1. BIOLOGICAL
SOLUTIONS IN A
CHEMICAL
WORLD
Thomas Schäfer
Vice President, R&D
Philadelphia, August 2012
2. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer
Novozymes – The World Leader in Bioinnovation
• Largest market share of all players in Global enzyme market
Industrial Enzymes (47%) 2009 value: DKK ~ 16bn
• More than 60 years legacy in the Novozymes Danisco DSM Others Captive
business
• 2011 sales of DKK 10,510m 47% 21% 6% 16% 10%
(+8% in DKK, +10% in LCY, +7%
organic)
0% 20% 40% 60% 80% 100%
• 20 years sales growth CAGR of 8%
• EBIT: DKK 2340m (+11 %)
• ~ 14% of sales spent on R&D
• + 6,300 granted and pending patents
• + 5,500 employees Enzyme Business BioBusiness
• Global Organisation
Household Food & Feed & Micro- Biopharmaceutical
Bioenergy
• More than 700 products used in 130 Care Beverages other Tech. organisms ingredients
countries in over 30 different industries *A+B shares April, 2011
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3. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer
Novozymes’ Vision
• Less need for energy, water and chemicals
• Better utilization of raw materials
• Less CO2 emissions
• Ability to convert agricultural feedstocks
• Ability to produce food, feed, fibres, fuels & materials
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Central Working Hypothesis: Sugar/biomass can
gradually & partially replace fossile feedstocks
Fuel
Chemicals
Energy
…
• Where it “makes sense” (economy, LCA, customers)
• Where it is technically advantagous 4
5. 5 NOVOZYMES PRESENTATION
Biorefinery as central element
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Summary: Novozymes technologies deliver key
enablers for the biobased society
2 REFINING
1 INPUT 3 OUTPUT
The Sugar Platform
Microbial products for
BioAg
Platform
Enzymes Chemicals
5 4
Strong partnerships from
agriculture to consumer
companies
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1 INPUT: Three main technology BioAg platforms
Rhizobia
Biofertility
• Improve the uptake of N and P
Biocontrol
• Fungicides and bactericides
• Insecticides
• Herbicides
• Nematicides (future interest) LCO: OBSERVED BENEFITS
Bio-yield enhancement
• Yield improvement unrelated
to macronutrient acquisition
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2 Novozymes’ Central Technology: The Sugar Platform
• Cellulosic bioethanol drives our technology development
Starch Enzyme
process
Fermentable
sugars
Yeast Bio-
Fermentation ethanol
Waste Pre- Enzyme
treatment Cellulose
biomass process
process
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9. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer
Feb 2010: Novozymes Launches Cellic® CTec2
Allows production of
fuel ethanol from
biomass @ ca. USD
2.50 per gallon,
depending on
process
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Feb 2012: Next generation
Cellic CTec3
®
We can secure your plant’s
lowest total cost
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Feb 2012: Next generation
Cellic CTec3
®
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12. THE TECHNOLOGY IS READY AND
PRODUCTION IS BEING SCALED UP
2010 2011 2012 2013 2014
US Demonstration scale Commercial scale
Europe Demonstration scale Commercial scale
China Pilot scale Demonstration scale Commercial scale
Brazil Pilot scale Demonstration scale
SELECTED EXAMPLES 12
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M&G Breaks Ground for First Commercial Plant in
EUROPE
• Novozymes’ partner M&G begins
construction of the world’s first
commercial-scale cellulosic ethanol plant
• The plant will produce 13 million
gallons of ethanol per year from
biomass, and is competitive with 60-
70 USD/barrel oil
• The biofuels plant will be ready in 2012,
and is located in Crescentino, Northern
Italy
Pictures courtesy of M&G
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…while China accelerates:
Shengquan Group in July 2012…
• When China’s Shengquan Group starts
producing cellulosic ethanol in July
2012, it will be the first in the world to
do so on a commercial scale.
Novozymes’ partner Shengquan • More than that, the production will also
invests $100 million to market be cost-competitive with conventional
cellulosic ethanol ethanol, as the feedstock is a waste
product from Shengquan’s current
During the visit to Denmark of Hu Jintao, production.
