corn ethanol biorefineries since 2005, when the Re-
braries of bioinformatic material that can be repli- newable Fuel Standard (RFS) was first enacted,

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due to the economic opportunity presented by high

oil prices and the phase out of methyl tertiary butyl
ether (MTBE) in gasoline [4]. Figure 1 details this
growth. The RFS was enacted in the United States
in recognition of the national security implications
of overreliance on foreign supplies of petroleum,
the energy security implications of oil’s price
volatility, and the ongoing environmental costs of
fossil fuel use. Corn ethanol biorefineries that co-
produce animal feed (distillers grains, corn gluten
meal and corn gluten feed) and corn oil have very
simple economic models that displace some use of
petroleum for fuel and feed. Much more sustain-
able models that fractionate the corn kernel for ad- Figure 1. Growth of corn ethanol refining, 2000–2011. Construction of
ditional value streams are now being developed, new ethanol biorefineries and expansion of existing production capacity
and use of renewable energy sources for power and accelerated following the adoption of the nation’s first RFS in 2005.

electricity generation are in development. Petrole-

um’s price volatility affects the entire value chain
for petroleum refineries, pushing industry to seek product and value streams. Biorefineries must seek
replacements for the “entire barrel of oil.” to maximize the use of biomass, recycle waste
There are a growing number of demonstration streams as input for new product streams, and uti-
and pilot-scale biorefineries across North America lize heat from primary processes as energy for sec-
that plan to use locally produced biomass, includ- ondary processes. Biotech routes to a wide array of
ing starches such as sorghum; cellulosic feedstocks chemical products are being developed for integra-
such as grasses, woody biomass (fast-growing trees tion into biorefineries, allowing for diversification
and shrubs or forestry residues); municipal solid of product and value streams.
waste; and algae. Cellulosic biomass is the most
abundant source of carbon, and its ubiquity makes
it potentially the lowest-cost source of renewable 4 Early estimation:
sugars for biorefineries. A great deal of industrial Value-added chemicals from biomass
biotech research and development has focused on
enzymatic conversion of cellulose to sugars and In 2004, the U.S. Department of Energy (DOE) con-
consolidated metabolic bioprocessing of cellulose ducted an initial screening and categorization of
to higher value molecules. renewable chemicals that could be co-produced as
The challenge for any biorefinery is to establish side streams of biofuels and bioenergy [5]. The
a reliable supply chain for sufficient feedstock at a analysis yielded a list of 30 potential monomers
stable price. In the United States, there are well-es- with up to six carbon atoms that could be ferment-
tablished supply chains for pricing and delivery of ed from the sugars in biomass and serve as build-
corn. Collection, harvesting, storage and transport ing blocks for more complex chemicals – as inter-
of other biomass feedstocks – including corn stover mediates, novel products, or direct replacements
– are in development, but rely to a large degree on for petroleum products. Twelve of these chemicals,
expectations that market demand among bio- listed in Table 1, were designated as top targets for
refineries will exist. Biotechnology is playing an further research and development within industri-
important role in increasing productivity for many al biotechnology.
biomass feedstocks, utilizing the same tools that The DOE study noted clearly that its choice of
have enabled increased production of corn and soy, biorefinery products was limited to the compounds
namely pesticide and herbicide resistance. Genetic with three to six carbon molecule chains (C3–C6)
engineering tools applied to commercial produc- derived directly from the sugars in biomass. These
tion of microbes are being applied to algae – building block chemicals can be produced biologi-
including gene shuffling, gene transfer, and even cally and then upgraded through traditional chem-
synthetic biology – to increase the productivity of istry to form intermediate ingredients for common
target strains. consumer products. Economic costs and potential
Biorefineries are expected to follow common markets were additional considerations in the
business imperatives of industrial ecology. To re- choice of the final top 12.
main economically competitive, they must continu- However, a more diverse portfolio of products
ally innovate, increase efficiency, and develop new from biomass is possible. Aromatics produced from

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Table 1. Top value-added chemical building blocks from biomassa)

