DANSK BIOTEK medlemsmøde 3. oktober 2013

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1 DANSK BIOTEK medlemsmøde 3. oktober 2013 Industriel bioteknologi i Danmark Novo Nordisk Foundation Center for Biosustainability, Kogle Allé 6, 2970 Hørsholm Program: Registrering og networking Velkomst ved Martin Bonde, Formand for DANSK BIOTEK Future Cell factories ved Bernhard Palsson, CEO, Novo Nordisk Foundation Center for Biosustainability Dansk biomasse til industriel anvendelse, potentiale og barrierer ved Claus Felby KU Life Maabjerg Energy Concept verdens mest avancerede bioraffinaderi? ved Jørgen Udby, bestyrelsesformand for Maabjerg Energy Concept I/S Etablering af EU baseret Offentligt-Privat-Partnerskab for industriel bioteknologi ved Lars Christian Hansen, Novozymes Afslutning ved Martin Bonde DANSK BIOTEK og Novo Nordisk Foundation Center for Biosustainability byder på en lille forfriskning

2 Velkommen til DANSK BIOTEKS medlemsmøde om Industriel Bioteknologi

3 Program Registrering og networking Velkomst ved Martin Bonde, Formand for DANSK BIOTEK Future Cell factories - Bernhard Palsson, CEO, Novo Nordisk Foundation Center for Biosustainability Dansk biomasse til industriel anvendelse, potentiale og barrierer ved Claus Felby KU Life Maabjerg Energy Concept verdens mest avancerede bioraffinaderi? ved Jørgen Udby, bestyrelsesformand for Maabjerg Energy Concept I/S Etablering af EU baseret Offentligt-Privat-Partnerskab for industriel bioteknologi ved Lars Christian Hansen, Novozymes Afslutning ved Martin Bonde DANSK BIOTEK og Novo Nordisk Foundation Center for Biosustainability byder på en lille forfriskning

4 TAK til Novo Nordisk Foundation Center for Biosustainability

5 Vil tøbrud i USA smitte af på Danmark? USA Oktober biotekvirksomheder børsnoteret i biotekvirksomheder har i 2013 rejst omkring 2,2 milliarder USD 10 virksomheder mere på vej til notering Danmark oktober 2013 Biogen Idec i gang med at producere sklerosemidlet Tysabri Nyheder fra Genmab, Zealand og Santaris om milepælsbetalinger og nye eller udvidede samarbejder REBBLS etableret, Rising Entrepreneurs in BioBusiness and Life Science

6 Dårligt signal i Finanslov for mia. afsat til forskning sidste år beskæres i det til 20,8 mia. kr. Højteknologifonden mister 45 mio. kr. sammenlignet med sidste år Faldende bevillinger på flere områder inden for forskning og innovation Den offentlige forsknings andel af BNP falder fra 1,12 til 1,09% i 2014 for at komme helt ned på 1.0% i

7 Integrated large-scale biomass supply: The Danish + 10 mio tonnes study Dansk biomasse til industriel anvendelse, potentiale og barrierer Uffe Jørgensen, University of Aarhus Niclas Scott Bentsen, Vivian Kvist Johansen, Morten Gylling and Claus Felby University of Copenhagen

8 We can make anything from plants Food, feed, fuels, chemicals, materials and CCS Biomass is seen as one of the elements of a future sustainable economy Building a bio-based low carbon economy requires GIGA TONS of biomass This presentation is about how we may approach a sustainable biomass supply using the biology, technology and infrastructure already available

9 in the state of Denmark Renewables accounts for 27% of the energy supply. 66% is from biomass) Current use of biomass 8 mill tons/year (3 mill tons inported) Biomass is planned to take up 20-30% of the total energy supply This will require approx. +10 mio tons of biomass How much of that biomass can we produce ourselves? Waste Straw Wood Biogas

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11 2G biofuels and biorefineries may avoid the food/fuel conflict Skov & Landskab But if we start replacing food and feed crops with energy crops it will basically be the same problem It is a question of land use, as land is the ultimate limiting factor, not XX tons of biomass So. If we put land as the limiting parameter, how should we approach the supply of biomass? Expansion or intensification?

12 Expansion: Feeding 9 bilion people +Meat ++Meat +++Meat ++++Meat +++++Meat Today we grow crops on an area the size of South America

13 Intensification: Increased biomass ressource from the same area? For more than 10,000 years we have optimised our crops for food and feed

14 Intensification but under constraints Existing agriculture and forestry Crops, trees and farming/forestry practice Already established established infrastructure Could danish agriculture and forestry deliver 10 mill tons extra biomass by 2020 under the assumptions of: No reduction in food production No extra land use Reduced environmental impact Sustainable intensification is it a possibility or a pie in the sky?

