Wirtschaftliche / Ökonomische Aspekte der Synthetischen Biologie

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Wirtschaftliche / Ökonomische Aspekte der Synthetischen Biologie acatech Journalistenworkshop Synthetische Biologie Frankfurt 14.-15.10.10 B i otechnology Research A n d BInformation i o t e c h n o l o gy Netwo Research r k AG A n d I n f o r m a t i o n Netwo r k A G Dr. Jürgen Eck Vorstand Forschung & Entwicklung BRAIN Aktiengesellschaft

Knowledge Based Bio-Economy (KBBE): Berlin, 08.09.2010 EvoSolution : for novel BioActives

Thesen Die Synthetische Biologie ist als Disziplin der Biotechnologie eine bedeutende Säule einer wissensbasierten Bioökonomie EvoSolution : for novel BioActives

En Route to the Knowledge Based Bio-Economy (KBBE) Key drivers Underlying fundamental trends Innovation need Margin pressure Raw material pricing Increasing energy prices Increasing demands in emerging markets Globalization Economical drivers Underlying fundamental trends Growing population Aging population New markets Demand for healthy products Societal drivers Sustainability triangle Ecological drivers Underlying fundamental trends Regulation issues Raw material access Disposal of waste Green chemistry EvoSolution : for novel Enzymes and novel BioActives

En Route to the Knowledge Based Bio-Economy (KBBE) Biotechnology will be an important pillar of Europe s economy by 2030, indespensable to sustainable economic growth, employment, energy supply and to maintaining the standard of living. It will be increasingly used in labour-intensive sectors, e.g. industrial processing, pharmaceuticals, agriculture and food. By 2030, the products of white biotechnology and bio-energy will have an estimated one-third share, worth 300bln EUR, of industrial production. En Route to the Knowledge-Based BioEconomy Cologne Paper, May 30, 2007 Hosted by the German Presidency of the Council of the European Union EvoSolution : for novel Enzymes and novel BioActives

En Route to the Knowledge Based Bio-Economy (KBBE) red biotechnology white biotechnology green biotechnology Specialty Chemicals Fine Chemicals/API White Biotechnology affects a wide variety of industries Feed/Food/Agro industry Home and personal-care Bulk Chemicals Polymers BioFuels/BioEnergy EvoSolution : for novel Enzymes and novel BioActives

Strongly growing industrial white biotechnology markets Share of industrial white biotechnology within chemicals industry Bio-dependent sales 2005 vs. 2010 (amounts in billion) 2005 2010 Biofuels 28 72 CAGR 2005-2010 20.8% 7% 10% Plant extracts 20 25 4.6% Pharmaceutical ingredients 10 20 14.9% 93% 90% Industrial "w hite" biotechnology Total chemical industry Bulk/polymers 19 31 10.3% Food/feed ingredients 8 11 6.6% Growth rates Oleochemicals 8 9 2.4% CAGR: 4.0% Enzymes 2 3 8.4% CAGR: 12.6% Others 12 14.9% billion 95 172 1,400 1,700 Total Bio 95 172 12.6% 2005 2010 Industrial "w hite" biotechnology 2005 2010 Total chemical industry 2005 2005-2010 grow th Industrial white biotechnology is rapidly growing and estimated to account for 10% of chemicals sales in 2010 EvoSolution : for novel Enzymes and novel BioActives Source: McKinsey 2008: Industrial Biotechnology a perspective on the industry

Selected Marketed White Biotech Products Product Segment BioProcess Production Market value Volume [t/a] [mill. ] Cyclodextrins Speciality BioCatalysis 5.000 50 Glutamate Food Fermentation 1.500.000 1.800 Lactic acid Food/Textile Fermentation 150.000 270 Phenylalanine Food/API Fermentation 10.000 100 Vitamin B12 Food/Cosmetics Fermentation 20 500 Vitamin C Food/Feed Fermentation 80.000 640 Penicilline API/Feed Fermentation 45.000 13.500 Threonine Feed Fermentation 30.000 180 Lysine Feed Fermentation 700.000 1.400 Enzymes Detergent Fermentation 2.500 500 Acrylamide Base Chem. BioCatalysis 100.000 28 PLA Polymers Fermentation 140.000 315 Sources: BRAIN AG, Schmid (2002); Biehl et al. (2004); www.biotechnologie.de EvoSolution : for novel Enzymes and novel BioActives