Building blocks Molecular formula Some potential uses

1,4-Diacids C4H6O4 Solvents, fibers such as Lycra
(succinic, fumaric and malic)
2,5-Furan dicarboxylic acid C6H6O3 PET analogs with potentially new properties (bottles, films, containers)
3-Hydroxy propionic acid C3H6O3 Contact lenses, super absorbent polymers for diapers, carpet fibers
Aspartic acid C4H7NO4 Chelating salts, sweeteners
Glucaric acid C6H10O8 Solvents, nylons
Glutamic acid C5H9NO4 Monomers for polyesters and polyamides
Itaconic acid C5H6O4 Copolymer in styrene butadiene polymers (provides dye receptivity for
fibers), nitrile latex
Levulinic acid C5H8O3 Fuel oxygenates, solvents, replacement for bisphenol A in polycarbonate
synthesis
3-Hydroxybutyrolactone C4H6O3 Intermediate for high-value pharmaceutical compounds
Glycerol C3H8O3 Personal and oral care products, drugs and pharmaceuticals, foods and
beverages, and polyether polyols (for polyurethane)
Sorbitol C6H14O6 Antifreeze, PET-like polymers such as polyethylene isosorbide terephthalates
(used for hot-fill bottles)
Xylitol/arabinitol C5H12O5 Non-nutritive sweeteners, unsaturated polyester resins
a) Adapted from [5]. PET, polyethylene terephthalate.

lignin can be used for polymers and surfactants, tivity would approach $15 billion. Producing and
polysaccharides can find a market in paper and transporting biomass to biorefineries could gener-
metal finishing, and plant oils have well-estab- ate an additional $120 billion in economic activity,
lished uses [6]. while conversion of biomass to heat and power
Since 2004, when the DOE conducted its analy- could also be worth $65 billion [8].
sis of sugar-derived chemicals, biotech companies According to a 2011 report from investment an-
have developed economical fermentation path- alysts Clean Edge, the ethanol and biodiesel indus-
ways to a wider array of building block chemicals tries reached a combined wholesale value of
as well as direct metabolic pathways to intermedi- $56.4 billion, representing more than 27.2 billion
ate chemicals. The speed of development of gallons of production, in 2010 and will grow to
biotechnology has dramatically altered the eco- $112.8 million by 2020 [9].
nomics of chemical production, making it an at- The World Economic Forum report notes that
tractive production opportunity in its own right mandates for biofuel production around the world
rather than a co-production strategy [7]. As the drive the market for biofuels, while economics and
economics of bioprocessing improve and the price sustainability criteria drive the smaller market for
of alternative petrochemicals varies, the markets renewable chemicals. At present, chemical compa-
for potential end uses also change, making it prof- nies have only sought to replace selected chemical
itable to develop new tools. intermediates already in their portfolio, rather than
seek markets for novel chemical compounds that
might best be suited to the inherent properties of
5 Potential market size and value biomass [8]. The strategy is limited to replacements
for platform chemicals of petrochemicals with bio-based chemicals that
offer identical functionality and performance.
A 2010 report from the World Economic Forum es- The markets for microbes, microbial products
timated that by 2020 the market for biofuels, bio- and enzymes have been estimated by market fore-
based bulk chemicals and plastics, and bioprocess- casting firm BCC Research. The global market val-
ing enzymes would approach $95 billion. The mar- ue for microbial products – used as biopesticides in
ket for technology to increase agricultural produc- agriculture as well as in chemical production – is an

