Transforming Industries With High Performance Enzymes. David P. Weiner, Ph.D. December 10, 2013
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1 Transforming Industries With High Performance Enzymes David P. Weiner, Ph.D. December 10, 2013
2
3 Global Challenges & Opportunities Global Population (millions) Unprecedented challenges to planet s resources and environment Energy, Food, Water, Chemicals & Materials, Climate Opportunity for biotechnology to contribute sustainable solutions Current World Population:
4 The Power of Enzymes High catalytic efficiencies Exquisite selectivity enantio-, chemo-, regio- Direct access to products Environmentally friendly Natural, biodegradable Reduce or eliminate waste streams Evolvable
5 Enzymes Products in Our Daily Lives Detergents & cleaners Industrial Human Nutrition Pharmaceutical Personal care Animal health & nutrition Ethanol & other biofuels
6 Enzyme Discovery at Verenium Faster, Comprehensive, Captures Nature s Diversity TRADITIONAL APPROACH Culture Microbes VERENIUM S APPROACH Extract Microbial DNA Clone Construct edna Library Screen Typical culturing methods access <0.1% of biodiversity High Throughput Screens Verenium s Direct Approach Bypasses Need for Culturing
7 Unprecedented Microbial Biodiversity Over 2000 edna libraries Encompass the genomes from over 1 million organisms Billions of genes, billions of potential new enzymes
8 Verenium s Unique Suite of Technologies Provides Powerful Competitive Advantage Enzyme Discovery Ultra-high Throughput Screening DirectEvolution Technologies Applications Expression, Scale-up & Manufacturing
9 From the Deep Blue to the Anthropogenic Abyss 2013 Verenium Corporation
10 Development of Pyrolase Cellulase Capturing The Best From Nature Screened Verenium s extensive environmental DNA libraries Discovered multiple candidates Applications work identified ideal enzyme for fracturing Scaled-up & commercialized as Pyrolase cellulase
11 Development of Pyrolase HT Cellulase Improving The Best From Nature (~85 o C) (~110 o C) Increased temperature range and ph while maintaining unique performance properties of parent enzyme
12 Development of a Novel Alpha-Amylase for Starch Liquefaction HIGH TEMP, LOW ph α-amylase glucoamylase Higher activity Opportunity Higher for new enzyme temp optimum Lower ph optimum Unmet Need
13 PERFORMANCE 2013 Verenium Corporation Discovery of Amylase Lead Enzymes PERFORMANCE THRESHOLD ph, Temp, Activity 3 lead enzymes Guaymas Basin 15 enzymes Mediterranean Sea Millions of potential enzymes Deep Pacific ENVIRONMENTAL SAMPLES INITIAL SCREEN SECONDARY SCREEN
14 Verenium s GeneReassembly SM Strategy 3 parental genes (enzymes) DIVERSIFY Low ph activity, high specific activity and expression BLEND 9 segments synthesized for each gene (8 points of demarcation) 3 9 combinations = 19,683 daughter constructs HIGH THROUGHPUT SCREEN Best gene selected
15 Fuelzyme Alpha-Amylase is Differentiated from the Competition by Nature Itself From a Different Branch on the Phylogenetic Tree of Life Different Mode of Action Produces More Uniform Substrate Most α-amylases Fuelzyme alpha-amylase Superior thermostability, broader ph range & unique mode of action
16 Verenium Esterases & Lipases Over 600 unique esterases & lipases discovered Wide variety of useful properties including: Diverse fatty acid selectivities Broad range of temperature and phs Activity on wide range of substrates Key: Verenium lipases Commercial lipases
17 2013 David P. Weiner 17
18 Photo courtesy of Prof. Greg Rouse, SIO
19 Development of Enzymatic Process for Healthier Edible Oils + Selectively remove unwanted fatty acid Upgrade heath profile, upgrade value Alternative to plant breeding / transgenics
20 Verenium Corporation Discovery of a Highly Selective Lipase 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% FA #5 FA #4 FA #3 FA #2 FA #1 Unprecedented range of enzyme selectivities from Nature GC screen identified enzyme with selectivity to FA #4 Provided starting point for further optimization
21 Optimization of Lipase Selectivity Evolving the Best from Nature Wild type No Enzyme Constructed GSSM SM Library (~400 residues) Wild Type UHTP Screen (100,000 clones) Evolved UHTP Screen (All possible combinations) Exquisite selectivity achieved (>99%) Additional round of evolution enhanced thermostability Evolved Variants Exceeded all performance targets 21
22 2013 Verenium Corporation Industrial Enzymes: Profitable, Growing Markets Today, New Markets Emerging New Enzyme Markets Source: Market size estimates based on Verenium internal estimates and L. Hepner & Associates Industrial Enzymes Report published in March 2013.
23 Verenium s Enzyme Collection 4,000+ Unique Proprietary Enzymes For Future Products Amidases (primary) Amidases (secondary) Dehalogenases Epoxide hydrolases Esterases Lipases Phospholipases Alphafucosidases Alphagalactosidases Alphaglucoronidases Amylases Arabinofuranosidases Betaglucosidases Betamannosidases Cellobiohydrolases Cellulases Fucosidases Galactanases Glucanases Mannanases Pectinases Pullulanases Xylanases Nitrilases Phosphatases Proteases Isomerases Aldolases Ammonia-lyases Ammonia-lyases (Tryptophanases) C-O-lyases C-O-lyases (Pectate lyases) Dehydratases Miscellaneous lyases Catalases Dehydrogenases Oxidases Transaminases Nature does not hurry, yet everything is accomplished -- Lao Tsu, 600BC
24 Looking Ahead to 2050 Strong foundation of technologies linked to business strategy Enzymes will be a key driver of the growing biobased economy Discovery together with evolution is expanding the role of enzymes
25 Acknowledgements The Verenium team past & present Our academic collaborators Our industrial partners & customers Dedicated to the memory of Patti Kretz and Patrick McCroskey
26 Verenium is Industry, Evolved. Through our unique access to nature s ever-evolving biodiversity, we create eco-friendly enzyme products that improve performance and lower costs for today s global industries 2013 Verenium Corporation
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