En Route to the Knowledge Based Bio-Economy (KBBE) What can Synthetic Biology deliver? Alternative Processes Cost reduction by improved production processes Increase in quality of the product by biotechnological processes Accessing renewable feedstock / new raw materials Sustainable processes New Products True Innovations Growth / Market entry with novel Products with novel Molecules from biotechnological production Enabling new Applications and Concepts in different industries (chemistry, energy, pharma, ) EvoSolution : for novel Enzymes and novel BioActives

Thesen Die Synthetische Biologie ist als Disziplin der Biotechnologie eine bedeutende Säule einer wissensbasierten Bioökonomie Die Synthetische Biologie ist die konsequente Fortentwicklung der Molekularbiologie und des Genetic Engineering EvoSolution : for novel Enzymes and novel BioActives

Economical aspects of Synthetic Biology Classical (Micro)biology Molecular Biology Genetic Engineering Synthetic Biology Wild-type strains Host-strains Minimal Genomes Chassis strains Full-synthetic strains Strain-optimisation by unspecific mutation and selection Heterologous Expression of genes Genetic engineering Host-optimisation by knock-in / knock-out Pathway-engineering Artificial pathways de-novo protein design syntethic: not natural, artificial, contrived, produced by synthesis biology: science of live and living organisms Design and construction of new biological parts, devices, systems and the re-design of existing, natural biological systems for useful purposes. EvoSolution : for novel Enzymes and novel BioActives

Designer Microorganisms Renewable Resources Feedstock & Substrates Designer Bugs Fermentative Production of chemicals specialty / fine / bulk materials / bioplastic energy sources / biofuels Ligninocellulose Whey ultrafiltrate Molasses Crop Silage Starch hydrolysates Sugars Prom enzyme1 enzyme2 enzyme3 enzyme4 Pathway Engineering Engineering of physiological pathways Artificial Synthetic Pathways Multistep-Biotransformation EvoSolution : for novel BioActives

Economical aspects: Improved processes / productivity Substrates + Products + Suplements Energy Biomass Heat Wildtype-strain derived production strains Aim: growth & proliferation redundant metabolic pathways and mobility to react on variable environmental conditions balanced mutation-rates vs. repair-systems to allow evolution highly regulated to assure energy & substrate efficiency for growth overflow metabolism during substrate excess Synthetic Biology derived production strains Aim: bioconversion of substrates minimal metabolic capabilities according stable fermentation conditions repair-systems to maintain stability during fermentation process no product- / feedback-inhibition to assure maximum conversion substrate conc. >> 150 g/ltr product conc. >> 150 g/ltr, ~100% conversion EvoSolution : for novel BioActives

Thesen Die Synthetische Biologie ist als Disziplin der Biotechnologie eine bedeutende Säule einer wissensbasierten Bioökonomie Die Synthetische Biologie ist die konsequente Fortentwicklung der Molekularbiologie und des Genetic Engineering Die Synthetische Biologie hat das Potenzial für ressourcen- und energieeffiziente Produktionsverfahren (nachhaltige Volkswirtschaft) EvoSolution : for novel BioActives

Designer Microorganisms Microbial Production of 1,2 Propanediol EvoSolution : for novel BioActives

Designer Microorganisms Synthetic Biology: Microbial Production of 1,2 Propanediol De-icing formulations Plastics, Polymers (polyester resin) crude Glycerin Cooling fluid (engines) Latex paints Heat carrier fluids Liquid cleansers H 3 C Lubricants Plasticizer Concret grinding additive Pharma, Body Care, Cosmetics H 3 C 1,2 Propanediol EvoSolution : for novel BioActives

Designer Microorganisms Synthetic Biology: Microbial Production of 1,2 Propanediol E. coli K12 glda non regulated episomal bypass Gly-3-P glpk Acetol 1,2-PD dhak Citrobacter freundii DH5α::araB::glpK pdp_gdf GAP DHAP mgsa MG Methylglyoxal H 3 C H 3 C O O 2--propaldehyd fuco H 3 C Metagenome screening & Engineering H 3 C 1,2-PD Artificial operon: mgsa glda dhak fuco Methylglyoxalsynthase Glycerindehydrogenase Dihydroxyacetonkinase 1,2-Propandiol- Oxidoreductase EvoSolution : for novel BioActives

