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VTT TECHNICAL RESEARCH CENTRE OF FINLAND LTD Creating bioeconomic growth Prof. Dr. Antti Vasara President & CEO, VTT June 2nd, 2016 Finland lives from research and innovation Note: Figures are from 2013 03/06/2016 2 VTT Technical Research Centre of Finland Ltd A leading R&D organisation in Nordic countries We provide expert services for our domestic and international customers and partners, both in private and public sectors TOP 2 VTT is second most active patenting organisation in Finland (2014) 36% of Finnish innovations include VTT expertise We use 4 million hours of brainpower a year to develop new technological solutions Net turnover and other operating income 272 M€ for VTT Group in 2015 Personnel 2,470 (VTT Group 31.12.2015 ) (VTT Group’s turnover 185 M€ in 2015) Unique research and testing infrastructure 3.6.2016 Wide national and international cooperation network 3 Ray Kurzweil: Three technologies that will define our future 1 3 The genetics revolution will allow us to REPROGRAM OUR OWN BIOLOGY The robotics revolution will allow us to CREATE A GREATER THAN HUMAN NON-BIOLOGICAL INTELLIGENCE 2 The nanotechnology revolution will allow us to MANIPULATE MATTER AT THE MOLECULAR AND ATOMIC SCALE Pace is accelerating today’s best tools will help us build even better tools tomorrow. Source: Ray Kurzweil http://www.singularityhub.com/2016/04/19/ray-kurzweil-predicts-three-technologies-will-define-our-future/ 03/06/2016 4 Bioeconomy’s significance for Finland Turnover € 64bn Share of employment 11% Share of exports 26% 03/06/2016 Finland seeks to increase its bioeconomy output to 100 billion euros by 2025 and to create 100,000 new jobs in the process. Bioeconomy combines wood processing, chemistry, energy, construction, technology, food and health. Forest based bioeconomy accounts for two thirds. 5 Combining different technologies together KNOWLEDGE INTENSIVE PRODUCTS AND SERVICES SOLUTIONS FOR NATURAL RESOURCES AND ENVIRONMENT SMART INDUSTRY AND ENERGY SYSTEMS 03/06/2016 6 VTT’s R&D infrastructure – an essential part of the national research infrastructure 03/06/2016 3.6.2016 7 TECHNOLOGY FOR BUSINESS Industrial Biotechnology – an enabler of Bioeconomy Prof. Merja Penttilä 03/06/2016 Living Factories Creating Bioeconomic Growth– Industrial Biotechnology Business Seminar Espoo, Finland 2.6.20161 Living Factories – Synthetic biology for a sustainable bioeconomy 2014-2019 03/06/2016 • • • • VTT Technical Research Centre of Finland, Merja Penttilä Aalto University, Markus Linder University of Turku, Eva-Mari Aro 2 Innomedica, Tanja Dowe CO2 03/06/2016 3 CO2 Biotechnology as an enabler ENZYME MICROBE 03/06/2016 4 Is it a technology? Yes, beer and wine... but don’t they brew by themselves? President Sauli Niinistö congratulates the 2016 winner of the Finnish Millenium Technology Prize, Frances Arnold (CalTech, USA), for her work on directed evolution. 03/06/2016 • Directed evolution of industrial enzymes was already practised in Finland in early 1990’s • Enzyme companies operating in Finland have used directed evolution extensively • Large part of Roal’s enzymes are mutants, e.g. thermostable phytase and cellulases 5 Can it deliver? • Biotechnology is suited for large and small scale • • Production levels can be >> 100 g / liter enzymes >> 150 g/ liter chemicals, with yields of 30-95% • Production can be improved 10-1000-fold (don’t jugde what is achievable based on the capability of natural organisms) Baker’s yeast cell volume ~ 40 µm3 Fermentation tanks can be 1 million m3 03/06/2016 6 Biotechnology can provide many platform chemicals Ethanol Isobutanol nButanol 1,3Propanediol Lactic acid Itaconic acid Succinic acid Acetic acid In production (TRL 8-9) Isobutene Isoprene Farnesene 1,4Butanediol Putrescine Fumaric acid Glutaric acid Isobutyric acid Acetone Styrene Cadaverine Malic acid 4-Hydroxy Butyric acid Butyric Acid nPropanol Phenyl acetic acid Hexamethylenediamine Xylonic acid Adipic acid Xylitol Isopropanol 4-Hydroxy styrene 4-Aminobutyric acic Muconic acid Glucaric acid Sorbitol 1,2,4Butanetriol 4-Hydroxy benzoic acid 5-Aminovaleric acid Galactaric acid Glykolic Acid Monoethylene glycol Terpenoids Phenol 1,3Butadiene Malonic acid Propionic acid LGalactonic acid Polyhydroxy alkanoates Propane Acrylic acid Fatty acids Fatty alcohols Adipic acid Polyhydroxy- 3-Hydroxybutyrate propionic(PHB) acid Piloting (TRL 5-7) Research (TRL 1-4) Feasibility of production has been shown for many new chemicals. The picture does not include specialty chemicals 03/06/2016 and drugs, which also can be produced biotechnologically 7 Production of therapeutic human antibodies with filamentous fungi Spider silk produced by microbes Production of glycolic aciid by yeast and its polymerisation into a bioplastic with good barrier properties Many examples of feasibility of metabolic engineering for chemical and fuels production with microbes, including photosynthetic organisms 2010’s 2000’s 1990’s Production of rare sugars with microbes A yeast that produces lactic acid, enabling a costeffective process for production of PLA Yeast and filamentous fungi that produce sugar acids at low pH from biomass sugars Thermotolerant industrial enzymes Biotechnological production of xylitol Pentose utilising baker’s yeast for bioethanol production from lignocellulosics Efficient hydrolytic enzyme mixtures and their production processes Enzyme-aided bleaching of pulp Engineered antibodies for diagnostic purposes Production of bioactive compounds with Sreptomycetes Production of alkaloids with plant cells Human collagen produced by yeast Improvement of filitration of beer with yeast that produces endoglucacase enzyme that hydrolyses glucan originating from barley A brewer’s yeast that does not produce buttery flavour, and thus the step of secondary fermentation can be omitted in beer production Yeasts that produce amylolytic and cellulolytic enzymes for production of alcohol in a consolidated process New DNA cutting restriction enzymes in production 1980’s Finland has been pioneering in biotechnology The achievements are relevant for today’s Bioeconomy We can now improve through ”synthetic biology” The DBTL cycle of Synthetic Biology DESIGN BUILD Hundreds of engineered strains can be tested in a week LEARN TEST Construction of production strains will become >10-fold faster and cheap 03/06/2016 9 The DBTL cycle of Synthetic Biology DESIGN BUILD Design Construction of production strains Production strains and their parts are designed using computational tools Analysis and decisions Hundreds of engineered strains can be tested in a week LEARN Machine learning algorithms can help the researcher to analyse and understand measured data. 03/06/2016 Synthetic DNA is delivered to the cells using genome editing tools such as CRISPR. TEST Cultivation and measurement Robots are cultivating the strains and carry out measurements. The results are automatically stored in databases. 10 Automated strain engineering Computational recepies for the robot to carry out Build and Test phases Full automation of strain construction and cultivation DESIGN BUILD Design Construction of production strains Production strains and their parts are designed using computational tools Analysis and decisions Hundreds of engineered strains can be tested in a week LEARN Machine learning algorithms can help the researcher to analyse and understand measured data. 03/06/2016 Synthetic DNA is delivered to the cells using genome editing tools such as CRISPR. TEST Cultivation and measurement Robots are cultivating the strains and carry out measurements. The results are automatically stored in databases. 11 Natural synthesis power Evolution power Reaction specificity >> 6000 genes >> 1000 (bio)chemical reactions Vast variety of material structures Natural synthesis power Evolution power Reaction specificity CO2 FEEDSTOCK >> 6000 genes >> 1000 (bio)chemical reactions Vast variety of material structures A single unit operation Mild conditions PRODUCTS Natural synthesis power Evolution power Reaction specificity Heterogenous FEEDSTOCK PRODUCT Growth A single unit operation Mild conditions Natural synthesis power Evolution power Reaction specificity FEEDSTOCK PRODUCTS SYNTHETIC BIOLOGY Design of cell factories based on mathematical cell models Automated construction and high through-put selection of production strains New reactions, new products, more efficient production processes Living Factories Synthetic biology for a sustainable bioeconomy 1. Develop genome engineering and automation technologies that will make design and construction of Living Factories predictable, cheap and fast Lowered barrier for Finnish industry to use biotechnology 2. Establish novel cellular chemistries ”from C1 to Cn” new products for chemical and energy industries that are difficult to make chemically (or biotechnically 3. Create Synthetic Living Factories that are most carbon and energy efficient Sustainable processes for bioeconomy 4. Establish an international and dynamic business-research-education environment based of Synthetic Biology courageous new generation of experts with novel business ideas What are the possibilities and challenges in biotechnology? What is the path forward? How to diversify Finnish bioeconomy? Thank you! 03/06/2016 17 What is the