15 Danish agriculture and forestry No idle land -60% of the area is farm land Current harvest ca. 18 mill t Mainly agriculture 80% is used for animal feed 17 mill tons surplus of manuer Surplus of straw Large import of wood

16 Three scenarios for 2020 Business as usual BAU No change in crops or technology Annual yield increment approx. 1% More collection and use of existing biomass/residues High use of manure Biomass optimized High straw yield cultivars Increased collection of straw and wood Less share of oil crops higher share of energy crops Fertilization of grass in wetlands areas Verges, weeds, secondary crops etc. High use of manure Environmentally optimized No removal of straw in low soil carbon areas Maximum use of secondary and energy crops No cereals in areas with high nitrate leaching Increased forestation High use of manure

17 Data for calculations and scenarios Productivity: The general agricultural register (GLR), the central livestock register (CHR), StatBank Denmark National Forest Inventory Geographical data: DJF geodata, Fertiliser accounts, GIS maps of roads, watercourses, urban and wooded areas, Digital field maps, Nitrogen leaching maps Soil carbon maps

18 Better solar energy capture: Potential yield increments Current yield of wheat 9 t/ha Current yield of corn 12 t t/ha Potential yield of corn + winter rye 18 t/ha Potential yield of beet 26 t/ha Potential yield of Miscanthus : 20 t/ha Make use of the whole growth season C 4 Photosynthesis

19 + 10 mio tonnes is possible! BAU can deliver +4 mio tonnes Achieved by: Existing technology and existing crops and trees Use of the full growth season Intermediate crops High biomass yield varities Higher share of perennial crops Can we mantain food production? Environmental impact?

20 Can food/feed production be mantained? Loss of area for food crops approximately 200,000 ha (7%) Yield increment and more efficient production can not make up for the full loss High feed value carbohydrates and proteins are present in the biomass Biorefinery feed products are important Development of separation technologies are important Always conserve protein!

21 Environment: Areas with low nitrate retention change to perennial crops tons N

22 Copenhagen Plant Science Centre Building investments: Approx 400 mio DKK

23 Visions Create new knowledge on complex functions of plants - as individual organisms and in crop populations Use synthetic biology to exploit plant systems diversity and identify, characterize and reassembly Gain fundamental knowledge that can be exploited in molecular breeding to develop crops with stable or increased yields under adverse growth conditions Increase the yield and sustainability of plant production by optimizing resource use efficiency and population performance. CPSC director Dr. Dario Leister

24 Technology backend Biomass from many sources. Technology must handle: Low to high salt levels Low to high protein content Low to high moisture content Non carbohydrates (lignin) We need technology for processing of lignin Need for separation technologies Processes for upgrading and separation of protein has a high impact on land use efficiency

25 Technology development Metabolic yield vs. process yield Megaton-scale Hydrolysis and anaerobic fermentation are thermodynamically dowhill The lower the energy quality we can use as process energy, the more we can reduce entropy i.e. loss of work Biomass Biochemical processing and separation Sugars, lignin, protein By combined biochemical and thermal processing we may optimize the level of services (work) from the biomass Fermentation Thermal reforming

26 Conclusions and perspective We have only presented scearios! It is possible to boost biomass production in intensive modern agricilture sustainable intensification Environmental benefits from perennial crops Economy some of the biomass will be to expensive if environemntal benefits are not priced. Job creation. Direct employment jobs A biorefinery sector is important for converting different biomasses and for recovery of protein Looking ahead; using land as the limiting factor and minimising land use will improve sustainability and avoid technology pitfalls We need to focus more on ressource efficiency, optimize use of all biomass components We can make it with existing agriculture and forestry not one extra m 2 of land. Bye, bye ILUC +10 mio tonnes study can be downloaded from

27 Thank you for your attention

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29 Maabjerg Energy Concept 1. Præsentation af MEC konsortiet 2. Grundlæggende om konceptet 3. Råvarer 4. Økonomi 5. Realiseringstidsplan 6. Perspektivering 7. Spørgsmål Ved Bestyrelsesformand Jørgen Udby, MEC I/S

30 Konsortiet Maabjerg Energy Concept I/S Formål: Konsortiets mål er at tilvejebringe et samlet teknisk, juridisk og økonomisk grundlag, for en realiseringsbeslutning. Ejere: Lokalkonsortiet I/S 50 % - Vestforsyning A/S, Struer Forsyning A/S, Nomi I/S Dong Energy A/S og Novozymes A/S 50% Kapital: 55,5 mio. kr. - EUDP har støtte projektet med 10 mio. kr. -Den grønne omstillingsfond har støttet projektet med 5.5 mio. kr. Bestyrelsen: Repræsentanter fra ejerne. Projektorganisation: Egne ressourcer, en række rådgivningsvirksomheder og vidensinstitutioner - tilpasses løbende til opgaverne.