President of the People's Republic of
China, Shengquan and Novozymes • Shengquan is a leading producer of
finalized an enzyme supply deal to furfural for resin production in the
market cellulosic ethanol. foundry industry. Furfural is produced
from corncob xylose, with the cellulose
from the corncob left behind as a waste
15. June 2012 product. Using Novozymes’ enzymes,
Shengquan will now be able to convert
http://www.novozymes.com/en/news/news- the cellulose into higher-value sugars
archive/Pages/novozymes-partner-shengquan- that can be fermented to ethanol.
invests-100-million-to-market-cellulosic-ethanol.aspx
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…as well as Brazil
• Today, June 23.05. 2012, GraalBio
announced plans to start production in
December 2013 of 82 million liters (22
Novozymes to supply first advanced million gallons) of advanced biofuels per
biofuels factory in Brazil year at a new factory in the Brazilian
state of Alagoas.
Brazilian bioenergy company GraalBio to
construct commercial scale cellulosic • The plant will produce cellulosic ethanol
ethanol facility in Brazil by 2013. from sugarcane bagasse and straw.
23. June 2012 • Novozymes will supply the necessary
enzyme technology
• Beta Renewables and Chemtex, both
part of Italian chemical group Mossi &
Ghisolfi (M&G), will provide other
process technologies and engineering.
http://www.novozymes.com/en/news/news- http://www.biofuelsdigest.com/bdigest/2012/05/24/graalbio
archive/Pages/Novozymes-to-supply-first-advanced- -investimentos-plans-to-invest-724-5-million-in-five-
biofuels-factory-in-Brazil.aspx cellulosic-ethanol-projects-in-brazil/
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3
The Sugar Platform is our link to OUTPUT
Starch Enzyme
process
Fermentable
sugars
Yeast Bio-
Fermentation ethanol
Waste Pre- Enzyme
treatment Cellulose
biomass process
process
Platform Technology:
enables production of a broad spectrum
of products
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3 Production of Renewable Chemicals
– a Good Fit to our Technology and our Vision
Yeast Bio-
Fermentation ethanol
Fermentable
sugars
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3 Production of Renewable Chemicals
– a Good Fit to our Technology and our Vision
Yeast Bio- Renewable
Fermentation ethanol chemicals
Fermentable
sugars
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3 Production of Renewable Chemicals
– a Good Fit to our Technology and our Vision
Yeast Bio- Renewable
Fermentation ethanol chemicals
Fermentable
sugars
Heterogenous Renewable
catalysis chemicals
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3 Partnering is essential for us
Yeast Bio- Renewable
Fermentation ethanol chemicals
Fermentable
sugars
Chemical Renewable
Catalysis chemicals
Novel
engineered
pathway Renewable
-- chemicals
Novel
Bioprocess/
Enzymes
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Novozymes’ biochemicals pipeline
Acrylic acid
Green polypropylene
C4 dicarboxylic acids Partner tbd
Novozymes’
biosolutions for
biochemicals Glycol
Glutamic acid
HMF/FDCA Partner tbd
BY BUILDING A BIOCHEMICAL INDUSTRY
PAVING THE WAY FOR THE BIOBASED SOCIETY
TOGETHER WITH OUR PARTNERS
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Novozymes’ biochemicals pipeline
Acrylic acid
Green polypropylene
C4 dicarboxylic acids Partner tbd
Novozymes’
biosolutions for
biochemicals Glycol
Glutamic acid
HMF/FDCA Partner tbd
PAVING THE WAY FOR THE BIOBASED SOCIETY HIGHLIGHTS AUGUST 2012
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Novozymes/Cargill partner with BASF
August 18th, 2012
Cargill & Novozymes started in 2008
BASF joins the cooperation now
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Case study: Novozymes’ Malic Acid project
Market potential
• Market size: 130 mUSD
• Market volume: 60 kMT
• Annual growth: 4%
• Applications: Food, beverages, cleaning
Produced from renewables agents
Starch or
Glucose Malic acid • C4 dicarboxylic acids are platform
biomass
chemicals:
Petro-based Maleic • can be further converted into
Malic acid
feedstock anhydride derivatives such as BDO, THF and
GBL which are used for a wide
Price in USD 2000 2010 variety of plastic, polymer and resin
applications
Malic acid 800/MT 2100/MT
Source: ICIS, SRI Consulting
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Overview of Novozymes’ Malic Acid project
Overall objective was to develop a microorganism that produces
commercially relevant levels of malic acid and secure freedom to
operate by timely filing of IP
Approach: Improve malic acid production in the novel, natural
malic acid producing filamentous fungus Aspergillus oryzae
NRRL 3488 by overexpression of cloned genes and classical
mutagenesis
Project targets were defined by a minimum volumetric
productivity and an overall Performance Factor (= Final product
concentration * Volumetric Productivity * g/g Yield on glucose)
Target performance must also be achieved in commercially
acceptable fermentation medium
MALIC ACID
STATUS AUGUST 2012
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Highest final malic acid concentration (Mutant M3)
and highest volumetric productivity (Mutant M4)
Major Acids Major Acids
350 300
Acid Concentration (g/L)
Acid Concentration (g/L)
300 250
250
200
200
150
150
100
100
50 50
0 0
0 24 48 72 96 120 144 168 192 0 24 48 72 96 120 144 168 192
Total C4
Time (hrs) Total C4
Time (hrs)
acids acids
Malic acid Malic acid
Data from un-optimized lab scale fermentations
Likelihood of further strain improvements is high
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Malic Acid as the preferred C4-platform chemical:
RECOVERY - crystal formation in fermentation
Mutant M3 Mutant M4
Crystal size varies with strain/lineage
Smaller crystals give higher viscosity
28. 29 NOVOZYMES PRESENTATION ACS 2012 Schäfer
Enzymatic modifications relevant for the
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chemical industry: > het/homogenous catalysis!