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estimated $156 billion in 2011 with an expected in- resulted from the direct physical or chemical pro-
crease to more than $259 billion in 2016, for a com- cessing of biomass (cellulose, starch, oils, protein,
pound annual growth rate of 10.7%. The underlying lignin), while the next wave of products are being
market for microbes is projected to reach $6.8 bil- indirectly processed from carbohydrates by
lion in 2016 from its estimated value of nearly biotechnologies such as microbial and enzymatic
$4.9 billion in 2011 [10]. processing.
The global market for industrial enzymes was Early examples of commercially available bio-
$2.9 billion in 2008, $3.1 billion in 2009, and $3.3 bil- products include several bio-based plastics en-
lion in 2010 and expected to reach $4.4 billion by abled by industrial biotechnology, and these are
2015, achieving a compound annual growth rate of shown in Table 2. These plastics, while having many
6%, according to BCC Research. Within that esti- potential market uses, have been introduced in a
mate, technical enzymes (e.g., for biofuels) were few select markets where biodegradability or dis-
valued at just over $1 billion in 2010 and projected placement of petrochemicals offers a premium
to reach $1.5 billion in 2015. Food and beverage en- price or competitive advantage. The early market
zymes (e.g., for milk and dairy products) had an es- successes and failures of these products have
timated value of $975 million in 2010, reaching shown that price competitiveness and performance
$1.3 billion by 2015 [11]. are as critical to market success as environmental
The Organization for Economic Co-operation sustainability.
and Development projects that worldwide plastic • 1,3 Propanediol (PDO): Bio-derived PDO is
consumption will grow from 250 000 kilotons cur- fermented from corn sugar using a biotech
rently to about 1 million kilotons 2020. Five petro process. The PDO monomer is separated from
polymers currently make up two thirds of the plas- the fermentation broth and then available to be
tics market: low-density polyethylene (LDPE), used in direct product formulations or as an in-
high-density polyethylene (HDPE), polypropylene, gredient in polymers. Over a dozen products can
poly-vinyl chloride (PVC) and polyethylene be made using bio-derived PDO as a key ingre-
terephthalate (PET) [12]. Bio-based analogs to dient. Zemea® and Susterra® propanediol are
these plastics and novel bioplastics are being de- two grades of 100% renewably sourced Bio-
veloped, either through fermentation of building PDO™, manufactured by DuPont Tate and Lyle
blocks [such as ethanol or polylactic acid (PLA)] Bio Products (http://www.duponttateandlyle.
or direct metabolic production of new types of com/). Zemea® propanediol has been developed
plastics [such as polyhydroxyalkanoate (PHA)], for use in cosmetics, personal care and home
and these could eventually shift market con- cleaning products, offering high purity, low irri-
sumption [7]. tation and sustainability to formulators and
Currently, global bioplastics consumption rep- manufacturers. Susterra® propanediol is used in
resents 1000 kilotons, or 0.4% of total plastics con- aircraft deicing, antifreeze and heat-transfer in-
sumption. The bioplastics industry expects to grow dustrial fluids as well as unsaturated polyester
rapidly, reaching 3450 kilotons annually by 2020 resins and polyurethanes. Susterra® propanedi-
[12]. ol is a key ingredient for DuPont™ Sorona®
polymer used in carpets. On a pound-for-pound
basis, producing bio-based PDO consumes 38%
6 Success stories: Large-scale less energy and emits 42% fewer greenhouse gas
commercialized bio-based products emissions compared to petroleum-based pro-
panediol or propylene glycol.
While petroleum still dominates today’s industry, • Polylactic acid (PLA): Ingeo® brand PLA is the
there is a strong and growing interest in converting world’s leading biopolymer player(http://www.
underutilized biological materials into useful prod- natureworksllc.com/); compared to the other
ucts. With increasing end-use market drivers for biodegradable polyesters, PLA is the product
bio-based chemical products and applications, nu- that at the present has one of the highest poten-
merous opportunities are emerging to address in- tial due to its availability on the market and its
dustrial needs through the production and pro- low price. Currently, this proprietary PLA
cessing of biological materials. Bio-based materials biopolymer, marketed under the Ingeo trade-
represent a significant and growing market with an mark, has been shown to be competitive on a
extensive range of products. Currently available cost and performance basis with traditional
bio-based products include commodity and spe- plastics. It has superior environmental charac-
cialty chemicals, fuels, and materials. The early teristics, and established global market chan-
commercially successful products have generally nels with over 20 applications in more than

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Table 2. Early commodity scale bioproducts

Chemical Companies Brand name(s) and Application

annual production
1,3 Propanediol (PDO) DuPont Tate Zemea® and Susterra® Cosmetics, personal care and home cleaning products,
C3H8O2 & Lyle – 135 million lbs. aircraft deicing, antifreeze and heat-transfer industrial fluids
DuPont™ Sorona® carpet
Polylactic acid (PLA) NatureWorks Ingeo® – 300 million Food grade plastics – utensils, wrap, containers, packaging
C3H6O3 LLC lbs.
Polyhydroxyalkanoate Metabolix Mirel® from Telles Packaging for cosmetic products and food products,
(PHA) – 110 million lbs. injection-molded durable goods such as cell phone cases,
CH2[OCH(R)(CH2)xCO]nCH2 SyntheZyme hand-held devices
Polyethylene Braskem Green polyethylene Food packaging, drink bottles, plastic bags, trash
C2H4 – 400 million lbs. containers, car parts
Polyols BiOH BiOH polyols Foam for furniture, bedding, automotive, carpet,
HO-R-OH construction, coatings, sealant, adhesive, and elastomers

