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Industrial Biotechnology: on the
  Road to Sustainable Biorefineries
  for Biochemical and Biofuels
  Production


Richard J. LaDuca
  April 28, 2010


Nordic Green II
 Conference

   Palo Alto, CA
Genencor at a Glance….

We put Biotechnology to work… developing &                              Industrial
producing enzymes for industrial applications.                          Enzymes
                                                                     Animal Feed Enzymes
                                                                      Cellulosic Enzymes
   History traced to 1982                                               Food Enzymes
                                                                      Fabric & Household
   May 2005: Division of Danisco                                             Care
                                                                       Grain Processing
   Industrial Biotechnology Focus                                      Textiles Enzymes


   Over 250 commercial products
                                                                     Biochemicals
   Proven innovator: ~3,500+                                                Lysine
   owned & licensed patents and                                           Threonine
                                                                         Tryptophan
   patent applications                           1,3 Propanediol
                                                                            Indigo
                                                   H                        Biotin
   > $800 MM USD annual turnover                       C   C
                                                               CH3
                                                                        Ascorbic Acid
                                                                       1,3 Propanediol
   ~ 1,500 employees worldwide                   H2C           CH2
                                                                        BioIsoprene™
                                                  BioIsoprene™

                                                                                           2
Genencor® business timeline
A Leader in Industrial Biotechnology

                                                                               Danisco acquires GCOR, 100%

                         Eastman Chemical 1993,           Danisco
                                  50%                    1999, 50%



Dual Kodak-Cultor ownership that
            forms:
   Genencor International, Inc.         GCOR buys Gist- Brocades Enzymes (Brugge,                New Wuxi China plant and
                                                           BE)                                    application laboratories

  Genentech & Corning                     GCOR buys Solvay Enzyme             (USA,
                                                 Argentina, Germany)                                    Shanghai Research Center
   form Genencor, Inc.
                                             GCOR buys Wuxi Enzymes (China)

                                                                                                                      Cedar Rapids
                                          GCOR buys Enzyme Bio-Systems, (USA)                                        expansion and
                                                                                                                    establishment of
                                             GCOR buys Rhodia Enzymes (UK)                                             Grain CoE




1982                         1990          1995   1996   1999   2002   2003              2005    2007        2008      2009



An early pioneer in modern industrial biotechnology
                                                                                                                                       3
Genencor Biotechnology


Our Core Competency:
  We design and operate Cell Factories

   – We rapidly create engineered proteins that accomplish the previously
     impossible and deliver significant value to our most important
     customers.

   – We engineer the metabolic pathways of micro-organisms to produce
     enzymes, proteins, and other bio-molecules at industrial scale and
     economics.




                                                                            4
Industry Trends: Fuels / Chemicals

   Petroleum-based Processes                             Biobased Processes
Existing, mature refining infrastructure;        Building off of early successes using
                                                 starch-based feedstocks
high efficiencies, low cost
                                                 Enables a $5-10 billion dollar industry
Enables a $2+ trillion dollar chemical           Driven by a renewable raw material
industry worldwide                               base
Volatility in oil price leads to volatility in   Innovation and advances in enzyme
chemical / fuel prices                           processing efficiencies and costs
Feedstock source is non-renewable                Trend towards: less GHG emissions;
                                                 less non-renewable energy usage; and
Innovation potential around existing             reduced environmental impact
chemical processes has been played               Move to waste biomass as a feed
out                                              source
GHG / CO2 abatement concerns                     Technology innovation and systems
                                                 integration drive move to
                                                 BIOREFINERIES




                                                                                           5
Biorefinery:




    “A biorefinery is a facility that converts waste
    biomass into fuels, power, and chemicals.