Esterification and ester • Application of lipases & cutinases in aqueous or non-
aqueous environment. Can be enantioselective. Also used for
hydrolysis polyester synthesis.
Nitrile hydrolysis • Hydrolysis to amide or carboxylic acid under mild conditions.
Can be enantioselective.
• Polymerization of aromatic structures by hydrogen
Free-radical polymerization abstraction using oxidoreductases
• Oxidation of aromatic side chains
Side chain oxidation using oxidoreductases
• Hydroxylation of aromatic or aliphatic carbon using
Hydroxylation oxidoreductases. Can be enantioselective
• Epoxidation of double bonds using lipases
Epoxidation or oxidoreductases
8/1
9/2
012
29. 30 NOVOZYMES PRESENTATION ACS 2012 Schäfer
Enzymatic modifications relevant for the
4
chemical industry: > het/homogenous catalysis!
Esterification and ester • Application of lipases & cutinases in aqueous or non-
aqueous environment. Can be enantioselective. Also used for
hydrolysis polyester synthesis.
Nitrile hydrolysis • Hydrolysis to amide or carboxylic acid under mild conditions.
• Proteases
Can be enantioselective.
• Lipases,
• Polymerization of aromatic structures by hydrogen
Free-radical polymerization esterases/cutinases
abstraction using oxidoreductases
• Oxido-reductases;
laccases,
• Oxidation of aromatic side chains
Side chain oxidation using oxidoreductases
peroxidases,
chloroperoxidase,
peroxygenase
• Hydroxylation of aromatic or aliphatic carbon using
Hydroxylation oxidoreductases. Can be enantioselective
• Amylolytic enzymes
• Epoxidation of double bonds using lipases
Epoxidation or oxidoreductases
8/1
9/2
012
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Novel experimental unspecific peroxygenase
catalyses hydroxylation reactions using only
hydrogen peroxide
• Opportunities:
• Peroxygenases provides oxyfunctionality to
a range of different substrates
Peroxygenases can be used i.e. in:
• Hydroxylation reactions
• Oxidation reactions
• Polymerisation reactions
• Regio and stereo selectivity can be very
high but depends on the actual substrate
• Peroxygenases operates under mild
conditions (pH 5-8; 30-50C), but is still
relatively stable towards auxiliary Aromatic epoxidation (e.g. naphthalene)
chemicals (e.g. cosolvents, detergents etc.) Alkane hydroxylation (e.g. n-hexane)
Epoxidation (e.g. styrene)
• Only waste product is water Ether cleavage (e.g. Tetrahydrofuran)
N-Oxidation (e.g. pyridine)
Sulfoxidation (e.g. dibenzothiophene)
Hofrichter (2010), Applied Microbiol. Halide oxidation (e.g bromide, Br-)
Biotechnology, 87
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Conclusions:
• The sugar platform is ready for implementation
• ethanol will be deployed first
• biochemicals catching up…also from biomass
• Market pull for renewable chemicals
• ”Untraditional partnerships”
• combine agriculture, biology & chemistry and building new value chains
• new growth markets for grain processors, biotech companies, chemical
companies and consumer goods companies
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