70 000 store shelves globally and over 100 mil- products. However, the ultimate commercial suc-
lion pounds in annual sales volume. cess of bioplastics, the role of sustainability factors
• Polyhydroxyalkanoate (PHA): Another exam- with consumers and retailers, and the competitive
ple of a commercially successful bio-derived advantages to be gained by switching to biomass-
polyester plastic is a biodegradable PHA. This derived chemicals relies upon the three factors:
renewable plastic based on sugar has high ther- (i) economics, (ii) performance, and (iii) environ-
mal stability, as well as superb biodegradability, mental factors. These factors are interdependent,
and has been demonstrated in a very broad as shown in Fig. 2 and detailed below.
range of applications including molded prod- • Economics: The market price of commodity
ucts, films, foam, and fiber. PHA is being devel- bioproducts depends on two key factors: the cost
oped by companies such as Metabolix and Syn- of the raw material, and the cost of the process-
theZyme. It has an annual market potential of ing technology. A driving force for production of
over $5 billion (http://www.mirelplastics.com/, many bio-based products has been a search for
http://www.synthezyme.com). alternatives to fossil fuels, which have been sub-
These three examples represent successful market ject to price volatility affecting the profit mar-
penetrations for large-scale bio-based industrial gins of downstream products. In many cases,
bio-based products received a premium price or
subsidy when they were introduced to the mar-
ketplace. The long-term growth of bio-based
products hinges on a critical need to secure
large quantities of biomass at low costs. All fac-
tors that affect feedstock such as price, variety,
pretreatment, land-use, competition from crude
oil, transportation logistics, international supply
chains are key. Reducing the costs of producing
bio-based products also depends strongly on re-
ducing the costs of processing technology. Today
only a small fraction of available biomass is
used to produce bio-based chemicals due to
these high conversion costs. Research and de-
velopment is costly, pilot and demonstration
plants have very high investment costs, and in-
Figure 2. Factors determining competitive advantages for biomass-
frastructure to get the agricultural raw materi-
derived chemicals. Commercial success and competitive advantages for
biotechnology enabled, biomass-derived chemicals relies upon the three als to the production sites is critical. The long-
interdependent factors, 1. economics, 2. performance, and 3. environmen- term growth of bio-based products will depend
tal factors. on the development of cost-competitive tech-