position of industrial biotechnology in our global future? Adam M. Burja Agenda • • • • • • • Some Background The basis for modern industry is carbon What can biotechnology do? Contributes to the Carbon Initiative A positive effect on the economy A perspective from multi-national companies The future is bright Industrial Biotechnology • The application of biotechnology for industrial purposes, including manufacturing, alternative energy, and biomaterials. It includes the practice of using cells or components of cells like enzymes to generate industrially useful products • A transformative process that uses the tissues, cells, genes or enzymes of plants, algae, marine life, fungi or micro-organisms • An activity that uses a biotechnological process to produce and process materials, chemicals and energy Market Research • Biotechnology industry has mushroomed since 1992 • Worldwide Revenue ($bn): – 216.5 (2011); 270.5 (2013); 323 (2015); 414.5 (2017) • • • • 3.7% growth from 2011-2016 (CAGR 12.3%) Industry current employs 564,000 people globally 7,000 companies globally (2,500 in the US) One of the most research-intensive industries in the world. US biotechnology industry spent $35.4bn on R&D in 2014 Market Research • Capital raised by leading US regions vs Capital raised by leading European countries (2015) US Regions European Countries Graphs plot venture capital investment against innovation capital (defined as money raised by companies with less than $500m revenues, including private firms and therefore positively correlated to venture capital) The basis for industry is carbon • Modern industry uses the stored energy from sunlight first captured by plants through photosynthetic as… – Petroleum derivatives; or – Carbohydrates (e.g. cellulose, sucrose, glucose); or – Waste products (e.g. C1s: CO2, CO, syngas, CH4) • Cost driver is petroleum and sugar (sucrose) prices Biotechnology can be used to develop… – new products, – replace key industry intermediates • NREL Top Value Added Chemicals from Biomass – make existing products more efficiently • cheaper, better, cleaner, faster, etc. Industries that utilize biotechnology Biotechnology helps contribute to lowering carbon footprint • PARIS 2015 COP21 Climate Change Conference • Countries set a goal to limit global warming to less than 2°C compared to pre-industrial levels by the end of the 21st century • Legally binding on 22 April 2015 • Agreement encourages: – climate action by governments to enable a shift to a lowcarbon economy and – helps drive concrete actions, to reduce the carbon footprint • Companies that embrace CSR are on average 36% more profitable than those that don’t Recent advances in biotechnology • Synthetic Biology – Enabled by: – Miniaturization and automation – Development of new methods for synthesis and manipulation of DNA • Gene and genome editing technologies such as MAGE, CRISPR-Cas9, TALEN, Zincfingers and novel nucleic acid synthesis technologies Recent advances in biotechnology • Several countries have embraced this technology: – United States: • Synberc • DARPA 1,000 molecules initiative – United Kingdom: • A Synthetic Biology Roadmap for the UK – Canada – Others… Recent advances in biotechnology • Established industries have also biotechnology in general and synthetic biology in particular Established industries have also embraced biotechnology in general and synthetic biology in particular Case Study: Big Five Petroleum companies: – The low oil prices creates new opportunities and challenges for energy innovation. – Yet in this environment all multi-nationals have maintained or even continued to invest in Bioscience / Biotechnology / Bioindustrial capabilities. – Seen as disruptive technology in the field – In this environment, BP’s technology is focused on applying ready-to-go technologies everywhere they are needed, helping the businesses to be safer, smarter and faster. Case Study: • Since 2006, BP has invested over $4b in Alternative Energy Options • Develop low carbon transportation fuels not linked to petroleum market • In 2010 hired ‘Global Synthetic Biology Manager’ and acquired Diversa (San Diego) and four Sugar Cane Ethanol Facilities (Brazil) • In 2014 decision was taken to exit the Lignocellulosic ethanol biofuels business. • In 2015 established a Biosciences Center to sustain critical mass in biosciences capability, perfect current opportunities and assess future opportunities across BP’s businesses • Recently completed the construction of a purpose-built mixed laboratory and office site in San Diego. Case Study: • DSM – Bright Science. Brighter Living • Royal DSM is a global science-based company active in health, nutrition and materials • Uses biotechnology and material sciences to drive economic prosperity, environmental progress and social advances • Strong commitment to social responsibility: – CEO recently named co-chair of the Carbon Pricing Leadership Coalition – A group launched at Paris COP21 in December 2015. – The initiative aims to put a price on carbon emissions. The future is bright • Industrial biotechnology provides a means to: – Increase economic output – Provide highly-skill, high-paying employment in the private sector – Enable a shift towards a bio-based economy. One based on a production paradigm that relies on biological processes – Develop new and more efficient means of production which expend minimum amounts of energy – Reduce greenhouse emissions in production and energy generation – Minimize the production of waste as all materials discarded by one process are inputs for another – Realize low cost, secure energy Investing in industrial biotechnology – why & what Doug Cameron First Green Partners Aalto Design Factory Finland June 2, 2016 First Green Partners and a quick biosketch Perspectives on industrial biotechnology investment • Significance • Areas • Criteria Some representative examples First Green Partners What: Early-stage venture fund Nature's first green is gold, Her hardest hue to hold. Headquarters: Minneapolis from “Nothing Gold Can Stay” by Robert Frost Investment focus: Sustainable agriculture, food, energy, and materials Investment region: USA and Canada A quick biosketch Advanced Harvesting Systems, first job out of college Agricultural/industrial bio startup (large-scale protein separatation) MIT, graduate school Microbial production of R-1,2-propanediol (chiral propylene glycol) Department of Chemical Engineering, UW-Madison Microbial production of 1,3-propanediol Began work on 3-hydroxypropionic acid (route to bio-based acrylic acid) A quick biosketch (continued) Cargill lactic acid, polylactic acid acrylic acid non-caloric sweeteners Khosla Ventures Isobutanol, Gevo (Frances Arnold) fatty acids, LS9 ethanol, Lanzatech First Green Partners amino acids, Trelys Cargill/NatureWorks Polylactic Acid (PLA) OH O O O O OH O L,L-lactide D,L-lactide D,D-lactide Mainly L-lactic O CH3 CH3 O OH HO O O CH3 O n co-op communications Lactic acid processes: Cargill/NatureWorks pH > 4.5 (Traditional fermentation, Lactic acid bacteria) Lactic acid + Ca(OH)2 Calcium lactate + Lactic acid + H2SO4 CaSO4 pH < 3.0 (Novel process, Engineered yeast) Lactic acid extractant Finland Connection VTT Sisu Pirkko Suominen Lactic acid Cargill Erythritol Biorefinery BLAIR, NEBRASKA Cargil Lactic Acid Plant NW Polymer Plant Missouri River Evonik (lysine) Cargill Ethanol Cargill Sugar Refinery Cargill Corn Mill Cargill Corn Oil 10 650acres - 1 square mile-2.6 sq km-256 hectares A quick biosketch (continued) Cargill lactic acid, polylactic acid, VTT connection, Sisu acrylic acid non-caloric sweeteners Khosla Ventures Isobutanol, Gevo (Frances Arnold) fatty acids, LS9 ethanol, Lanzatech First Green Partners amino acids, Trelys Why invest in industrial biotechnology? From a business stand-point, the only reason to invest is to make a return on invested capital (ROIC) Otherwise, it is philanthropy (a gift) ------------------------------------------------------------------------------However, there is a spectrum from high to low returns Impact investors are open to making lower returns for greater environmental and social impact Industrial biotechnology can have a positive enviromental and social impact Our goal is investments with high returns PLUS positive impact Sustainable business Technical Technical Financial Financial Social Environ The what: Areas for industrial biotechnology investment Fuels and commodity chemicals Tough for venture capital Government grants and programs (EU, Climate KLIC) Private foundations (Breakthrough Energy) Large strategics (Total, Exxon, BASF, UPM, Stora Enso) Specialty chemicals/materials/agricultural chemicals Some venture capital interest Some family office/Impact interest Some strategic interest Food and food ingredients Significant venture capital interest Good Impact interest Good large strategic interest (General Mills, others) New effort led by Bill Gates Selected members: 3M AkzoNobel BASF Beierdorf AG Eastman Chemical HP Johnson & Johnson Nike Procter and Gamble SABIC Unilever Walmart The what: Areas for industrial biotechnology investment Fuels and commodity chemicals Tough for venture capital Government grants and programs Private foundations (Breakthrough Energy, KLIC) Large strategics (Total, Exxon, BASF, UPM, Stora Enso) Specialty chemicals/materials/agricultural