Designer Microorganisms Synthetic Biology: Microbial Production of 1,2 Propanediol glda dhak GAP PEP Gly-3-P DHAP NADH2 alda mgsa Inactivation of competing Pathways MG gloa Lactoyl-GSH glob yeig fehlt H 3 C H 3 C Glyoxylase III Acetol O Lactaldehyde O alda NADH2 fehlt fuco H 3 C H 3 C Pyruvat ldha D-Lactat lldd L-Lactat Competing reactions and their key enzymes: alda Aldehyd Dehydrogenase A gloa Glyoxylase I glob Glyoxylase II ldha D-Lactat Dehydrogenase lldd L-Lactat Dehydrogenase EvoSolution : for novel BioActives

Thesen Die Synthetische Biologie ist als Disziplin der Biotechnologie eine bedeutende Säule einer wissensbasierten Bioökonomie Die Synthetische Biologie ist die konsequente Fortentwicklung der Molekularbiologie und des Genetic Engineering Die Synthetische Biologie hat das Potenzial für ressourcen- und energieeffiziente Produktionsverfahren (nachhaltige Volkswirtschaft) Die Synthetische Biologie hat das Potenzial zur Erschließung neuer Rohstoffe und zur Herstellung neuer Produkte (wachsende Volkswirtschaft) EvoSolution : for novel BioActives

Designer En route to the Mikroorganismen Knowledge-based BioEconomy (KBBE) Niederaußem EvoSolution : for novel BioActives

Biosynthetic creativity: the Acidianus ambivalens example A fully integrated nanoscale chemical plant Acidianus ambivalens Metabolism facts Chemo-litho-auto-troph-ic Metabolism T opt 80 C; ph opt 2,5 Sulfur metabolism as sole energy source alternative anaerobic or aerobic metabolism e--donators: H 2, S, e--acceptors: O 2, S Photo: W. Zillig 1 µm fully autotrophic: CO 2 fixation as sole carbon source for all syntheses collaborative genome project BRAIN AG, TU Darmstadt Zentrum für molekulare Evolution und Biodiversität Max Planck Institut für Biochemie, Universität Tübingen EvoSolution : for novel Enzymes and novel BioActives

En route to the Knowledge-based BioEconomy (KBBE) Designer Microorganisms: CO 2 to Plastics Copyright 2010 BRAIN AG, All Rights Reserved EvoSolution : for novel BioActives

Designer Mikroorganismen EvoSolution : for novel BioActives

En route to the Knowledge-based BioEconomy (KBBE) Outlook: Biosynthetic creativity... BACTERIA ARCHAEA EUCARYA Barns et al. (1996) PNAS 93, 9188-9193 Copyright 2010 BRAIN AG, All Rights Reserved EvoSolution : for novel BioActives 1 change / 10 nt

En route to the Knowledge-based BioEconomy (KBBE) Outlook: Biosynthetic creativity expanded by Synthetic Biology BACTERIA ARCHAEA Synthetic Microorganisms based on bacterial chassis Producer X-1 Producer X-2 Producer X-3 Producer X-4 Synthetic Microorganisms without natural ancestor Producer X-1 Producer X-2 Producer X-3 Producer X-4 EUCARYA Barns et al. (1996) PNAS 93, 9188-9193, modified Copyright 2010 BRAIN AG, All Rights Reserved EvoSolution : for novel BioActives 1 change / 10 nt

Thesen Die Synthetische Biologie ist als Disziplin der Biotechnologie eine bedeutende Säule einer wissensbasierten Bioökonomie Die Synthetische Biologie ist die konsequente Fortentwicklung der Molekularbiologie und des Genetic Engineering Die Synthetische Biologie hat das Potenzial für ressourcen- und energieeffiziente Produktionsverfahren (nachhaltige Volkswirtschaft) Die Synthetische Biologie hat das Potenzial zur Erschließung neuer Rohstoffe und zur Herstellung neuer Produkte (wachsende Volkswirtschaft) EvoSolution : for novel BioActives

Thank you for your attention! Dr. Jürgen Eck je@brain-biotech.de BRAIN AG www.brain-biotech.de EvoSolution : for novel Enzymes and novel BioActives