31 IDÉ - Et bioraffinaderi med fokus på energi output Udnyttelse af synergi i ressourceomsætning og procesanlæg Transportbrændstof 34 % (Energi) Biomasse 2. Generation Bioethanol Biogas Maabjerg BioEnergy El & varme 53 % (Energi) Biomasse Kraftvarme Maabjergværket VE - gas 13 % (Energi) Næringsstoffer

32 Teknologiskiftet - Råvarer og deres omsætning t husdyrgødning t biomasseaffald t spildevandsslam Biogas t vinasse 50 mio. m 3 biogas Næringsstoffer N : tons / år P : tons / år K : ton / år t halm 2. G Bioethanol 80 mio. liter bioethanol t lignin t biobrændsel t affald Kraftvarme Varme og el til ca husstande

33 Ressourcestrømme - optimering Opgraderingsanlæg Vindmøllestrøm El Brintproduktion Brint VE- gas Husholdning/Erhverv Dagrenovation Biovæske Affaldsbehandling Faststof (RDF) Genbrug Spildevand Fødevareindustri Slam Restbiomasse Gylle mv. Gødning Biogas Fiber Damp Lignin Biomasse Kraftvarme Biogas Varme Biogas Kraftvarme Varme El Landbrug Halm Vinasse 2. Generation Bioethanol Kølevarme Damp Næringsstoffer Ethanol Transportbrændstof

34 Råvarer Tilstedeværelse af hvede og byghalm Geografi Mio. tons Ikke bjærget I alt Hvede Jylland (inkl. besluttet udfaset) Byg Øvrig DK Danmark

35 Selskabsøkonomiske nøgletal basisberegning Emne Mia. kr. Samlet investeringssum (ny investeringer) 2,2 o Bioethanol 1,8 o kraftvarme 0,3 o Biogas og opgradering 0,1 Finansiering o Egenfinansiering 0,8 o Belåning 1,4 Årlig omsætning (fuld produktion) 1,0 Akkumuleret overskud (efter skat) 2,3 Intern Rente (IRR efter skat) 8,8%

36 Samfundsøkonomiske nøgletal Emne Resultat Beskæftigelseseffekt* o Byggeperiode (fuldtidsjob pr. år i 2 år) o Varigt (fuldtidsjob pr. år) Brutto nationalproduktet (BNP - ADAM grundforløb) o Investeringsperioden (mio. kr.) o Varigt (mio. kr.) Klimaeffekt o CO 2 besparelse (tons / år) Heraf i transportsektoren *Lave tal er beregnet efter ADAM grundforløb

37 Beskæftigelsens sammensætning

38 MEC koncernen i realiseringsfasen DONG A/S Novozymes A/S Struer Forsyning Varme A/S Vestforsyning Varme A/S 49 Evt. øvrige Nøgletal: Aktiver 3.1 mia. kr. Maabjerg Energy Concept MEC Holding A/S Egenkapital 0.6 mia. kr. Omsætning 1.0 mia. kr BioEthanol A/S BioGas A/S (Maabjerg BioEnergy) BioEnergy A/S (Måbjergværket)

39 Rammevilkår MEC`s behov for politiske vilkår: Bæredygtighedskriterier og iblandingskrav MEC`s behov for økonomiske vilkår: Prissikring : 1 kr. liter i 7 år efter NER ( ) Forsikringsordning) Anlægsstøtte : 330 mio. kr. Ansøgt NER støtte på 1 kr. liter i 5 år. Svarer til niveauet i EU`s nye PPP ordning.

40 Projektrealisering Igangsætning 27. aug Konceptvurdering april 2012 Valg af Teknologi & design juli 2013 Realiseringsbeslutning sommer 2014 Investeringsbeslutning sommer 2015 Idriftsættelse sommer 2017 Mobiliserings Analyse fase Mobiliserings- fase 1.1 fase 1.2 Teknologitilpasning Ressourceoptimering Sekundære ressourcestrømme Mobiliserings- fase 2 Anlægs- fase Drift- fase Lignin- og sukkerplatform Rammevilkår