chemicals Some venture capital interest Some family office/Impact interest Some strategic interest Agriculture and food Significant venture capital interest Good Impact interest Large strategics (Bayer, Unilever, Nestle, General Mills) Ag and food … some have estimated that it will take as much innovation in agriculture in the next forty years as in the preceding 10,000 years if we're to meet the demand for food. Tom Vilsack U.S. Secretary of Agriculture Source:http://www.usda.gov/wps/portal/usda/usdahome?contentid=2015/07/0194.xml&navid=TRANSCRI PT&navtype=RT&parentnav=TRANSCRIPTS_SPEECHES&edeployment_action=retrievecontent Ag and food (cont.) … over the past 10 years, we have made more progress incorporating food and tech than in the previous 1,000 years. Just two decades from now, your food life might be unrecognizable from the way it is today. ... it’s only going to get more interesting as our food world changes at such a rapid pace. Andrew Zimmern, host of Bizarre Foods, in Delta Sky, April 2016 Key considerations for early-stage technology investment Open minded to all early-stage technologies as long as they do not violate the Laws of Thermodynamics For an existing chemical, must have a route to be at least 30% cheaper than best available technology For a new chemical or product, must offer a 35x advantage over current solution How do companies meet previous considerations? Advantaged feedstock (biomass, CO2, H2 tailgas) High yields on feedstock Unique product (function, taste, purity, reactivity) Fast development cycle Some example companies and technologies Use of supercritical water to deconstruct wood and other biomass to: C5 sugars, C6 sugars, and high-quality reactive lignin Working with UPM, BASF, and Total (Germany) (Texas) Methane (Biogas) X Anerobic digestion Organic acids Waste biomass Chemical tranformation Fuels, commodity chemicals Specialty chemicals Malonate: A commodity chemical “sleeping giant”? Malonic acid 2/3 C6H12O6 + 2 CO2 ---> 2 C3H4O4 Y = 1.73 g malonic acid/g glucose CHO H2 “tailgas” to feed amino acids and other products (using engineered methanogenic archea) Yeast-produced silk proteins Steviol Stevioside Use heme produced by yeast fermentation Leather produced in animal cell culture A personal foundry? CREATE: CRISPR EnAbled Trackable genome Engineering Ryan Gill (CU-Boulder), Zhiwen Wang (Tianjin), et al. Thank you Doug Cameron [email protected] * PPP-models for bioeconomy Type Players example R&D / testing / technological innovation academia & industry, industry‐ industry BE‐Basic, EBI, CLIB, IAR, TWB, testing / pilot facilities Market development auctions, cooperatives, market place, (wood) pellets, sugar, agro‐ commodities, flowers, commodity / stock exchanges, vegetables, Etanol (BR) blending mandates, launching costumer Infrastructure industry & government, ngo (ecosystems services), agri‐cultural Rotterdam port extension, agri‐zoning, land consolidation* Sustainability criteria / certification industry, ngo, academia, (gov.) RSB + 100’s others, SCOPE / IPCC / Lorentz BioPanel Investment/ implementation (institutional) investors, industry, governments (state‐owned, subsidy), development banks (regional, EIB), Worldbank Group many (most) 2nd lignocellulosics plants multifunctional landscape (restoration) projects WB Role of PPP’s while driving the bioeconomy VTT | Espoo Finland | 02 06 2016 Erick Fernandes (Worldbank), Jan van Breugel (Corbion), Adrie Straathof (TUD), and Luuk van der Wielen (TUD/BE‐Basic) http://www.be‐basic.org/downloads * ruilverkaveling GHG balance & climate urgency: scale & scope – actual drivers • priorities & options • feedstocks – crude oil & biobased • feasibility & ‘role’ of advanced biofuels • (public-private) open innovation model -examples land use change • fossil, cement, steel contents atmosphere 18.4 bn T/yr 33.4 bn T/yr land 9.5 bn T/yr oceans 8.8 bn T/yr 3.4 bn T/yr Projected sea‐level rise and northern‐hemisphere summer heat events in a 2°C world and a 4°C world +0.8 o C = +1.4oF • Increased sea‐level rise from 70 cm to more than a meter • Increased frequency of extreme and unprecedented heat events • … and 75% of the poor in dev (agro) countries are hit first 1 Atmospheric CO2 is now higher than it’s been for 650,000 years and increasing rapidly Doubling ‘decades’ : process / agro / logistics are slow industries in 50 yrs 10000 Doubling in 50 yrs investment (mio euro’s) 400.26 ppm CO2 level as of February 28, 2015 agro & logistic systems 1000 commercial 100 demo pilot 10 new product, new application 1 existing product, new application 0,1 0 This graph, based on the comparison of atmospheric samples contained in ice cores and more recent direct measurements, provides evidence that atmospheric CO2 has increased since the Industrial Revolution. (Source: NOAA) High rate of change 5 10 15 20 25 years Example: Brazilian ethanol learning curve: 4x cost reduction in 30 yrs /20 x volume increase vd Wall Bake et al. Biomass & Bioenergy 33, 644-658, 2009 Fossil dynamics: impact on pension funds 1,06 NL pensions funds Legal minimum 105% (417 bn EUR) 1,04 1. So we have a time window of a few decades ! 1,02 2. Linked climate and economic impacts 0,98 400 bn EUR 1 -17% 0,96 3. 80% of GHG emissions already locked in existing capital stock 4. 2oC goal: less then 1/3 of proven fossil reserves can be consumed before 0,94 0,92 0,9 0,88 2050 (significant capital and renevue loss**) 0,86 apr-15 5. 70‐95 bn US$ in global annual adaptation costs 6. Impact investment ‐ required: $ 1…2 trillion in next decade (@10‐30% 350 bn EUR jul-15 sep-15 okt-15 dec-15 jan-16 mrt-16 mei-16 Total: 150…200 bn EUR capital loss -24% profit). 7. ABP mei-15 Pension funds : US $ 20 trillion, NL (EUR) 1 trillion AEX Scales of biorenewables (illustration) Tradeble biocommodities - Wood pellet market * Demand : stabilisation CO2 emissions of transport transport fuels = 2 billion ton (GT)/jr worldwide, annual growth 1.5% or 30 MT/yr (~120 MT/yr biomass) ` investments in 2nd generation production: → 200 plants or $ 50 billion every year → every 3 years an extra Port of Rotterdam (360 MT/jr) → (or every 5-6 years new Port of Shanghai) Potential: residuals & energy crops • maximum estimate • global total demand • average • double • current 50 100 300 450 700 EJ/jr 2 • • • • SCOPE / UNEP / UNESCO 137 authors from 24 countries of 82 institutes, peer reviewed BE-Basic 9 of 21 chapters Launches: Sao Paulo (FAPESP), Nairobi (UN), W’ton DC (Worldbank), Brussels (EU), * contents • urgency: scale & scope • priorities & options • feedstocks – crude oil & biobased • feasibility & ‘role’ of advanced biofuels • (public-private) open innovation model -examples Regional priorities: chemical NRW and NL are #1 and # 2 in Europe … this enables the largest industry cluster worldwide sector and transport w/o alternatives (aviation etc) #1 #2 CO2/ha/yr … in GHG emissions ! (so we have carbon to be recycled) mass yield: energy poor (O-rich) in materials* global production (MT/year) fuels 2000 (jet 300) cement 3000 (600 MT CO2) food 4000 (50% waste) CO2 glass 120 plastics 280 (big 5: 200) steel 120 (200 MT CO2) drop-outs ? biomass CH2O0.5 natural gas C crude oil O substitutes Biobased technology is/gets there “any” chemical can be produced from biobased feedstocks – by chemo / bio / thermo catalysis but not all make sense energy density increases cost (benefit) emission (reduction) resource efficiency yield is central parameter sugars, lactic ethanol drop-ins fuels (energy dense) & polymers (PE,PP, PS, PVC) H mass composition biobased and fossil feedstocks and products 3 “Drop-in Greenification” of Chemical Industry B substitute sustainable ethanol can green EU plastics industry fast A drop-in BIOMASS Biorefinery Gasification protein / sugar / lignocellulose Large scale ethanol-toethylene conversion is feasible in R’dam. tomorrow. Rotterdam Fermentation and other processes Aerobic Fermentation acetic other -acid Iso-butanol ethanol Iso-butylene Ethylene PETbottles plastics, Preservatives synthet. thickeners , plastics polymers glue Propylene Plastics, surfactants, detergents BioPVC Connected Ethylene Derivatives 18m Marl Geleen Feluy Tessenderlo Köln Jemeppe BioHydro carbons Frankfurt fertilizer methanol Plastics, carpet ARG Pipeline Ludwigshafen bio-ethylene products Connected pipelines =80% chemical industry From: Ton Runneboom Bio Based Chemicals March 22 2011, Rotterdam Roadmap for tech innovations in the Chemical and Energy sectors : “Shell and Cosan Form $12bn Ethanol Joint Venture Raizen 21/11/2011 2010 methane SNG glycerol Reforming Paraxylene Biopower 11m Oberhausen Antwerpen succinic acid tons Connected Ethylene Supply Terneuzen An-aerobic Funct. Lactic molecules acid ARG Connections Energy | liquid biofuels * * 2030 2020 System 2nd gen lignocellulosic EtOH commercial plants 1st gen. EtOH from sugar cane 2nd gen. advanced biofuels (hydro carbon-like) Amyris: “is scheduled to be in full production of Amyris 1st gen. advanced renewable products by Q2 liquid biofuels 2012. (hydro carbon-like) Abengoa Bioenergy: “1.3 million gallon/year capacity demo plant”.’09 2nd gen lignocellulosic EtOH pilot and demonstration plants Sime Darby-Mitsui: “convert oil palm empty fruit bunches, or EFB, into bioethanol”.2010 Low-cost lignocellulosic, thermostable enzymes Solution deploy Process * Engineering