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nologies – which in many cases is greatly im- Table 3. Near-term commercial-scale bio-based chemicals
proved by scale – and access to diverse markets. Chemical Companies Application
• Performance: Performance is another aspect of
the new bio-based product or technology that Succinic acid Myriant Flavorings, dyes, perfumes,
shapes its market acceptance. Bio-based prod- BioAmber lacquers
ucts must offer equal if not better performance DSM
than petroleum-based products to be accepted 1,4 Butanediol Genomatica Spandex, povidone-iodine
by consumers and retailers. Advances in re-
Isoprene Genencor Rubber, adhesives
search continue to improve the desired proper-
Amyris
ties and performances of bio-based products.
Increasingly, niche markets will be sought for a Isobutanol Gevo Solvents, paint, biofuel
wide array of custom-engineered products, such
Acetic acid ZeaChem Ethanol
as those based on chiral compounds, which are
not directly available from petroleum products Polyethylene Dow Plastic bags
without expensive conversion steps, but may be Isosorbide Roquette, ADM, Polyesters, surfactants,
easily and directly produced by a biotechnology Cargill pharmaceuticals
route.
• Environmental factors: Industrial biotechnol-
ogy can offer processes that have a better car-
bon footprint than petrochemicals. In addition • Succinic acid: Succinic acid, commonly re-
to moving away from petroleum, many of the ferred to as amber acid, is a key building block
bio-processes actually consume CO2, directly for a wide range of secondary chemicals used in
reducing greenhouse gas emissions and aiding the chemical, pharmaceutical, food and agricul-
in the fight against global warming. The produc- tural industries. Until recently, all succinic acid
tion processes are also often cleaner than typi- was produced from petroleum feedstocks. Of-
cal petrochemical processes, using less energy fering cost-competitiveness and superior func-
and generating less waste than conventional tionality and performance, bio-derived succinic
synthetic processes. acid can replace conventional petroleum-based
succinic acid, substitute for other chemicals like
adipic acid in applications such as production of
7 Near-term opportunities: Bioconversion polyurethanes, and serve as the starting materi-
replaces chemical processes al for the production of high-value, high-volume
chemicals. Myriant (http://www.myriant.com)
Bio-based products fall into three categories: com- and BioAmber (http://www.bio-amber.com)
modity chemicals, specialty chemicals, and materi- have provided breakthrough biotechnology in
als. Many of these products, such as cellulose, commercial production. These companies pro-
starch, oils, protein, lignin, and terpenes result duce succinic acid biochemically from glucose
from the direct physical or chemical processing of using a genetically engineered organism [13].
biomass. Others are indirectly processed from car- The bio-based succinic acid is cost competitive
bohydrates by biotechnologies such as microbial and offers superior functionality or perform-
and enzymatic processing. More and more bio- ance with a better environmental footprint.
based chemicals are becoming cost competitive • 1,4 butanediol: BDO is a key chemical interme-
and represent a near-term opportunity for replace- diate with a large range of applications includ-
ment of petrochemicals with renewable resources. ing polyesters, polyurethanes, co-polyester
Near-term strategies are dominated by fermenta- ethers, and other co-polymers. BDO is a chemi-
tion of sugars through microbial processes for pro- cal building block with a $3 billion market and is
duction of commodity chemicals. Bio-based chem- used to make products such as spandex and au-
ical production uses metabolic engineering to con- tomotive plastics. Genomatica (http://www.
struct organisms that make high-value, high-puri- genomatica.com) has developed technology and
ty, renewable sugar-based chemicals, such as manufacturing processes that can make Bio-
succinic acid, 1,4-butanediol (BDO), isobutanol, BDO, i.e., exactly the same chemical, from sus-
and acetic acid. To date, however, commercial tainable ingredients rather than crude oil or
development of chemicals from cellulosic feed- natural gas hydrocarbons [14]. Genomatica’s
stocks has lagged, although some companies are technology allows it to rapidly develop organ-
at demonstration and pilot scale, as shown in isms and cost-effective manufacturing process-
Table 3. es for intermediate and basic chemicals. Geno-