    The biorefinery concept is analogous to today's
    petroleum refineries, which produce multiple fuels
    and products from petroleum.”
    - DOE 2008, Biomass Program




                                                         66
Industrial Biotechnology: delivering
technology enabling Biorefineries
   Non-Renewable                        Renewable                       Renewable
    Feedstocks                          Feedstocks                      Feedstocks
          Crude                           Agricultural                        Biomass
           Oil                             Products                           Wastes

      Petro-Refining /                       Bio                             Bio
         Cracking                          Refining      Biorefineries Refining
                                                                           using
                                 E                                   E
                                                         renewable raw
       Fractionation         Starch
                           Processing
                                         Fractionation   materials as
                                                              Cellulose
                                                             Processing
                                                                        Fractionation
                            Enzymes
                                                         feedstocks are TODAY
                                                              Enzymes

      Chem Building                      Starch C5/C6
         Blocks
                                                         delivering products
                                                                        C5/C6 Sugars,
                                            Sugars                         Lignin
                                                         that compete with
       Chem Syn. &                           Bio                             Bio
       Conversion                E        Conversion
                                                         petroleum refining
                                                                     E Conversion
                            Metabolic                          Metabolic
                            Pathway                            Pathway
       Petro-based         Engineering     Biobased                           Biobased
                                                              Engineering
        Products                           Products                           Products


 Chemicals        Fuels       Biochemicals Biofuels              Biochemicals Biofuels

    Not Sustainable                      Sustainable                        Sustainable
    Proven Method                    Proven Method                     In Development
     Price Volatility                    Food Based                         Ag Wastes
 Existing Infrastructure       Existing Infrastructure          No Existing Infrastructure
                                                                                          7
Genencor’s Road to Sustainable
BIOREFINERIES



 Enzymes for starch processing
 1st Generation Biochemicals & Bioethanol
 2nd Generation Bioethanol
 Renewable Biochemicals and Biofuels




                                            98
Conventional 1st generation ethanol
 production process

                               Thermo-stable      E                                               Alcohol
                               alpha amylase            Glucoamylase          Yeast              recovery


  Milo                           Liquefaction           Saccharification                     Distillation &
                                                                           Fermentation
 Corn                                                                                        dehydration
 Wheat        Water
  Rye                            JET COOKER


                  *
 Barley                            >100° C
Tapioca                            5–8 MIN
                                                                                                    STORAGE
                                                                                                      TANK



                                                               60° C
                                                             8–10 HRS
                                                             (optional)

GRINDING           SLURRY
                    TANK


                                          SECONDARY
                                         LIQUEFACTION
                                             95° C


                                                          *
                                            ~90 MIN




                                                                                          DDGS


     pH adjustment steps are not shown
                                                                                                              9
No-cook ethanol production process


                                                                         Alcohol
                                                                        recovery
   Milo
  Corn
  Wheat                                   Saccharification &          Distillation &
   Rye                                      fermentation              dehydration
                 Water
  Barley
 Tapioca

                                                                         STORAGE
                                                                           TANK




                     SLURRY
 GRINDING             TANK




                                      *
STARGEN™
     &
   Yeast
                                                               DDGS


    E
  pH adjustment steps are not shown                                                    10
Genencor & DuPont: 1st Generation
Biochemicals from Renewable Raw
Materials




                      E




                                    11
1st Generation Biochemicals




          Genencor’s enzyme technology is at the heart of the
           integrated bioprocess to produce 1,3 propanediol

                                                                12
Enzyme Activities Important
  in Biomass Hydrolysis


Accellerase® DUET achieves 3-     Many customers and pilot
fold dose reduction on multiple   facilities are trialing Accellerase®
substrates
                                  Genencor® is actively working
Accellerase® DUET enabling        on future generations of
commercialization with $0.50      Accellerase® products.
enzyme cost / Gal EtOH
          E




                                                                     13
Total Sugar Conversion: Pretreated
Hardwood Pulp, 3 day Saccharification



                                           E




         0.17 mL Accellerase® DUET vs. 1.0 mL Accellerase® 1500 (5.9X)


                                                                         14
2nd Generation Advanced Biofuels


 50/50 Joint Venture between Danisco and DuPont
 Commercializing integrated technology to produce cellulosic ethanol
 Over $140mm investment over 3 years
 Biomass feedstock-flexible (utilizing cob and switchgrass in Eastern Tennessee)
 pilot plant 2010
 Commercial plant in 2012




                                                           E




                                                                                   15
Isoprene Production:



                   PETROLEUM             CHEMICAL               BIOBASED
     TREES
                    CRACKING             SYNTHESIS              PROCESS