41 Perspektivering Dansk vækstpotentiale Forskning & udvikling Politiske rammevilkår Bæredygtighed Iblandingskrav Prissikring / Støtte F&U midler Uddannelse Forskning Test Demonstration Vidensforankring Mere biomasse 10 mio. tons planen Logistikoptimering Markedsplads Videreudvikle bioteknologier Biogas, Forgasning Lignin- sukkerplatform Nye produkter og markeder Anvendelsesteknologi Afsætningsoptimering Erstatte fossile produkter Danmark som nettoeksportør Produkter, systemer, viden

42 MEC`s bioraffinaderi Maabjerg Bioethanol Maabjerg BioEnergy Måbjergværket

43 BRIDGE Biobased and Renewable Industries for Development and Growth in Europe Realising the biobased economy potential in Europe 3 October 2013 A PUBLIC-PRIVATE PARTNERSHIP ON BIOBASED INDUSTRIES Lars Hansen, Vice President Novozymes

44 Biobased Economy concept

45 What s in it for Europe? Growth A global biobased market estimated at 200 billion by 2020* Jobs Create over 1 million jobs between 2010 and 2030 mainly in rural areas** Energy and Products Energy security Reduce dependence on imports with locally sourced and produced goods and products*** Climate BRIDGE derived biobased products can achieve an average GHG emissions reduction potential of least 50% compared to fossil alternatives**** Sources: * McKinsey / World Economic Forum ** Bloomberg New Energy Finance *** European Commission **** BRIDGE 2020 Strategic Innovation and Research Agenda (SIRA) 3

46 Competing in the global race US About $50 billion invested over the last decade on biofuels and biochemicals. In 2012, President Obama committed to further invest and support the development of the bioeconomy as a major engine for American innovation and economic growth BRAZIL Aims to be N 1 Global Bioeconomy R$ 3,3 billion support for 2 nd generation bioethanol, biochemicals and biomass gasification technologies CHINA $308,5 billion investment on science & technology with biotechnology as a major priority over Substitute 20% of crude oil imports by 2020

47 Policies can make the wheels turn DEMAND DEMAND Incentives for biobased products Public procurement schemes Standards SUPPLY Support biomass development and collection SUPPLY INVESTMENT INVESTMENTS Loans / guarantees First-of-its-kind commercial plants

48 About BRIDGE Biobased and Renewables Industries for Development and Growth in Europe A Public-Private Partnership (PPP) between the Biobased Industries and the EU A joint commitment of 3.8 billion over o o 1 billion (EU) 2.8 billion (Biobased Industries) Multi-annual funding programmes for biobased projects Enabling rural development and re-industrialisation in Europe

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50 Focus Feedstock Fostering a sustainable biomass supply and building new value chains Biorefineries Optimising efficient processing through R&D and upscaling in large-scale demo/flagship biorefineries Markets, products and policies Developing markets for biobased products and optimising policy frameworks

51 Lacking EU support for demonstration International benchmark on the share of basic, applied and development activities 100% 90% 6% 2% 80% 70% 58% 48% 60% 50% 40% 28% FP7 92% Demonstration Applied research Basic research/fp7 30% 20% 10% 32% 11% 24% 0% China US EU Source: Key Science and Engineering Indicators, National Scientific Board, 2010 Digest, NSF, OECD Research & Development Statistics

52 Novozymes is active across the value chain Biobased product value chain Biomass production Biomass conversion Product formulation Enzymatic pesticides Microbial yield enhancers Fertility enhancers Conversion of biomass to sugars Microbiological conversion of sugars to biobased products such as bioethanol, acrylic acid etc.

53 The biobased society and Denmark a perfect match One of the World s strongest food clusters World leading industrial players Strong links to academia Substantial amounts of biomass available Denmark at the forefront in the transformation to a biobased society

54 Investing in new and sustainable ways to organise our economy

55 Cell Factories of Tomorrow The CFB Team

56 The CFB Vision: The Center will facilitate the emergence of the next generation of cell factories. Cell factories will transform the production and manufacture of chemical structures. The Center will lead this transformative development Mission: To determine the range of molecules that can be produced biologically Basic research Shorten the strain design and development process Translational research Innovation through development of new technologies and transfer of knowledge to industry for the benefit of society. Development of talent the future driving force of bio-based sustainability 3 DTU Biosustain, Technical University of Denmark

57 Current organisms Escherichia coli Bakers yeast Fine chemicals, bulk biochemicals, drugs, food ingredients and consumer products In-silico genome scale evaluation and design Pathway exploration and design Chinese Hamster Ovary cells Omics data generation Genetic manipulation Therapeutic proteins Phenotyping 4 DTU Biosustain, Technical University of Denmark