POET/DSM 250 M$ = 790 mRM (300 biomass > 160 ktpa sugars > 100 mio m3 ethanol) demonstrate DuPont 235 M$ = 744 mRM (200 ktpa hydrolysate sugars > 100 mio m3 ethanol) GranBio 147 M$ = 464 mRM (160 ktpa sugars > 82 mio m3 ethanol) ChemTex + Novozymes + DSM Low-cost lignocellulosic pretreatment technology for efficient fail-proof intermediate: low cost sugar (C5/6) platform * CO2 + solar light Develop (piloting) Basic Hardware based (3rd gen) biofuels DSM-TUD-B-Basic: “all you can eat yeast”.2011 C5 & C6 cofermentation ; biomass N –recycle HTE, -array bioreactors Genomics & (Directed) evolution Synthetic biology: novel pathways, robustness, rate and yield Genencor / Novozymes / photosynthetic micro organisms DSM: “commercial to excrete solar biofuels hydrolytic enzymes”.’10 Low cost photo bioreactor technology “the advances made by Joule Unlimited to achieve direct, continuous conversion of solar energy to renewable diesel at 15,000 gallons/acre/year ”2010 Implementing the Bioport Holland PPP concept Enabling Technology discovery Basic Science discovery * Aviation: GHG-reduction via TOI and jet biofuels * NL (bio)Fuelsmix 2050 Aviation 50% Marine 33% Road+rail 17% 40000 CO2 emissions (kton/year) in NL at 3% net growth of aviation fuels consumption 30000 Carbon neutral reference growth 35000 improved technology, operations, infrastructure 25000 biofuels 1G biofuels 2G biofuels tot aviation fossil biofuels total bio+fossil reference 20000 15000 proposed path 10000 KLM 1% biofuels in ‘15 5000 fossil fuels biofuels (1G+2G) 50% GHG emission wrt ‘05 2014 2016 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2038 2040 2042 2044 2046 2048 2050 0 International setting is critical for globally operating industries (transport & chemical) From “Visie Duurzame Luchtvaart”. SER Report Van der Wielen et al. June 2014. adopting NL to ATAG ambitions 4 * contents Introducing aviation biofuels (NL- numbers) Fuel-pool composition in 8000 (kton/year) at 3% net growth of fuels consumption 7000 8 (16) 7 mio ton/yr 2G: - 80% GHG 6000 • urgency: scale & scope • priorities & options • feedstocks – crude oil & biobased • feasibility & ‘role’ of advanced biofuels • (public-private) open innovation model -examples 6 (12) investment estimates [bn $] fossil 4 5000 mio ton/yr 4 Vandaag (8) (1G) 4000 3000 doubling jet fuelMorgen (2G) Biofuels (1G+2G) towards 90% biojet 2 (4) 150 kton/yr 1G: - 35% GHG 2000 fossil 1000 0.7 mio ton/yr 0 1 2015 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 2030 2050 Carbon neutral growth Platforms from biomass trends in biobased production concentration from reactor [kg/m3] 0,01 1 10 10000 1000 flavors & fragrances 1000 biopharma Glucose 1000 active ingredients 100 cost price ($/lb) 100 … and most of costs is (water) separation 100 bio-bulk 10 MAb, HSA 1 10 petrochemicals 1 antibiotics, nutraceuticals bioplastics 0,1 0,1 (PLA, PHA, PDO, ...) Cooney, ‘84 0,01 0,001 waste [kg/kg] 0,1 Xylose (2nd gen) biofuels 0,01 1000 100000 10 Plantation image from: biofuel.webgarden.com production [kT/yr] Cost contribution of feedstocks 600 feedstocks biomass yield $660/ton crude oil 0.25 palmitic acid 0.3 Hcomb 105 J/kg 0.34 lignine glycerol sugars biomass $400/ton $50..130*/ton $6/ton 0 Which platforms (redox/mass balance) ? products methane jetfuel/diesel p‐xylene ethanol 1,4 BDO 0.5 methanol 1.1 propionic acid adipic/acrylic syngas $1200/ton ethanol lignin ammonia $400/ton 3 sugars woodpellets $402/ton Only established market: APEX ENDEX Woodpellets ~ $130*/ton aromatics butanol butanol $800/ton succinic acid CO2 jet fuel crude oils Hcomb 105 J/kg lactic acid citric acid products platforms feedstocks hydrogen, electricity butanol propylene 0.4 1.0 $1600/ton ethylene 4,5 1,2 syngas lignin (p)ethylcarb. succinic urea 4,5 1,2,3 ethanol formic CO2 (4) CO2/biochem 30 5 Chemicals price model so far Oil price vs. sugar price (Europe) At 100% conversion 100% molar yield 0.80 0.80 London Sugar price (euro/kg) 0.70 0.50 0.40 0.30 0.20 oil €/kgproduct = €/kgfeedstock kgfeedstock/kgproduct 1.5 0.60 2010-2011 0.40 2012-2014 Feedstock costs 0.20 Rest 4 3,5 0.00 0.10 sugar 0.00 0.20 0.40 0.60 0.80 Cheaper product when less conversion steps from oil Brent oil price (euro/kg) 0.00 Jan‐10 Jan‐11 Jan‐12 Jan‐13 Predicted price ($/kg) Price (euro/kg) 0.60 Jan‐14 3 2,5 2 1,5 1 0,5 31 32 0 0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 Literature price ($/kg) Competitiveness compared to ethanol fermentation Calculation results 1. Poor: naphtha products (ethene, propene, butenes, BTX) 2.5 2.5 competitive 1,4‐BDO 1,4‐BDO adipic acid acrylic acid acetone) 2 butanone propylene phenol 1.5 Relative price (kg basis) Relative price (kg basis) 2. OK: mono alcohols (1-propanol, 2-propanol, butanols, adipic acid acrylic acid 2 propylene glycol ethylene isobutanol 1‐butanol isopropanol 1 ethylene glycol ethanol 0.5 butanone propylene 1.5 ethylene 1 phenol isobutanol 1‐butanol isopropanol ethanol 3. Good: diols (ethylene glycol, 1,2-propylene glycol, 1,4- propylene glycol butanediol) ethylene glycol 4. Very good: adipic acid, acrylic acid, methyl methacrylate 0.5 not competitive 0 0 0 0.2 0.4 0.6 0.8 1 Reported fermentation yield of product on glucose (g/g) 0 But is a 1-step conversion by fermentation (or chemocatalysis) achievable? 0.2 0.4 0.6 0.8 1 Stoichiometrically maximum yield of product on glucose (g/g) 33 contents 34 Biorefinery structure - biomass to integral value food/feed • urgency: scale & scope • priorities & options • feedstocks – crude oil & biobased • feasibility & ‘role’ of advanced biofuels • (public-private) open innovation model -examples harvest / logistics pretreatment / hydrolysis ‘switch’ conversion to fuels conversion to chemicals nutrients/water conversion to power/heat • tune portfolio value renewable energy/fuels/chemicals • counter-acting scale effects of logistics (5-10% for bagasse, fuel chemicals/ materials renewable power/heat 30% for palm oil biomass) and conversion costs • energy/heat, water, and nutrient integration • need for cross-industry sector collab’s (JVs, trade, co-op’s,…) 6 2013: 5 fairly different designs Winning Team 2013 LST MSc Design Competition woodpellets + … power/heat + ethanol + biochemical + €€ (instead of –SDE) 1,2 PDO H2O 50 Acrylic acid 2 EC O2 240 Ethe ne PE PP 100 2 400 Biosene Wood Chips 4000 ktpa 2 H2O 490 H2 60 i-Butanol 50 i-Butene 50 CO 400 H2O 100 2 opt CO 1,4 BDO 914L 380 H2O Succini c acid CO 100 GTB E PX Methanol 2 MCA Acetic acid i-Butene Syngas DMC 39 700 Succini c acid Wood Chips 4000 ktpa i-Butanol 250 CO 1,4 BDO Biosene Acetic acid 686L Syngas H2 30 THF Ethanol MCA 100 3HP Ethe ne PE PP THF H2 CO 920 100 PX SHC MEG 100 225 Ethanol 2 GTB E SHC 3HP CO 2 1,3 PDO Lactic acid EtOx 100 CO 250 opt 100 100 50 MEG CO 1,3 PDO Lactic acid H2O H2O Acrylic acid PLA EC 100 EtOx 1,2 PDO PE C H2O PLA CO 100 DMC Methanol 40 Authors: Kim Meulenbroeks/ Jan van Breugel 40 REDEFINERY to produce sugars and fuels 500 Coal value Equal to wood 400 o – transfer price for lignin priced as wood at target NPV Bunker oil & Kerosine o 4 Mt/a various scales NPV>0 300 €/t sugars PE C 1.5 Mt/a 200 London #5 Sugar Price (26/06/2015) NPV<0 100 New York #11 Sugar Price (03/07/2015) 0 0 200 400 600 €/t lignin 800 NPV= 0 at various scales wood chips at ‘mid price’ cost of /return on capital at market conform pricing included Presentation based on public data 7 contents * Open innovation model in shells relevant fields, scout/set options-trends inspiration vv, HR-PR-reputation <100> • relevant academics/fields, scout IP science foundation, inspiration vv, HR-PR <10> urgency: scale & scope conferences • priorities & options • feedstocks – crude oil & biobased • feasibility & ‘role’ of advanced biofuels • (public-private) open innovation model -examples • background knowledge, generate IP public private HR-PR <4> • alt.: VC-fund, monitor deal flow IP private-private <4..10> ‘nice to know’ strategic access to IP & skills, JV or B2B partners <1..2> differentiating, full IP <1> necessary core + innovation budget + FTE (incl follow-up) joint ventures BE-Basic, other PPS science foundation, EU, ... <x> multiplier = (project $ / company $) budget : risk – impact mapping About us: www.BE-Basic.org/downloads * RD & Innovation strategy B-Basic & Ecogenomics 2004-2009 B-Basic 2004-2010 BE-Basic 2010-2015 spin- in via partners fuzzy front end new processes and products wild ideas new companies lab R&D high risk demo plant pilot plant full plant unbound unbound new monitoring methods new approaches (e.g. Smart Soil for CO2 capture) failure is an option early spin-outs DISCOVER DEVELOP DEMO DEPLOY Focus: (1) start-ups , (2) training bio-engineers, (3) pilot facilities * Bioprocess Pilot Facility at Delft Biotech Campus N operational since mid 2012, while being renovated (www.bpf.eu) 80 M€ public-private investment Bioprocess Pilot Facility at Delft Biotech Campus N operational since 2012, renovation complete 2014 (www.bpf.eu) 80 M€ public-private investment 8 Synthetic Biology in the real world? glucose Successful SME’s in BE-Basic (Q1 2013) • TUD-spin-out discovered FDCA-technology for sustainable PET- xylose replacement (’09), developed in BE-Basic (’10-’11) for further arabinose commercialisation in Corbion (mar’13) acetate • glycerol WUR-starter pioneer in chemicals from waste streams, closes series A investment furanics with Horizon3 and DGF* (5 apr 2013) • DḀB TUD starter (oct’12) with BPF, TUD, VC develops advanced biorenewables processes commercial product based patent portfolio … and more to come ! trends in biobased production The other 70% : FDCA for “BioPEF” • Top-12 value-added chemicals from biomass concentration from reactor [kg/m3] 0,01 • Platform chemical - market size 4-12 bn $/yr • Replace terephthalate in 15 mio ton polymers • Concept in B-Basic (TUD/TNO - ’09) – FDCA direct production from lignocellulosic HMF 10 kg-scale process biomass cost price ($/lb) 1000 • indust biocat (BIRD Eng /TUD-’09) – bioprocess (BIRD –’10) – invest round - piloting (BE-Basic-’11) • 2013 - acquisition of BIRD Eng / FDCA by Purac 1 100 1000 10000 biopharma active ingredients 100 bio-bulk 10 MAb, HSA 1 petrochemicals bioplastics 0,1 (PLA, PHA, PDO, ...) Cooney, ‘84 0,01 0,001 HM-furOH Bioconstruction materials (self-healing, cement, bioconcrete,biogrout, bioasphalt,, …) antibiotics, nutraceuticals 0,1 10 (2nd gen) biofuels 1000 100000 production [kT/yr] Biogrout & bioconcrete: from soft soil to rock solid 100 micrometer (10-4 m) In-situ concrete by carbonate fixation Van Paassen Animations © 9 conclusions Combined (drop-in/substitute/-out) scenarios ? 