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matica’s technology also offers the potential to • Acetic acid: Acetic acid is a commercial product
use a range of feedstocks, including convention- and an intermediate building block for the pro-
al sugars, cellulosic biomass and syngas. duction of a vast array of chemical compounds.
• Isoprene: Many bio-based chemicals have Acetic acid is salable to various manufacturing
demonstrated a major potential to reduce the industries for the production of film, bottles and
tire and rubber industry’s dependence on oil fibers, among other products. Global demand
and natural rubber. A research collaboration be- for acetic acid is 14.3 billion pounds per year.
tween Genencor® Division of Danisco (http:// Recently ZeaChem Inc. (http://www.zeachem.
www.genencor.com) and Goodyear Tire and com), a developer of biorefineries for the con-
Rubber Company has resulted in the production version of renewable biomass into fuels and
of BioIsoprene, a synthetic cis-polyisoprene. chemicals, has produced bio-based acetic acid
The enzyme isoprene synthase has only been using an acetogen, a naturally occurring organ-
identified in plants, but production strains of ism. The bio-derived acetic acid is at the purity
microorganisms are not efficient in expression concentration level of the traditional product,
of plant genes. In this example, synthetic biolo- and has successfully demonstrated the com-
gy allowed the construction of a gene that en- mercial scalability of the company’s front-end
codes the same amino acid sequence as the fermentation process.
plant enzyme but is optimized for expression in These advances in bio-based chemical production
engineered microorganisms [15]. Although the illustrate that attention among developers of cellu-
technology will not be full scale for several losic biomass is shifting from ethanol to higher-val-
years, it has proved to be a strategic bio-based ue industrial chemicals. However, many technolog-
alternative that has broad applications as a re- ical impediments remain. Each pathway has its
placement for natural rubber, adhesives, and own set of advantages and disadvantages. For ex-
fuel. This is a classic example of the drive to- ample, operating conditions for biological conver-
wards sustainability; the process offers a real sions are relatively mild as most reactions are done
possibility for obtaining meaningful quantities at ambient temperatures and pressures. Chemical
of a renewable chemical that replaces a scarce transformations can operate at high throughput,
natural resource. although they sacrifice conversion specificity. Cer-
• Isobutanol: Isobutanol is a building block tain processing technologies are well established,
chemical that can be used in solvents, rubber, while others show promise but will require addi-
and transportation fuels, each of which consti- tional refinement or research before they come
tute multi-billion dollar markets. Through stan- into commercial use. More research is needed to
dard chemistry, isobutanol can be used as an in- expand the suites of potential pathways, to increase
gredient in nearly 40% of traditional chemicals our understanding of all the technical barriers, and
(such as butenes, toluenes and xylenes) as well to evaluate which bio-based feedstock materials
as many transportation fuels. Used as a solvent, will hold the most promise in an integrated biore-
isobutanol appears in paints and cosmetics such finery. As new or improved low-cost processing
as nail polish. The solvent, rubber and fuel in- technologies are developed, this will drive which
gredients markets are each worth several billion bio-based products become available.
dollars. Gevo (http://www.gevo.com) is now pro- Critical factors for successful bio-based chemi-
ducing this chemical building block from sugars cal production will rely on low capital expenditures
by fermentation. They have developed an Inte- (CAPEX) and ongoing cost for running a product
grated Fermentation Technology (GIFT) that (operating expenditures, OPEX) as well as contin-
combines genetically engineered yeast with a ued market adoption. Expansion of bio-based in-
continuous separation process to screen the dustrial production requires an overall scale-up of
isobutanol from the fermentation broth, allow- manufacturing capabilities, diversification of pro-
ing the yeast to survive longer. Using synthetic cessing technologies, and reduction of costs. The
biology, Gevo has engineered a yeast to concen- processing technologies of refineries tend to im-
trate on production of isobutanol by blocking prove over time, and eventually raw material costs
production of ethanol and acetic acid [16]. As tend to become the dominant cost factor. Here,
volatility in petroleum prices can have a signif- biorefineries have a significant advantage over pe-
icant impact on these markets, bio-derived troleum refineries as the availability and prices of
isobutanol can serve as a drop-in replacement sustainable, renewable biomass may be more sta-
for petroleum, offering stability in pricing and a ble and predictable.
potential savings of more than $1 on each gallon
produced.

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Biotechnology Biotechnol. J. 2012, 7, 176–185
Journal

