Generating Customer Value with Renewable Chemicals: The Case for Fermentation Collaboration

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Moris French
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1 Generating Customer Value with Renewable Chemicals: The Case for Fermentation Collaboration Christopher J. Guske, Ph.D. D 2 Biotech Consulting, LLC BIOWC17

Research Fellow, Tate & Lyle, and VP, Engineering, DTL Nearly 30 yrs of Biotech experience (CP Kelco, NutraSweet, Tate & Lyle) Fermentation

2 The Next New Adventure Christopher J. Guske, Ph.D. D 2 Biotech Consulting, LLC Dennis Adkesson Independent Consultant Associate Former Director, BioVentures and Support Services, Tate & Lyle Research Fellow, Tate & Lyle, and VP, Engineering, DTL Nearly 30 yrs of Biotech experience (CP Kelco, NutraSweet, Tate & Lyle) Fermentation subject-matter expert Downstream conversant Process R&D expertise Over 50 yrs corn wet mill experience (Tate & Lyle) Over 20 yrs of Biotech experience Downstream subject-matter expert Fermentation conversant Engineering expertise

3 Key Industry Milestones Interfaced with/assessed ~100 biotech opportunities/companies. 1,3-propanediol (PDO; DuPont Tate & Lyle BioProducts): Process development (multiple strain generations, scale-down experiments, media optimization, etc.), pilot plant scale up (fermentation and downstream), plant design, and Loudon, TN, plant startup support. Fermentation scaled from 13kL to 600kL, hitting 95% of pilot performance at startup and exceeding thereafter. Achievement widely recognized as the Gold Standard in Industrial Biotechnology; received the 2007 American Chemical Association s Heroes of Chemistry Award. 1,4-butanediol (BDO; Genomatica): Produced 5Mlb of BDO at 600kL scale (DTL BioProducts PDO facility) after 14 months of lab and pilot plant work, including several strain generations and upstream and downstream process optimization; process was recipient of 42nd Kirkpatrick Chemical Engineering Achievement Award. Farnesene (Amyris): Contract manufacturing in Decatur, IL; process optimization reduced production costs 2-3x; process received a 2014 Presidential Green Chemistry Challenge Award. Polyhydroxyalkanoate (PHA; DaniMer Scientific): Technical demonstration and scale up of strains. Astaxanthin (Igene JV): Small-scale lab and on-site plant support resulted in a 650% titer and productivity increase, resolving issues of scale-up in a converted citric acid plant.

4 D 2 Biotech Consulting, LLC/Adkesson Experience Process conceptualization and economic evaluation for both operating and capital costs. Small-scale development (10L) through large scale (600 m3) production fermentation experience, including mechanically agitated and bubble column bioreactors and diverse operating rheologies (low to high viscosity, Newtonian and Non-Newtonian). Process development, technical transfer, troubleshooting, process analysis, experimental design and applied statistics, tracking and optimization, cost reduction, downstream recovery, bioreactor design, plant startups, strain evaluation, media development and optimization, and scale up/scale down experience. Experience with diverse products, processes, and organisms. Broad knowledge of downstream unit operations. New product development at pilot scale. Project management for both R&D and plant capital projects ( $100MM) Broad knowledge of corn wet milling industry

5 Green Chemistries Dominated by Fermentation Microbes are amazing entities: Small, self-replicating, self-healing, chemical factories Simultaneous, complex chemistries under mild operating conditions Can be easily retooled Diversity of products from the same hardware footprint Low carbon footprint relative to petrochemical routes Potential exceptions: Inorganic catalysis to perform backbone modifications (e.g., Rennovia) Reactions requiring extreme temperatures or pressures, or toxic chemicals Post-fermentation chemical modifications Enzymatic conversions

6 Fermentation Processes are Highly Diverse Diversity of organisms: E. coli S. cerevisae Phaffia Aspergillus PPFMs Pichia Yarrowia Cyanobacteria Actinomycetes Algae Methanotrophs CB1 Diversity of operating conditions: ph Temperature Dissolved oxygen Media comp. Batch Fed-batch Continuous Asepsis Agitation Aeration Sterilization Contamination Key points: Fermentation is part art and part science A lot of things need to go right to have a good outcome. All it takes is for one thing to go wrong and all the things done right get flushed down the drain.

7 Fermentation Processes are Highly Diverse Diversity of recovery/purification processes: What is the strategy? Intracellular Extracellular Gas Liquid Solid Background matrix Coproducts/ contaminants Purity What technologies are required? Filtration IX Carbon Centrifugation Evaporation Crystallization Distillation Chromatography Solvent extraction Electrodialysis

8 Fermentation Processes are Highly Diverse Diversity of Feedstocks: Glucose Fructose Sucrose C5/C6 Starch Glycerol Vegetable oils Molasses CSL Organic acids Alcohols Industrial gases Feedstock factors to consider: Geography: sourcing, transportation, co-location, etc. Price volatility Purity: Impact on downstream? Cheap/unrefined: Are you taking out someone else s trash? Cost-yield relationship

9 Product vs. Process Customer needs drive green chemistry products: Greener Smaller carbon footprint Take the (inefficient) animal out of the process Better for the environment/environmentally friendly/better specificity Petrochemical replacement Green products are identified then the question is how to produce them in an economically and commercially viable way? If scale up was easy, everyone would be doing it.

10 Fermentation Process Development It is very rare that any one company can do it all: Nothing is textbook. Nothing is as easy as you think it is. You don t know what you don t know. There will be snakes in the grass. The key: Know your strengths and weaknesses and collaborate with those who know Who has the missing expertise? Where can speed to market be gained? Who has the hardware/capital to implement? Who has an established track record of success?

Wet Milling: experience processing and separating biological materials at large,

11 Successful Collaborations Genencor, DuPont and Tate & Lyle: 1,3-propanediol Genencor/DuPont strain collaboration Fermentation beauty contest 100 Years of Corn Wet Milling: experience processing and separating biological materials at large, economic scale Plant construction experience Feedstock backwards integration and co-location

12 Successful Collaborations Genencor, DuPont and Tate & Lyle: 1,3-propanediol (cont.) A fully integrated development process Successful piloting Successful commercial launch

13 Successful Collaborations Genomatica and Tate & Lyle: 1,4-butanediol 14 month piloting: process very similar to 1,3-propanediol E. coli Similar unit operations 5 million pounds produced in one month at DTL BioProducts commercial facility

Successful Collaborations Igene and Tate &

tolling at large scale with another company

process to its UK-based citric plant Scale up

fermentors identified and resolved issues

14 Successful Collaborations Igene and Tate & Lyle: Astaxanthin Igene had previously been tolling at large scale with another company Tate & Lyle tech transferred/adapted the process to its UK-based citric plant Scale up did not work as planned On-site parallel lab fermentors identified and resolved issues Final plant performance exceeded previous lab fermentor performance

15 Future Successful Collaborations? Industry has become highly specialized: no one does it all, per se

16 Thank you for your attention! Christopher J. Guske, Ph.D. D 2 Biotech Consulting, LLC c.guske@comcast.net (217)

Susterra Propanediol Heat Transfer Fluids

Susterra Propanediol Heat Transfer Fluids March 11, 2016 Who is DuPont Tate & Lyle? DTL is a joint venture formed in 2004 between DuPont and Tate & Lyle to produce 1,3 propanediol (PDO) from corn starch,