600 products feedstocks methane biomass yield $660/ton crude oil 0.25 palmitic acid 0.3 Hcomb 105 J/kg 0.3 lignine 0.4 0.5 $400/ton glycerol sugars biomass $50..130/ton 1.0 • ethylene industry, far ‘beyond bioethanol’ and advanced jetfuel/diesel fuels p-xylene butanol propylene ethanol 1,4 BDO methanol propionic acid adipic/acrylic syngas lactic acid succinic acid connect 2 sectors w megavolumes 1.1 citric acid $6/ton 0 CO2 biorenewables can play critical role in chemical & materials bioconstruction • in sustainable (people, planet, profit) development • no premiums & subsidies: need to be integral part of chemicals/ fuels/ food/ energy /logistics system • fuels with priority for sectors w/o alternatives • public-private partnerships are required to speed-up development and implementation, in professional setting 55 10 Ecosystems for business From incubator spirit to investor interest By @matthewmarkus (substituting for Richard Yu) Who am I? contemporaries invested in pembient Incubator Richard Yu, Director Accelerator Startup Matthew Markus, CEO Incubator vs. accelerator? Incubator Accelerator Selection Restricted Via open application Intake Continual Cohorts Duration 1-5 years 3 months Model “Talent pool” “Pressure cooker” Mentorship Limited Extensive Focus Academic Industrial Equity stake None 6-8% “Demo” day No Yes Focus on IndieBio… “Biotech has expanded from a drug based world to now include everything.” — J. Craig Venter Investment themes ● ● ● ● ● ● ● ● ● Consumer biotech Post-animal bioeconomy Future of food Neuroscience Medicine 2.0 Regenerative medicine & gene editing Microbiome Exobiology Immunology Sampling of the portfolio… Pembient Animals are Precious Traditions are Important Rhino Horn Wild Biofabricated ??? $12k/kg Wild Horn $8k/kg Reseller +192% +338% $35k/kg Asymmetric Information Buyer Biofabricated Horn Resellers $35k/kg $35k/kg $35k/kg ??? EV = $8,750/kg Adverse Selection Buyer $35k/kg 1. Markup on cost of biofabricated horn entices resellers. 2. Probability of buying a biofabricated horn increases. 3. Expected value of any given horn decreases. 4. Market equilibrium resets. 5. The cost of biofabricating horn decreases. — based on — The Market for Lemons Quality Uncertainty and the Market Mechanism by George Akerlof, Ph.D. Published: 1970 Nobel Prize: 2001 “What’s past is prologue.” — William Shakespeare ● ● ● ● ● Since 5/2015 $50k for 8% $25k CLN 10 startups/year BSL-2 lab ● ● ● ● ● Since 2/2015 $50k for 8% $150k CLN 30 startups/year BSL-1 & BSL-2 lab IndieBio EU founded ● ● ● ● ● Since 1993 Cork, Ireland $250m AUM 6 accelerators Global rebranded ● ● ● ● ● Since 5/2014 Cork, Ireland $30k in funding Bench space Mentorship IndieBio SF Who is IndieBio SF? Arvind Gupta Managing Partner Ryan Bethencourt Program Director Involved with Berkeley Biolabs & Counter Culture Labs Ron Shigeta Scientific Officer Involved with BioCurious & Berkeley BioLabs “Geography is destiny.” — Napoleon Bonaparte (attributed) “The Edge… there is no honest way to explain it because the only people who really know where it is are the ones who have gone over.” — Hunter S. Thompson Metrics of success ● 93+ mentors, including: ○ ○ ○ ● 42+ companies, including: ○ ○ ○ ● George Church, Professor, Harvard Medical School Isha Datar, President & CEO, New Harvest Linda Avey, Founder, 23andMe Clara Foods with $1.7m seed round Memphis Meats with $2.75m seed round NERD Skincare with $1m seed round Publicity: ○ ○ 4000+ Twitter followers TechCrunch, Fast Company, Forbes How can the Finnish investors respond to enable growth in the field? Financing opportunities for Finnish growth companies Industrial Biotechnology Business Seminar Eeva Grannenfelt 2.6.2016 Grannenfelt Finance Ltd Grannenfelt Finance is an independent family-owned provider of financial solutions for SMEs and growth companies, established in 2015 Our goal is to find comprehensive funding solutions for SMEs and growth companies that support growth during the entire life cycle of the company – thus enabling businesses to focus on growth without a constant worry about the funding Today’s funding opportunities are diversified and fragmented outside the conventional banking sector to private, government and EU solutions We combine the suitable funding options effectively to our customer’s individual needs Society Should Create Opportunities and Remove Obstacles Wide-ranging funding solutions Banks Insurance Companies Pension Funds Venture Capital International investors, private equity and loan funds Private Equity Funds Loan Funds Family Offices Stock Markets Business Angels ARMADA Government/EU funding Crowdfunding Life cycle financing • • • • • • • • Tekes Ely-center Finnvera Angels Seed-funds Venture funds Crowdfunding Banks *Valley of death 1. Start-up • • • • • • Finnvera EIB Banks Pension and insurance funds Venture funds Loan funds • • • • EIB Banks Buyout-funds Late stage venture funds ***Valley of death 3. **Valley of death 2. Internationalization * First valley of death appears in ** Second valley of death the early stage of company life appears when company is cycle entering to the global markets • • • • IPO Banks EIB Capital markets Growth *** Third valley of death appears while problems arise from global leadership and from cultural differences Stability http://techcrunch.com/2015/11/11/nokiasfall-means-the-rise-of-startups-in-finland/ The most exciting startup scene you have never heard of isn't in Seattle, or London—it's in Scandinavia. "There's been a rise of startup communities in Finland and other Nordics as well. These communities function at the intersection of municipality, corporations and academia, bridging gaps and opening up exciting opportunities for their startups," said Panu Keski-Pukkila, founder of Hardware Startup Finland. http://www.slate.com/blogs/moneybox/2015/12/18/the_n ordic_startup_scene_is_second_only_to_silicon_valley.html Grannenfelt Finance Fredrikinkatu 35 B 11 00120, Helsinki www.grannenfeltfinance.fi Eeva Grannenfelt Lasse Grannenfelt +358 50 544 6355 [email protected] +358 40 717 8572 [email protected] Rational design of microbes for competitive biotechnological processes Isabel Rocha, CSO [email protected] 2016-06-02 www.silicolife.com in silico design of optimal cell factories - Founded in 2010 and privately owned by its founders - Enabling the design of optimized microbial strains for the production of biofuels, chemicals or biopolymers - Player in the design step of the synthetic biology cycle, using models, simulation and optimization - Bridging computer sciences, life sciences and bioengineering - Working with leading chemical, materials and synthetic biology 2 companies Industrial Biotechnology 3 Improve the economics of the processes - Productivity: - Yield: - Specificity: investment costs raw material consumption investment and operational costs Improve the microbe 4 Improving the microbe To produce desired products it is generally necessary to retrofit the metabolism. Where to start???..... Raw material Product By-products 5 5 The GPS analogy… ? ? ? ? ? GPS ? Carbon Source 6 Desired Product 6 A complete pipeline from the problem to the solution Problem from client Development Partners ? Strain optimization for desired end product Using computational biology to tailor metabolic pathways Network of partners: Wet lab Genome sequencing State-of-the-art from Academia 7 Synthetic biology recombining nature diversity In silico screening of genes from heterologous organisms Evaluation of yield opportunities for reaction alternatives Selecting the most efficient heterologous genes 8 Designing new synthetic pathways ? 1. Characterize the transformation ? ? 