• Slow           • Extractive          • High cost           • Renewable
                   distillation from                           feedstocks
• Not              Ethylene &          • Petroleum
  commercially     Propylene             feedstocks          • Biochemical
  relevant         production                                  AND Biofuel
                                       • Mfg.                  Products
                 • Price linked to       infrastructure in
                   oil prices            Russia & Japan
                 • Moving to
                   “light” streams                                           16
The Vision: Isoprene from Biomass


   Biomass
                                  Sugars
                                      OH
                                                    Isoprene
                                       O
                           HO
                             HO
  Corn       Switchgrass               OH     OH


                                  D-Glucose
                                                   2-Methyl-1,3-butadiene
                                   +
                            other C5 and C6
                                sugars
Sugar cane      Woody
 Molasses      biomass


 We aim to develop an efficient and sustainable fermentation
      route to isoprene from carbohydrate feedstocks
                                                                            17
Genencor and Goodyear leveraging
each others’ expertise …




                                                                            H            CH3

                 E                      E                                        C   C

                                                                           H2C           CH2



                                                           BioIsoprene™
                                                                           Polymer-Grade
   Renewable         Microbial Strain        Large Scale    recovery &
                                                                            BioIsoprene™
  Feedstock(s)        Development           Fermentation    purification
                                                                               Product
                                                             knowhow




   Integrated biobased process for production of BioIsoprene™


                                                                                               18
C5 Platform Progress – Stage I Biochemicals
           BioIsoprene™ Technology




                        Conceptual View of Cell Factory
Glucose
                    C6 ►3C           DXP Pathway
Sucrose /           (C5)
Biomass                                             Isoprene   Isoprene
                    3C ►2C                Cells     Synthase   Recovery
Glycerol
                   16C ►2C          MVA Pathway
                                                     E
Plant Oils



   Multiple feedstocks possible
   Two feeder pathways to isoprene precursor
   Isoprene synthase
   Gas Phase recovery
                                                                          19
BioIsoprene™ BioRefinery:


                                                                                      Market
                                                                                    Applications
                                         Polymer Grade        Cis 1,4
                                                                                        Tires /
                                         BioIsoprene™      Polyisoprene
                                                                                     Elastomers
                                            Product      Synthetic Rubber

                                                                                   Replace Natural
                                                                                      Rubber
Renewable          Gas-phase
Feedstocks       BioIsoprene™                                                     Synthetics in tires
               product recovered
               & purified to liquid-
                      phase
                                                                   rDNA Host      Non-tire synthetics
                  BioIsoprene™
                   produced in                                     Systems:
                    gas-phase                                      E.coli; Yeast; Fungi;
                                                                                      Adhesive
      E          • in-situ                                         others            Applications
                   purification
                 • relieves end
                   product
                   inhibition/toxicity
                                                                                    Other styrene
                                                                                     adhesives
                 • faster, better,
                   cheaper



                                                                                                        20
BioIsoprene™ Molecule:
        Genencor’s Unique C5 Platform
                                                                                                                           Tires




                                Biochemicals
                                                             Purification
                                                                                                                      Adhesives

                                                                                         High Purity
                                                                                   BioIsoprene™ monomer

                                                                                                               Specialty Polymers
                                                            H                CH3

                                                                 C     C

                                                           H2C               CH2



                                                             Isoprene
                                                             Monomer                                                Gasoline
Renewable    Microbial Strain    Large Scale   Gas Phase
                                                                                                 C10 Isomers
Feedstocks    Development       Fermentation   Recovery



                                                                                   C15 Isomers
                                                                                                     +


                                                                                     + Other Fuels & Blends
                                                                                                                           Diesel

                                      Biofuels                                      BioIsoFuel™ Examples                 Jet Fuel
                                                                 Chemical
                                                                 Catalysis

                                                                                                                               21
C5 Platform Progress – Stage I
Biochemicals
                                                                                                                     Tires




          BioIsoprene™ Project
                                                                Purification
                                                                                                                Adhesives

                                                                                        High Purity
                                                                                  BioIsoprene™ monomer

                                                                                                         Specialty Polymers
                                                               H            CH3

                                                                    C   C

                                                              H2C           CH2



                                                                Isoprene
                                                                Monomer
                Microbial Strain    Large Scale   Gas Phase
 Sugar
                 Development       Fermentation   Recovery