58 FTE's Staff prognosis for CFB Satellites External funding Adm & BD DTU Sections Core Year 9 DTU Biosustain, Technical University of Denmark

59 iloop The organizing paradigm of the CFB

60 Cell factory development loop: concept Model predictions Literature mining Public databases Product Host In silico design and data analysis ics s Systems-level analysis Genome engineering Host genotype Pathway components: Adaptive Laboratory Genes, promoters, Evolution terminators etc Oligos Vectors Screening and physiology 1 8 Fermetation physiology Growth curves High throughput screening data

61 Data generated in the iloop Model predictions Literature mining Public databases In silico design and data analysis Genomics Transcriptomics Proteomics Metabolomics Fluxomics Glycomics Systems-level analysis Genome engineering Host genotype Pathway components: Genes, promoters, terminators etc Oligos Vectors Screening and physiology 1 9 Fermetation physiology Growth curves High throughput screening data

62 Equipment needs for the iloop Equipment Sequencers Mass spectometers (proteomics, metabolomics, glycomics,fluxomics) Data Genomics Transcriptomics Proteomics Metabolomics Fluxomics Glycomics 2 0 Systems-level analysis Equipment FACS and other single cell assays Targeted analytical chemistry Cultivation robotics ALE robotics Plate readers Small/medium-scale fermentation In silico design and data analysis Screening and physiology Genome engineering Data Fermetation physiology Growth curves HT screening data Equipment MAGE robotics Cloning robotics Synthetic gene/ pathway construction Data Host genotype Pathway components: Genes, promoters, terminators etc Oligos Vectors

63 Some technologies being developed for the iloop

64 Adaptive Laboratory Evolution (ALE) Adam Feist

65 ALE Command Center Online Monitoring System Accelerating Decision Making and Troubleshooting Webcam Action Queue Status and Supplies Real time Data 3 0

66 Selecting for improved production traits Morten Sommer

67 3 2 Selecting for optimized cell factories

68 Bioinformatics & Modeling Markus Herrgard

69 3 9 Genome-scale strain design workflows

70 BioProcess and Strain Development

71 3HP Production Irina Borodina

72 Metabolic Engineering of Yeast EasyClone method for iterative chromosomal integration of mutiple genes in S. cerevisiae 5 5

73 µ max (h -1 ) 3-hydroxy propionic acid production in yeast 0.5 Growth of SFA1 allele replacement strains on 3HP no 3HP 10 g/l 3HP 25 g/l 3HP 40 g/l 3HP 50 g/l 3HP SFA1-wt SFA1-evo1 SFA1-evo2 Titer Rate Yield ,68±0,33 g/l 0,24±0,01 g/l/h (FB) 14±0% C-mol/C-mol gluc Jensen et al (2013). Microbial Production of 3- Hydroxypropionic Acid. EPO patent application Borodina et al (2012). Genetically Engineered Yeast. EPO patent application Kildegaard et al (2013). 3HP tolerance. EPO patent application

74 Serine production Alex Toftgaard Nielsen

75 Serine Production in E. coli Pyruvate SerA SerB SerC Glycine Cysteine Feed back inhibition Degradation pathways eliminated Resistance towards serine evolved Production demonstrated during fed batch fermentation 5 8 Hemanshu Mundhada

76 Melatonin production Jiangfeng Zhu

77 Melatonin Pathway (From Mammalian cells) Optimization of TPH expression with a biosensor Identifying 5HTP degradation pathways in E. coli 5HTP production in E. coli 5HTP N-acetylserotonin and melatonin production in S. cerevisiae DTU Biosustain, Technical University of Denmark

78 Flavonoid production Jérôme Maury

79 specific fluorescence (a.u.) Biosensors for flavonoid detection Single cells can be isolated Empty + sensor FLS + sensor 62 DTU Biosustain, Technical University of Denmark

80 Electrosynthesis Karsten Zengler

81 Efficiency 8% Efficiency 90% Store electrical- into chemical-energy Truly a bio-sustainable technology Transformative DTU Biosustain, Technical University of Denmark

82 Improved Production DTU Biosustain, Technical University of Denmark

83 Summary The CFB has been built over the past 2.5 years and should be in its full constellation by the end of 2013 There will be about 200 FTEs associated with it The CFB is focused on genome-scale approach to cell factories design The CFB wants to build new strain design procedure based on an iterative model-guided procedure The CFB is developing a suite of innovative experimental and computational technologies The CFB has picked a few model molecules to work on, but will reexamine this selection with its new econometric unit 71 DTU Biosustain, Technical University of Denmark

84 Acknowledgement The Novo Nordisk Foundation 72 DTU Biosustain, Technical University of Denmark