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BIOLOGICAL
    SOLUTIONS IN A
    CHEMICAL
    WORLD




Thomas Schäfer
Vice President, R&D
Philadelphia, August 2012
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

                                                                                                                                               2
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

                                                                            3
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer


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           NOVOZYMES PRESENTATION




    Biorefinery as central element
8/19/2012       NOVOZYMES PRESENTATION ACS 2012 Schäfer


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


                                                                                                  6
7        8/19/2012    NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
8/19/2012          NOVOZYMES PRESENTATION ACS 2012 Schäfer




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




                                                                                                    8
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




                                                         9
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




Feb 2012: Next generation




    Cellic CTec3
                                               ®


      We can secure your plant’s
          lowest total cost


                                                          10
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




Feb 2012: Next generation




                Cellic CTec3
                                                          ®




                                                              11
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
8/19/2012           NOVOZYMES PRESENTATION ACS 2012 Schäfer


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


                                                                                                                 14
8/19/2012      NOVOZYMES PRESENTATION ACS 2012 Schäfer


…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




                                                                                                                15
8/19/2012      NOVOZYMES PRESENTATION ACS 2012 Schäfer




…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/
                                                                                                                     16
8/19/2012          NOVOZYMES PRESENTATION ACS 2012 Schäfer



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


                                                                                                   17
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer



3     Production of Renewable Chemicals
      – a Good Fit to our Technology and our Vision




                                                             Yeast         Bio-
                                                          Fermentation   ethanol

                                     Fermentable
                                        sugars




                                                                                   18
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer



3   Production of Renewable Chemicals
    – a Good Fit to our Technology and our Vision




                                                             Yeast         Bio-    Renewable
                                                          Fermentation   ethanol   chemicals
                                     Fermentable
                                        sugars




                                                                                          19
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer



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




                                                                                            20
8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer



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

                                                                                            21
22   8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
23   8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
24      8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




Novozymes/Cargill partner with BASF

      August 18th, 2012
      Cargill & Novozymes started in 2008
      BASF joins the cooperation now
25     8/19/2012       NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
26    8/19/2012    NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
27                        8/19/2012        NOVOZYMES PRESENTATION ACS 2012 Schäfer




     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

                                                                                                                                                                                  27
28      8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




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
29            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.
                                                     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
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
31         8/19/2012          NOVOZYMES PRESENTATION ACS 2012 Schäfer



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
8/19/2012    NOVOZYMES PRESENTATION ACS 2012 Schäfer




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




                                                                                  32
33   8/19/2012   NOVOZYMES PRESENTATION ACS 2012 Schäfer




     Thank you!




                                                           tsch@novozymes.com

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Biological Solutions in a chemical world

  • 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 2
  • 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 3
  • 4. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 6. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 6
  • 7. 7 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 8. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 8
  • 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 9
  • 10. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer Feb 2012: Next generation Cellic CTec3 ® We can secure your plant’s lowest total cost 10
  • 11. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer Feb 2012: Next generation Cellic CTec3 ® 11
  • 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
  • 13. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 14
  • 14. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer …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 15
  • 15. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer …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/ 16
  • 16. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 17
  • 17. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 3 Production of Renewable Chemicals – a Good Fit to our Technology and our Vision Yeast Bio- Fermentation ethanol Fermentable sugars 18
  • 18. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 3 Production of Renewable Chemicals – a Good Fit to our Technology and our Vision Yeast Bio- Renewable Fermentation ethanol chemicals Fermentable sugars 19
  • 19. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 20
  • 20. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 21
  • 21. 22 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 22. 23 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 23. 24 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer Novozymes/Cargill partner with BASF  August 18th, 2012  Cargill & Novozymes started in 2008  BASF joins the cooperation now
  • 24. 25 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 25. 26 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 26. 27 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 27
  • 27. 28 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 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. 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
  • 30. 31 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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
  • 31. 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer 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 32
  • 32. 33 8/19/2012 NOVOZYMES PRESENTATION ACS 2012 Schäfer Thank you! tsch@novozymes.com