         In Stage I development we have started from sugar

                                                                                                                         22
C5 Platform Progress – Stage II Biofuels
         BioIsoFuel™ Products

         Concerted effort converting biomass to sugar
              • Leverage long history / IP with biomass enzymes


                           Continued optimization
                                                                     Hybrid biological + chemical process

                                                                       H                CH3

                                                                            C     C

                                                                      H2C               CH2



                                                                        Isoprene
                                                                        Monomer                                           Gasoline
 Renewable             Microbial Strain    Large Scale   Gas Phase
                                                                                                            C10 Isomers
 Feedstocks             Development       Fermentation   Recovery



                                                                                              C15 Isomers
                                                                                                                +


                                                                                                + Other Fuels & Blends
                                                                                                                               Diesel


                                                                                              BioIsoFuel™ Exaamples           Jet Fuel
                                                                            Chemical
                                                     Partner                Catalysis

                                                                                                                                     23
Genencor®: on the Road to
Sustainable Biorefineries

The biobased economy is here and its growing
• ~5-10% of chemicals will be bio-based by 2012
  (McKinsey 2006)
High oil prices and environmental concerns are key
factors fueling the biobased economy
Innovations in enzyme processing are enabling the
development of sustainable integrated systems for
biomass processing to fermentable sugars
New business models / Strategic relationships and
Technology Integrators will speed Biorefinery
development
Biobased processes will continue to deliver Strategic
alternatives to petrochemicals




                                                        24
Our Vision of the Biobased Economy


  We envision a future where biotechnology
  fulfills many unmet needs…
      In development and deployment of
        industrial enzymes
      In the production of fuels, chemicals and
        materials

  We envision a future where biotechnology
  helps create sustainable industrial
  activities

  We envision a future where biorefineries
  take their place alongside oil refineries

  We aspire to be recognized as a leader in
  world-changing technology solutions.