2. Identify enzymes performing similar transformations 3. Enumerate putative enzymatic options from source to target Discovery of new activities and pathways Exploration of promiscuous enzymatic activities Evaluation of the use of alternative substrates with similar functional groups Enumeration of alternative pathways and intermediates 9 Working with leading chemical, materials and synthetic biology companies Contracted projects with: Fortune 500 companies Multinational conglomerates World leading agri-business companies Global leaders in building block chemicals, polymers and biosynthetic development 10 Collaborating in R&D projects Selected national and european projects: • H2020 – DD-DeCaF – Bioinformatics tools for industrial biotechnology • FP7-KBBE: BRIGIT, Biotechnology for novel biopolymers, 2012. • ERA-IB-2: DeYeastLibrary, Designer yeast strain library optimized for metabolic engineering, 2014. • ERA-IB-2: ICPRES, Integrated Process and Cell Refactoring Systems for Enhanced Industrial Biotechnology, 2014. • ERA-IB-2: DYNAMICS, Analysis and optimization of industrial microorganisms under dynamic process conditions, 2015. 11 A multidisciplinary team which includes expertise in the Life Sciences, Bioengineering, Computer Science and Bioinformatics with > 15 people. Executive team Simão Soares Isabel Rocha Chief Executive Officer Chief Scientific Officer MSc Bioinformatics BSc Informatics Engineering Board member P-Bio PhD Chemical Engineering UMinho Faculty Founder Biotempo Miguel Rocha Paulo Vilaça Chief Technology Officer Chief Operations Officer PhD Computer Science UMinho Faculty Bioinformatics expert MSc Bioinformatics BSc Informatics Engineering Bruno Sommer Ferreira Chief Business Development Officer PhD Biotechnology Biotrend CEO 12 Designing the new generation of bio-based products Address SilicoLife Lda. Rua do Canastreiro, 15 4715-387 Braga PORTUGAL Phone +351 253 540 107 E-mail [email protected] Isabel Rocha, CSO [email protected] www.silicolife.com OptFlux: a metabolic engineering open-source show-case More info www.optflux.org OptFlux: an open-source software platform for in silico metabolic engineering. BMC Systems Biology 4:45, 2010. 14 @note2: a biomedical text-mining platform Publication management Information retrieval and extraction User-friendly Plug-in based and opensource More info www.anote-project.org 15 HIGHLY EFFECTIVE ENZYME SOLUTIONS FOR CELLULOSIC BIOMASS CONVERSION METGEN AT A GLANCE • MetGen develops and markets enzyme solutions into growing biomass markets within the energy, pulp and paper, packaging, polymers and plastics sectors • The majority of biomass conversion processes have low yields, consume large amounts of energy or chemicals and are highly capital intensive • Enzymes are the preferred and most sustainable solution to convert cellulosic biomass into valuable fibers, renewable fuels and chemical building blocks • MetGen’s industrial enzymes enable cellulosic biomass conversion at high yields and low cost • The unique MetGen enzymes are tailored to withstand harsh industrial environments (extreme pH, high temperatures, presence of inhibitors) • The enzymatic performance has been validated in multiple industrial trials • The fermentation process allows competitive enzyme production cost OUR MISSION EMPOWERING INDUSTRIES TO ENHANCE VALUE OF BIOMASS USING ENZYMATIC SOLUTIONS ENZINE® TECHNOLOGY PLATFORM • • • • FAST: Industry leading short development cycle Technical support FLEXIBLE: Tailored enzyme design approach to meet challenging industrial conditions ADAPTABLE: Can produce large amounts of different enzymes, cost-effectively PROVEN: Developed three novel enzymes from concept to validation at industrial scale and production Industrial supply of enzyme Identified Customer Challenge Unique Combination Piloting and scale-up Application testing Designing, cloning and screening UNIQUENESS OF ENZINE® PLATFORM • • • • • Dedicated Technical Support Industrial scale enzyme production Cost-effective, efficient process Pilot fermentation facility with downstream processing Fast-track to industrial production including optimized strain and production protocol Technical support Industrial supply of enzyme Identified Customer Challenge Unique Combination Piloting and scale-up Application testing Designing, cloning and screening • • • • • • Continuous IP landscaping Unique genetic engineering capabilities Extensive libraries of highly potent clones In-depth knowledge of client requirements and applications Special testing equipment Protocols for industrial scale testing MANAGEMENT TEAM Alex Michine Klara Birikh Matti Heikkilä CEO R&D Director CTO Sami-Pekka Rantanen Toni Grönroos Antoine Mialon Sales Director Solution Development Manager Application Team Leader METGEN INDUSTRIAL ENZYME SOLUTIONS Pulp and Packaging • • • • Energy and cost savings Product quality improvements Process improvements Sustainability improvements Biorefineries • • • • Lowering overall enzyme costs Higher sugar yields Less CAPEX through more compact processes Novel biochemicals from lignocellulosic sugars Product BRILATM FORICOTM SEKALOTM POVONTM Application MECHANICAL PULPING TISSUE EFFLUENT CONTROL PAPER COATING FLUTING LINER WOOD CHIPS REJECT PULP DEINKED PULP RCF EFFLUENT STARCH CHEMICAL PULP NSSC Efficiency and Energy Saving Quality & Process Improvements Energy & Raw Material Savings Peroxide Removal Improved Biogas production& Water treatment Economic Starch Conversion Quality & Process Improvements Energy & Raw Material Savings Benefits LIGNOTM Enzyme Added to METZYME® PRODUCT FAMILIES FOR PULP AND PACKAGING METGEN STRATEGIC FOCUS: Lignocellulosic biomass conversion in multiple segments PULP AND PAPER VOLUME OF LIGNOCELLULOSIC RENEWABLE CHEMICALS BIOFUELS BIOMATERIALS MetGen process cellulosic biomass into pulp/fibers or cellulosic sugar. Value-added products are made of these intermediates Packaging, Tissue, Paper Biobased plastics Energy and liquid fuels Nano cellulose METGEN GO-TO MARKET PLAN STRENGTH INCREASE ENERGY SAVING BIO REFINERY EU Rollout Americas First EU sales Pilot trials 2016 Industrial trials Global EU Rollout N.America Global Global Sales 2017 2018 MetGen’s current markets for enzymes are • Fiber Strength increase and process improvements in tissue and packaging board production • Energy Saving In wood pulping processes • Cellulosic biomass hydrolysis and sugar conversion in biorefineries • Cellulosic sugar isomerization for renewable plastics RECYCLED FIBRE & DEINKED PULP STRENGTH IMPROVEMENT MetZyme ® BRILATM dosed on RCF or Virgin fibre Tissue or Board machine Challenge Unplanned downtime machine costs around €1 Mln p.a Solution MetZyme® BRILA™ improves product properties Results Product breakage decrease up to 60% and downtime reduced by 50% Value Proposition Net Savings to Mill € 0.5 Mln p.a Reference Industrial Mill trials CHEMICAL PULP / NSSC STRENGTH IMPROVEMENT MetZyme ® POVON TM dosed on NSSC Fluting paper machine Challenge Paper machine runability issues Unplanned downtime machine costs around €1 Mln p.a Solution MetZyme® POVON™ improves strength properties Results Paper machine web-breaks decreased up to 60% Value Proposition Net Savings to Mill € 1 Mln p.a Reference Industrial Mill trials at >300 000 tons p.a PULP PROCESSING - ENERGY SAVING Wood chips treated with MetZyme ® LIGNOTM Pulp production in refiners Challenge Average mill spends €20 million/year on energy, refining is 50% of the electricity bill Solution Reduce energy consumption by treating wood chips with MetZyme® LIGNOTM Results 20% less electricity consumption and final product strength increased 10-15 % Value Proposition Net Savings to Mill operator €1.5 Mln p.a Reference Industrial Mill trials PEROXIDE REMOVAL FROM EFFLUENT FLOW MetZyme® FORICO TM added to reactors Effluent treatment facility Challenge Wastewater, normally used in biogas production, can’t be used if contaminated with residual peroxide Solution MetZyme® FORICO™ deactivates residual hydrogen peroxide when applied to aerobic effluent reactor Results Residual hydrogen peroxide fully degrades in under 1 hour Value Proposition Case by case Reference On going commercial supply to paper mill STARCH CONVERSION FOR PAPER COATING MetZyme® SEKALO TM added to pure starch Paper machine Challenge The high cost of starch modification Solution Substitute chemicals for MetZyme® SEKALO™ to lower cost Results Same surface strength, lower costs Value Proposition Mill saves €400,000/year on average Reference Mill Trials BIOREFINERIES - CELLULOSIC SUGARS MetZyme ® SUNOTM added to pretreated biomass Conversion to sugars Challenge High enzyme cost with challenging lignocellulosic biomass Inhibition at high consistency of biomass High capital and operating cost Solution MetZyme® SUNO™ Tailor-made Drop-in solution Results Sugar yield increase 20% or enzyme dosing decrease of 50% Biomass consistency >20% More compact processes and lower CAPEX Value Proposition 15% savings in sugar production cost Reference Pilot scale & H2020 Projects BIOrescue and ButaNexT BIOREFINERIES – RENEWABLE PLASTICS MetZyme ® PURECOTM glucose isomerase added to hydrolysate Conversion to sugars Challenge High enzyme cost with challenging lignocellulosic biomass Commercial enzymes are inhibited by biomass Solution MetZyme® PURECO™ Glucose Isomerase Results Isomerization in non-purified hydrolysates Better stability, yield increase and total productivity increase More compact processes and lower CAPEX & OPEX Value Proposition Enabling technology for lignocellulosic plastics Reference Lab scale H2020 projects ReTAPP and BIOFOREVER LONG TERM OPPORTUNITIES MetGen aims to drive profitable growth in global markets New and sustainable bio-based materials Renewable alternative to petrochemicals Clean & safe