8 Future value-added bio-based chemicals: Table 4. Future potential value added biobased chemicals

Driven by synthetic biology Chemical Companies Application

Recent advances in metabolic engineering and bio- Terpenes Allylix Fragrance, flavoring,
chemical pathway analysis make it possible to effi- anti-fungal, anti-viral,
ciently manipulate the biosynthetic pathways of insect repellents
microorganisms. Using functional genomics and Levulinic acid, DuPont Tate & Plasticizers, solvents,
genetic engineering to increase chemical yield and polyols Lyle polyester resins
selectivity makes microbial production more eco- Segetis
nomically competitive with traditional production
Hyalurionic acid, OPX Bio Acrylics, coatings, textiles,
methods. The combination of modern genetics and
3-HPa) detergents
protein engineering will continue to provide new
biocatalysts for improved synthesis or conversion Adipic acid Verdezyne Fibers, plastics
of biofuels, renewable chemicals, specialty chemi- Surfactants Modular Genetics Foaming agents,
cals, and other bioproducts. Small start-up biotech- emulsifiers, dispersants
nology companies are developing synthetic biology
applications that can significantly speed introduc- Itaconic acid Itaconix Pigments, stabilizers
tion of bio-based chemicals to markets in food in- Polypropylene Novozymes, Plastic
gredients, pharmaceutical intermediates, specialty Braskem
chemicals, and biofuels [7].
a) 3-HP, 3-hydroxy propionic acid.
Terpenes provide one among many examples
where companies are in early stages of commer-
cializing technology or new products. A group of
natural products called terpenes are produced by lignocellulosic plant materials are likely to become
plants in minute quantities and serve a number of cost competitive with petroleum fuels. But already,
different functions from fragrances, to food ingre- bio-based technologies such as enzyme catalysts
dients, to pharmaceuticals. Historically, terpenes are promising replacements for industrial chemical
have been too expensive to produce through tradi- processes. And, low-volume, high-value chemical
tional manufacturing processes such as chemical production from biomass offers an opportunity to
synthesis or extraction. Recently, Allylix has devel- commercialize biotechnology applications in
oped a proprietary technology that allows it to cost- ready-made markets for existing chemicals, if qual-
effectively produce commercial volumes of various ity, price and performance are equal to reference
terpenes. The Allylix proprietary metabolic engi- petrochemicals. In a few cases, bio-based products
neering fermentation platform produces a sustain- may see a price premium for performance.
able, stable supply of terpenes with a step change This opportunity to commercialize industrial
in the cost of production, and has thus opened the biotechnology in existing markets is being driven
use of terpenes broadly across the market. Addi- by both a technology push and industry and mar-
tional examples are listed in Table 4. ket pulls. Rapid and unprecedented progress in the
key technologies of the modern biological sciences,
such as metabolic engineering and synthetic biolo-
9 The future of industrial biotechnology: gy, are driving bio-products and processes to be
Challenges and opportunities more efficient and cost competitive, and are fueling
innovation in the chemical industry. Although it
Industrial biotechnology is much larger than just a takes time to commercialize new technology (from
new source of liquid fuels. Significant benefits can process development to feedstock utilization to
be realized by switching significant production that consumer), the application of new biotech tools to
is currently dependent on fossil resources to bio- traditional chemical processes is shortening the
logical sources. timeline. Renewable chemicals and bioproducts
A wide range of bio-based industrial products from biorefineries continue to grow rapidly and
and technologies continues to penetrate diverse in- gain increased market share.
dustrial markets. Ethanol and other oxygenated A particularly encouraging phenomenon is the
chemicals derived from fermentable sugars have extent of industry pull for industrial biotechnology
served as key precursors in the marketplace to oth- products. There are now plenty of examples of in-
er industrial chemicals traditionally dependent on dustry not only employing bioproducts, but creat-
petroleum. In the long term, with advances in ge- ing more demand for these and new products. For
netic engineering, large-scale fuel production from example, the maturation of bioplastics from the

184 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Biotechnol. J. 2012, 7, 176–185 www.biotechnology-journal.com

laboratory bench to large-scale production is find-

ing new industry customers, particularly in the au-
tomotive and consumer electronics industries. The Brent Erickson is executive vice presi-
development of highly efficient biorefineries that dent of the Industrial and Environmen-
integrate production of numerous bio-based prod- tal Section at the Biotechnology Indus-
ucts could help reduce costs and allow bio-based try Organization (BIO). Mr. Erickson
products to compete more effectively with petrole- holds a B.S. in Biology and an M.A. in
um-based products on price. International Studies. He served as
While industrial biotechnology offers a clear legislative director for U.S. Senator and
value proposition, a number of hurdles need to be Republican Whip Alan K. Simpson
addressed to fully realize the commercial potential (R-WY). Mr. Erickson also serves as a
of bio-based products and chemicals over the com- member of the board of directors of the Western Research Institute,
ing decade. Cost-effective solutions will depend on the advisory board of the Energy Biosciences Institute (EBI), and the
continued research and development, government Scientific Advisory board of the Synthetic Biology Engineering Re-
and private sector investment, establishment of search Center (SynBERC).
new supply chains for renewable and sustainable
biomass feedstocks, and market acceptance tied to
compatibility with existing infrastructure. Fortu-
nately, we seem to be on the path to commercialize Dr. Janet Nelson is a Director of Busi-
these solutions and to build a worldwide bio-based ness Development for URS Corpora-
economy. This is good news for business, con- tion, currently supporting program
sumers and our environment. growth at the National Energy Technol-
ogy Laboratory (NETL) and providing
The authors declare no conflict of interest. project management support for sever-
al activities. Dr. Nelson holds a Ph.D.
in Chemistry from Caltech and has over
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