                                                   25
Questions:




             26

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  • 1. Industrial Biotechnology: on the Road to Sustainable Biorefineries for Biochemical and Biofuels Production Richard J. LaDuca April 28, 2010 Nordic Green II Conference Palo Alto, CA
  • 2. Genencor at a Glance…. We put Biotechnology to work… developing & Industrial producing enzymes for industrial applications. Enzymes Animal Feed Enzymes Cellulosic Enzymes History traced to 1982 Food Enzymes Fabric & Household May 2005: Division of Danisco Care Grain Processing Industrial Biotechnology Focus Textiles Enzymes Over 250 commercial products Biochemicals Proven innovator: ~3,500+ Lysine owned & licensed patents and Threonine Tryptophan patent applications 1,3 Propanediol Indigo H Biotin > $800 MM USD annual turnover C C CH3 Ascorbic Acid 1,3 Propanediol ~ 1,500 employees worldwide H2C CH2 BioIsoprene™ BioIsoprene™ 2
  • 3. Genencor® business timeline A Leader in Industrial Biotechnology Danisco acquires GCOR, 100% Eastman Chemical 1993, Danisco 50% 1999, 50% Dual Kodak-Cultor ownership that forms: Genencor International, Inc. GCOR buys Gist- Brocades Enzymes (Brugge, New Wuxi China plant and BE) application laboratories Genentech & Corning GCOR buys Solvay Enzyme (USA, Argentina, Germany) Shanghai Research Center form Genencor, Inc. GCOR buys Wuxi Enzymes (China) Cedar Rapids GCOR buys Enzyme Bio-Systems, (USA) expansion and establishment of GCOR buys Rhodia Enzymes (UK) Grain CoE 1982 1990 1995 1996 1999 2002 2003 2005 2007 2008 2009 An early pioneer in modern industrial biotechnology 3
  • 4. Genencor Biotechnology Our Core Competency: We design and operate Cell Factories – We rapidly create engineered proteins that accomplish the previously impossible and deliver significant value to our most important customers. – We engineer the metabolic pathways of micro-organisms to produce enzymes, proteins, and other bio-molecules at industrial scale and economics. 4
  • 5. Industry Trends: Fuels / Chemicals Petroleum-based Processes Biobased Processes Existing, mature refining infrastructure; Building off of early successes using starch-based feedstocks high efficiencies, low cost Enables a $5-10 billion dollar industry Enables a $2+ trillion dollar chemical Driven by a renewable raw material industry worldwide base Volatility in oil price leads to volatility in Innovation and advances in enzyme chemical / fuel prices processing efficiencies and costs Feedstock source is non-renewable Trend towards: less GHG emissions; less non-renewable energy usage; and Innovation potential around existing reduced environmental impact chemical processes has been played Move to waste biomass as a feed out source GHG / CO2 abatement concerns Technology innovation and systems integration drive move to BIOREFINERIES 5
  • 6. Biorefinery: “A biorefinery is a facility that converts waste biomass into fuels, power, and chemicals. The biorefinery concept is analogous to today's petroleum refineries, which produce multiple fuels and products from petroleum.” - DOE 2008, Biomass Program 66
  • 7. Industrial Biotechnology: delivering technology enabling Biorefineries Non-Renewable Renewable Renewable Feedstocks Feedstocks Feedstocks Crude Agricultural Biomass Oil Products Wastes Petro-Refining / Bio Bio Cracking Refining Biorefineries Refining using E E renewable raw Fractionation Starch Processing Fractionation materials as Cellulose Processing Fractionation Enzymes feedstocks are TODAY Enzymes Chem Building Starch C5/C6 Blocks delivering products C5/C6 Sugars, Sugars Lignin that compete with Chem Syn. & Bio Bio Conversion E Conversion petroleum refining E Conversion Metabolic Metabolic Pathway Pathway Petro-based Engineering Biobased Biobased Engineering Products Products Products Chemicals Fuels Biochemicals Biofuels Biochemicals Biofuels Not Sustainable Sustainable Sustainable Proven Method Proven Method In Development Price Volatility Food Based Ag Wastes Existing Infrastructure Existing Infrastructure No Existing Infrastructure 7
  • 8. Genencor’s Road to Sustainable BIOREFINERIES Enzymes for starch processing 1st Generation Biochemicals & Bioethanol 2nd Generation Bioethanol Renewable Biochemicals and Biofuels 98
  • 9. Conventional 1st generation ethanol production process Thermo-stable E Alcohol alpha amylase Glucoamylase Yeast recovery Milo Liquefaction Saccharification Distillation & Fermentation Corn dehydration Wheat Water Rye JET COOKER * Barley >100° C Tapioca 5–8 MIN STORAGE TANK 60° C 8–10 HRS (optional) GRINDING SLURRY TANK SECONDARY LIQUEFACTION 95° C * ~90 MIN DDGS pH adjustment steps are not shown 9
  • 10. No-cook ethanol production process Alcohol recovery Milo Corn Wheat Saccharification & Distillation & Rye fermentation dehydration Water Barley Tapioca STORAGE TANK SLURRY GRINDING TANK * STARGEN™ & Yeast DDGS E pH adjustment steps are not shown 10
  • 11. Genencor & DuPont: 1st Generation Biochemicals from Renewable Raw Materials E 11