environment PULP & PAPER ENZYME COCKTAILS NANO CELLULOSE BOARD STRENGTH TISSUE ENZYMES RENEWABLE CHEMICALS Technical Industrial support XYLOSE supply of ISOMERASE enzyme XYLOSE AND FURFURAL XYLOSE REDUCTASE XYLITOL Desing, cloning and screening WASTEWATER TREATMENT OXIDOREDUCTASES PHENOLS REMOVAL MetGen is helping the bio-based industries materialize their full potential ENZYMES FOR BIOREFINERIES. WHAT’S NEXT? Ready for optimization Nanocellulose Candidate enzymes for development (MetZyme®PURECO™) MetZyme ® LIGNO™ Aldose reductase Sorbitol Value-added products Cellulose C6 (Glucose) Fructose HMF MetZyme® PURECO™ MetZyme® LIGNO™ MetZyme® SUNO™ L-Xylulose D-Xylose reductase BIO MASS Hemicellulose Xylanase, Xylosidase C5 (D-Xylose) Xylitol Xylitol-4dehydrogenase Xylosidase Acetyl xylan Esterase D-Xylulose MetZyme® PURECO™ Lignin Xylose isomerase Furfural Chemical derivates of Lignin Opportunity in MDF Board strength improvement MetZyme® LIGNO™ added to wood mass Plywood Hot-pressing Challenge Increasing MDF board strenght Solution Treating fibers with MetZyme® LIGNO™ may increase of internal bond strength Results Need to be verified in relevant scale Value Proposition 30– 50 % internal bond strength Reference Scientific articles WASTE WATER APPLICATIONS MetGen laccases added to waste water Normal waste water treatment with decreased COD, phenols and other micropollutants Challenge “Hard COD”, phenolic compounds and other micropollutants Solution MetGen laccases reduce COD and micropollutants Results Reduction of 40% of COD and phenols from pulp and paper mill waste water. Significant reduction of various micro pollutants using synthetic solutions (e.g. >95% reduction of Bisphenol-A) Value Proposition Further technical solutions required before commecial application. Legistlation does not require redution of micro pollutants at this time. MetGen provides ability to foresee the change in regulation. Reference Laboratory trials using industry waste water (COD & phenols) and synthetic solutions (micropollutants) REDUCING MICROPOLLUTANTS FROM WASTE WATER MetGen’s laccases have been tested in laboratory on synthetic micropollutant solutions. In these test to significant reduction of various laccases added micropollutants was demonstrated waste water in laboratory scale. Diclofenac Estradiol Estrone Ethynilestradiol Triclosan Bisphenol-A Nonylphenol Carbamazepine Naxopren Anthracene Benzo(a)pyrene Phenanthrene Pyrene WASTE WATER APPLICATION STATUS • MetGen began testing the molecules on industrial waste water already in 2005. • Due to the lack of enforced legistlation there was no interest to reduce the micro pollutants in waste waters • MetGen has IP on the enzymes • MetGen has on-shelf enzymes designed for harsh conditions • MetGen has the capability to produce the required enzymes in industrial scale. • MetGen is interested to collaborate on developing technical solutions for a commercial application in waste water treatment: – ”Single-use” enzyme may not be the most affordable solution for waste water treatment – Commercial application may require immobilization of the enzymes to be used more than once for improved economics WHY METGEN? • Repeat demonstration of outstanding enzyme performance in harsh industrial environments • Customer adopted enzymatic solutions that address customer needs • Industry leading short development cycles for new enzymatic solutions • Versatile plug&play enzyme expression platform • Multiple market ready enzymatic solutions tested at industrial scale • Commercial production capabilities using qualified European contract manufacturers • Lean business model with low breakeven point LASTING SOLUTIONS FOR CUSTOMER ARE ALWAYS BUILT THROUGH COLLABORATION R&D Team Technical Team Business Team Identification and development of MetZyme® solution addressing these challenges. Together with mill team, identification of optimal place in process to apply MetZyme® Commercialization of product Sales Contact Process challenges are discovered while meeting with mill personals Application Testing Team Technical Team Technical Support Team Reporting on test results MetGen has achieved with customer specific material (pulp, biomass, process water) using selected MetZyme® prototypes. Further optimization of specific product and application for customer Continuous technical support for product implementation and better results FUNDING PARTNERS & COLLABORATORS Equity investors HST Partners Oy Collaborators Goverment VISIT METGEN.COM [email protected] Enabling the use of CO2 as an industrial fermentation feedstock EnobraQ Confidential 1 What if CO2 was part of the solution … …and not only an issue? EnobraQ Confidential 2 What if we could produce competitive and yet sustainable chemicals? What if you could buy sustainable and yet competitive chemicals? EnobraQ Confidential 3 From academic research to start up development 2011 2012 2013 TWB inception 2014 2015 2016 2017 Carboyeast extension Carboyeast period Carboyeast project started EnobraQ inception Fully operational Series A EnobraQ period SGSF 1st tranche investment EnobraQ Confidential 2nd tranche investment 4 EnobraQ tries to reverse what has been attempted What people usually do: Trying to domesticate new microorganisms that already have photosynthetic/"gas-trophic" capabilities but that no one knows how to use it industrially What we do : Develop autotrophic capabilities on well known industrial fermentation "existing working horse" like yeasts Slow and painful metabolic engineering development Most of the technical risks are upfront (initial metabolic engineering) Scale up and industrial uses of these organisms is a complete "terra incognita" with very high profile risk Scale up and industrial uses of yeasts are very well known and is somehow predictible EnobraQ Confidential 5 Technology concept Three simple concepts : 1. Modify a yeast in order to enable it to use CO2 as a plant 2. Use hydrogen as a convenient source of energy (instead of light) 3. Use it to produce valuable chemicals leveraging on existing pathways Cheap feedstock compared to other sources of carbons Dark reactions involving RubisCo CO2 yeast chemicals H2 Efficient and practical source of energy and atoms Energy through hydrogenases Industrially proven organism ready to be modified EnobraQ Confidential Wide portfolio of possible products by genetic engineering 6 Compare to sugar, our feedstock is much cheaper Sugar price for the last 30 years and sugar cost equivalent to EnobraQ feedstock cost Worst case today Average case today Best case today Projection in the future EnobraQ will provide a dramatically lower feedstock cost that : • increases margins on existing commodity markets • unlocks very large new drop in markets EnobraQ Confidential 7 Complementary skills with a lean management An R&D outsourced model similar to pharma startups Cedric Boisart CTO Michael Krel CEO • 6 years leading business development efforts in two French IB ventures • 3 years of VC activity in IB and renewable chemistry • Former consultant with a PhD in organic chemistry • 15 years of experience in industrial biotech • Former Strategic Development Manager with Soufflet Biotechnologies • Former CTO of Carbios, leading the partnership with TWB • Led the bioinformatics team of Metabolic Explorer Leveraging expertise from TWB (more than 250 biotech scientists and engineers) with a 15FTE team EnobraQ Confidential 8 A full skillset around the table Board members Denis Lucquin Managing Partner @Sofinnova Leopold Demiddeleer, chairman Former head of New Business development with Solvay Nathalie Turc Observer Deputy director of Institut Carnot 3BCAR Scientific advisors Denis Pompon Philippe Soucaille Stephane Guillouet lead scientist on hydrocortisone project industrialized by Sanofi Lead scientist on 1,3 PDO project industrialized by DuPont lead scientist on European Alphabird project Top academic skills with strong collaborative industrial experience EnobraQ Confidential 9 EnobraQ highlights • Patented breakthrough science from top tier academic teams based in France • Process leading to shut down economics in several commodity industries • Lean and experienced management leveraging TWB labs • May attract investments and interests outside classical IB players because of CO2 utilization • Strong leverage of public financing EnobraQ Confidential 10 Enabling the use of CO2 as an industrial fermentation feedstock [email protected] Confidential +33EnobraQ (0)6 31 21 31 86 11 Living Factories Industrial biotechnology in Finland - the path forward Tanja Dowe, Innomedica Ltd 03/06/2016 Living Factories Creating Bioeconomic Growth– Industrial Biotechnology Business Seminar Espoo, Finland 2.6.20161 Living Factories Synthetic Biology in Finnish bioeconomy 03/06/2016 2 Living Factories Same old biotechnology... or not? 2016 2003 The human genome project completed: 13 years USD 2.7 billion An individual’s or production organism’s genome sequenced: 3 days USD 1000 ... ... ... Illumina Hi-Seq X Ten Synthetic Biology 1800 disease genes 350 products in clinical trials CRISPR 2000 genetic tests CHASSIS ORGANISMS BIOIT 03/06/2016 3 Living Factories The potential of synthetic biology in bioeconomy New conversion pathways & production organisms Existing bioeconomy raw materials Plant oils Sugars Microbial oils 03/06/2016 Existing