  • 12. 1st Generation Biochemicals Genencor’s enzyme technology is at the heart of the integrated bioprocess to produce 1,3 propanediol 12
  • 13. Enzyme Activities Important in Biomass Hydrolysis Accellerase® DUET achieves 3- Many customers and pilot fold dose reduction on multiple facilities are trialing Accellerase® substrates Genencor® is actively working Accellerase® DUET enabling on future generations of commercialization with $0.50 Accellerase® products. enzyme cost / Gal EtOH E 13
  • 14. Total Sugar Conversion: Pretreated Hardwood Pulp, 3 day Saccharification E 0.17 mL Accellerase® DUET vs. 1.0 mL Accellerase® 1500 (5.9X) 14
  • 15. 2nd Generation Advanced Biofuels 50/50 Joint Venture between Danisco and DuPont Commercializing integrated technology to produce cellulosic ethanol Over $140mm investment over 3 years Biomass feedstock-flexible (utilizing cob and switchgrass in Eastern Tennessee) pilot plant 2010 Commercial plant in 2012 E 15
  • 16. Isoprene Production: PETROLEUM CHEMICAL BIOBASED TREES CRACKING SYNTHESIS PROCESS • Slow • Extractive • High cost • Renewable distillation from feedstocks • Not Ethylene & • Petroleum commercially Propylene feedstocks • Biochemical relevant production AND Biofuel • Mfg. Products • Price linked to infrastructure in oil prices Russia & Japan • Moving to “light” streams 16
  • 17. The Vision: Isoprene from Biomass Biomass Sugars OH Isoprene O HO HO Corn Switchgrass OH OH D-Glucose 2-Methyl-1,3-butadiene + other C5 and C6 sugars Sugar cane Woody Molasses biomass We aim to develop an efficient and sustainable fermentation route to isoprene from carbohydrate feedstocks 17
  • 18. Genencor and Goodyear leveraging each others’ expertise … H CH3 E E C C H2C CH2 BioIsoprene™ Polymer-Grade Renewable Microbial Strain Large Scale recovery & BioIsoprene™ Feedstock(s) Development Fermentation purification Product knowhow Integrated biobased process for production of BioIsoprene™ 18
  • 19. C5 Platform Progress – Stage I Biochemicals BioIsoprene™ Technology Conceptual View of Cell Factory Glucose C6 ►3C DXP Pathway Sucrose / (C5) Biomass Isoprene Isoprene 3C ►2C Cells Synthase Recovery Glycerol 16C ►2C MVA Pathway E Plant Oils Multiple feedstocks possible Two feeder pathways to isoprene precursor Isoprene synthase Gas Phase recovery 19
  • 20. BioIsoprene™ BioRefinery: Market Applications Polymer Grade Cis 1,4 Tires / BioIsoprene™ Polyisoprene Elastomers Product Synthetic Rubber Replace Natural Rubber Renewable Gas-phase Feedstocks BioIsoprene™ Synthetics in tires product recovered & purified to liquid- phase rDNA Host Non-tire synthetics BioIsoprene™ produced in Systems: gas-phase E.coli; Yeast; Fungi; Adhesive E • in-situ others Applications purification • relieves end product inhibition/toxicity Other styrene adhesives • faster, better, cheaper 20
  • 21. BioIsoprene™ Molecule: Genencor’s Unique C5 Platform Tires Biochemicals Purification Adhesives High Purity BioIsoprene™ monomer Specialty Polymers H CH3 C C H2C CH2 Isoprene Monomer Gasoline Renewable Microbial Strain Large Scale Gas Phase C10 Isomers Feedstocks Development Fermentation Recovery C15 Isomers + + Other Fuels & Blends Diesel Biofuels BioIsoFuel™ Examples Jet Fuel Chemical Catalysis 21
  • 22. C5 Platform Progress – Stage I Biochemicals Tires BioIsoprene™ Project Purification Adhesives High Purity BioIsoprene™ monomer Specialty Polymers H CH3 C C H2C CH2 Isoprene Monomer Microbial Strain Large Scale Gas Phase Sugar Development Fermentation Recovery In Stage I development we have started from sugar 22
  • 23. C5 Platform Progress – Stage II Biofuels BioIsoFuel™ Products Concerted effort converting biomass to sugar • Leverage long history / IP with biomass enzymes Continued optimization Hybrid biological + chemical process H CH3 C C H2C CH2 Isoprene Monomer Gasoline Renewable Microbial Strain Large Scale Gas Phase C10 Isomers Feedstocks Development Fermentation Recovery C15 Isomers + + Other Fuels & Blends Diesel BioIsoFuel™ Exaamples Jet Fuel Chemical Partner Catalysis 23
  • 24. Genencor®: on the Road to Sustainable Biorefineries The biobased economy is here and its growing • ~5-10% of chemicals will be bio-based by 2012 (McKinsey 2006) High oil prices and environmental concerns are key factors fueling the biobased economy Innovations in enzyme processing are enabling the development of sustainable integrated systems for biomass processing to fermentable sugars New business models / Strategic relationships and Technology Integrators will speed Biorefinery development Biobased processes will continue to deliver Strategic alternatives to petrochemicals 24
  • 25. Our Vision of the Biobased Economy We envision a future where biotechnology fulfills many unmet needs…  In development and deployment of industrial enzymes  In the production of fuels, chemicals and materials We envision a future where biotechnology helps create sustainable industrial activities We envision a future where biorefineries take their place alongside oil refineries We aspire to be recognized as a leader in world-changing technology solutions. 25