products Biofuels Chemicals Materials 4 Living Factories The potential of synthetic biology in bioeconomy New bioeconomy raw materials CO2 Methanol H2 Waste New conversion pathways & production organisms Existing bioeconomy raw materials Plant oils Sugars Microbial oils 03/06/2016 Existing products Biofuels Chemicals Materials 5 Living Factories The potential of synthetic biology in bioeconomy New bioeconomy raw materials CO2 Methanol New products Chemicals H2 Waste Polymers Biosynthetic materials New conversion pathways & production organisms Existing bioeconomy raw materials Plant oils Sugars Microbial oils 03/06/2016 Existing products Biofuels Chemicals Materials 6 Living Factories The potential of synthetic biology in bioeconomy New bioeconomy raw materials CO2 Methanol H2 New products Synbio: Chemicals Waste DNA sequencing DNA synthesis Bioinformatics Biosynthetic materials Biologic components Existing bioeconomy raw materials Plant oils Sugars Microbial oils 03/06/2016 Polymers New conversion pathways & production organisms Sustainability Cost-efficiency Integrated systems Pharmaceuticals Energy Chemicals Existing products Biofuels Chemicals Materials 7 Living Factories The potential of synthetic biology in bioeconomy New bioeconomy raw materials CO2 Methanol H2 New products Synbio: Chemicals Waste DNA sequencing DNA synthesis Bioinformatics Biosynthetic materials Biologic components Existing bioeconomy raw materials Plant oils Sugars Microbial oils Raw material owners New conversion pathways & production organisms Sustainability BioIT comps Synbio tech start-ups Investors Pharmaceuticals Energy Chemicals Integrated systems Existing products Biofuels Chemicals Materials Cost-efficiency Universities and research centers 03/06/2016 Polymers CROs End-product companies Infrastructure providers 8 Living Factories Ecosystems and initiatives Biosustainability Center IBC Finland/ LiF CLIB Toulouse White Biotechnology BEBasic ERASynBio CSynBio acib strategic vision UK 60 M£ EU ERASynBio DOE 10 MUSD 17 MEUR SynBERC Synthetic Biology NSF 70 MUSD CHINA 30 Roadmap for the UK MUSD USA National Opprotunities for Bioeconomy Blueprint Scotland in synthetic biology iGem 03/06/2016 9 Map: galleryhip.com Living Factories Finland? We need spearheads for economic growth We have a legacy of industrial biotechnology We need to collaborate 03/06/2016 10 Living Factories Roadmap Vision With synthetic Biology towards sustainable bioeconomy Majority of industrial production based on biotechnology Four strategic themes Protein products and production technologies Bio-IT Chemicals and fuels Biosynthetic materials 03/06/2016 11 Living Factories Synbio-PPP Powerhouse Enablers Mapping of IPR & commercial potential Computer-aided designs of enzymes Synthetic production organisms Products and applications Production concepts 03/06/2016 Genome editing tools Useful products from organic wastestreams Wider variety of enzymatic reactions Production organisms designed with mathematical cell models Bioethanol with modified yeast Synthetic production organisms reduce number of unit operations Now All industrial sidestreams exploited Cost-efficient utilization of single carbon (C1) raw materials Biotechnical valorization of Lignin Higher yield enzymes General attitude and approval Wide industrial use of enzymes and on-demand enzyme synthesis Synthetic enzymes that utilize C1 Synthetic yeast Cell switches for synthesis timing Fotosynthesis efficiency improved remarkably From virtual models to automated cell & molecular synthesis New bio composites Materials and made with synthetic cell parts for 3D printing cells Living Animal Smart materials materials Aromates produced proteins from based on biological Biohydrogen biotechnically microbes functionality Non-oil base chemicals in production Pharma molecules with synthetic Biogames enzymes Science based entrepreneurism Open Enabling innovation regulation Therapeutic human proteins from microbes Cell level modeling in process design Mid-term Novel type of economical process enabled by synbio New solutions for storing energy Biotechnology used widely accross indistry sectors Long term 12 VISION With synthetic Biology towards sustainable bioeconomy Majority of industrial production based on biotechnology Tailored enzymes Networked company Synbio-infrastructure ecosystem from lab to pilot High value products from biomass sugars Raw materials ”BioSlush” Living Factories We need a common will 1. To develop production pathways for higher value products, e.g. more valuable composites and biochemicals based on the needs of companies marketing the end-products. 2. To develop synthetic biology technologies that enable the production of new products, the utilization of a larger variety of raw materials, and large and small scale production. Research institutes, universities and public financiers must guarantee the continuation of high-quality synthetic biology applied research in Finland. 3. To establish a PPP working group, Synbio Powerhouse. 03/06/2016 13 Living Factories Synbio Powerhouse Industry Academia Investors IBC Start-ups Other stakeholders Mission: to coordinate the industry-academia collaboration, the development of the synbio start-up culture and the providing of expert advise and consultation to different stakeholders. 03/06/2016 14 Living Factories The real breakthroughs of synthetic biology will be made in the industry, not in research. - Greg Venter 03/06/2016 15 Living Factories 03/06/2016 16 1 12.4.2016 Esa Aittomäki Megatrends and drivers Value chain creation Role of synthetic biology 2 Esa Aittomäki 2.6.2016 Megatrends in biobased industry development CO2 emissions, global warming → governmental mandates Independence from fossil raw material, use of renewable sources Sustainability: reduction of carbon and water foot print, step out from food chain, looking for biobased products and biodegradable plastics Brand owners’ image: Coca Cola, Danone, IKEA, LEGO, L'Oréal,… 3 Esa Aittomäki 2.6.2016 Drivers to biobased industry 4 Esa Aittomäki 2.6.2016 Drivers to biobased industry Producers, developers Technology developers End users, brand owners 5 Esa Aittomäki 2.6.2016 Value creation Grass Intermediates Biogas Products Energy Ethanol, butanol Fuels Triglycerides Grain Amino acids Biochemical Pulp SCP Food, feed Acids Surface active c. Diacids Pharma, cosmetics Cane Fractionation Oil seeds Thermochemical Sorbitol, xylitol Lignocellulose fractionation Straw Lubricants Modified starch Solvents FDCA Chemicals 3-HPA Forest PDO, BDO Emulsifiers Thermal (pyrolysis) 3-HBL Glycerol Pulp mills Biopolymers Resins, glues Furfural Gasification/combustion Modified polymers Lignin Waxes 6 Esa Aittomäki 2.6.2016 BTX chemicals Biorefinery value chain development – biotechnology as an enabler Primary raw material Conversion step 1 Primary intermediate Conversion step 2 Intermediate Final product Formulation Semi final product Conversion step 3 BC 7 Biochemical route Esa Aittomäki C Chemical route 2.6.2016 What’s going on in biobased chemicals IEA 2010 Succinic acid DOE 2015 TOP 12 BC DOE 2016 Near term chemicals 1,4-diacids (succinic, fumaric, malic) BC Butadiene (1,3-) BC C Butanediol (1,4-) BC Ethyl lactate BC BC Furanics C FDCA (2,5-furan dicarboxylic acid) Hydroxypropionic acid/aldehyde BC 3-HPA (3-hydroxypropionic acid) Glycerol derivatives C Levulinic acid C Fatty alcohols Sorbitol C Glycerol C Furfural C Xylitol C Glucaric acid BC Glycerin C Levulinic acid C Aspartic acid BC Isoprene BC BC Lactic acid BC C Propanediol (1,3-) BC C Propylene glycol Biohydrocarbons BC 3-hydroxybutyrolactone Lactic acid BC Sorbitol Ethanol BC Xylitol BC BC BC Glutamic acid BC Succinic acid Itaconic acid BC Xylene BC Biochemical route C Chemical route http://www.nrel.gov/docs/fy16osti/65509.pdf http://www.ieabioenergy.com/wp-content/uploads/2013/10/Task-42-Biobased-Chemicals-value-added-products-frombiorefineries.pdf http://www.biofuelsdigest.com/bdigest/2015/04/30/the-does-12-top-biobased-molecules-what-became-of-them/ 8 Esa Aittomäki 2.6.2016 C BC C Techno economic hurdles Poor feasibility of process concept, value of products and by-products; need to valorize side-streams Availability of raw material and price Technology: low yields, energy intensive, dilute solutions, cost of product recovery 9 Esa Aittomäki 2.6.2016 Finnish economical environment Industry already uses biotechnology: food, feed, chemicals, pulp & paper, energy Extended raw material sourcing: forest based underutilized streams, industrial side streams, C1 compounds (methanol, CO, CO2), agricultural based: straw, grass, manure New bio based products: proteins, polymers, other chemicals, functional food additives and supplements, improved antibioticfree feed New technology platforms: fractionation of lignocelluloses, improved fermentation concepts, product recovery techniques New biocatalyst development: enzymes, whole cells Development of tools for biotechnology to speed-up: SynBio, Bio ICT, speeding-up the microbial strain and protein engineering 10 Esa Aittomäki 2.6.2016 How to jump over hurdles? Focus on low-cost feedstock Improve yields and catalysts performance Look for more valuable products over the whole concept CO H2 Sugar 11 CO2 CH3OH CH4 New routes Improved yields Better productivities Esa Aittomäki 2.6.2016 Thank you for your attention!