Synthetic Biology: applications the needs of a growing and ageing - PDF document

DSM – key activity areas Health Advanced, cost-effective health and medical innovations, and healthier food and beverages, to meet Synthetic Biology: applications the needs of a growing and ageing global population Emrah Nikerel, Nutrition DSM Biotechnology Center World’s leading producer of vitamins and nutritional ingredients meeting the growing need for more nutritious and more sustainable food and animal feed Materials Enabling lighter, stronger, more advanced and more sustainable performance materials DSM’s 22,000 employees deliver annual net sales of about € 9 billion Challenge the future 1 Slide 2 The DSM Biotechnology Network DSM biotechnology center, Delft Percivia DPP/Biologics Boston, USA DFS/DBC Groningen, NL Delft, NL DNP/Microbia DFS/Diadem, Boston, USA Moscow, RUS DAI-Sinochem Hong Kong, CN DFS/Cultures Logan, USA DNP KAU/Sisseln, CH DFS/Enzymes C5-company DFS/DBC SouthBend, USA BoZ, NL Shanghai, CN DNP DNP/Martek DPP/Biocatalysis Grenzach, GER Columbia, USA Geleen, NL DNP/DFS appl. Belvedere, USA DFS/Cultures Moorebank, AUS Slide 3 Slide 4 Cell as a factory – examples @DSM DSM Biotechnology Center Delft Substrate • Established in 2009 by merging of R&D Departments of DSM A Food Specialties and DSM Anti-Infectives DNA mRNA Protein • Applying biotechnology in products and processes B • Approx. 500 scientists & technicians located in Delft Cell Factory • Serves DSM own products in the food, pharma and white biotechnology. Product Product • Contract development and manufacturing services (DSM BioSolutions) Slide 5 Slide 6

Design Examples of Products Pathway & Strain Analyze produced by Biotechnology Build & Test Metabolic model / knowledge base Product pathway Metabolites • vitamins, pharmaceuticals, chemicals Precursor supply ( e.g. antibiotics, citric acid, arachidonic acid) By-products Proteins NADH NAD ATP ADP Energy supply • Enzymes ( e.g. PreventASe™, Panamore™, S P Redox balance Maxiren™ , Maxilact™,….. Compartments Biomass Transport • Yeast Extracts, cultures e.g.Maxarome™, Delvo - Yog™ Alternative routes Slide 7 Slide 8 Biosuccinium TM succinic acid S. cerevisiae Metabolic Engineering Strategy a Versatile Building Block for Multiple Applications Introduction of red. TCA cycle, glyoxylate shunt and export Net stoichiometry combining 2 pathways: 1.4Glc + 1.2CO2 = 2.4Succ + 2.4ATP Y max = 1.71 mol/mol = 1.12 g/g Alcohol dehydrogenase X From <1 g/L to High product concentrations And many other modifications transporter Slide 9 Slide 10 How Old Is Biotechnology ? What is it all about with Biotechnology A wide ranging scientific field which includes the 10,000 BC manipulation of living organisms that results in new products Domesticat or processes by that cell. ing Crops 6,000 BC Brewing Beer Production hosts Saccharomyces cerevisiae (beer, wine, cheese) Aspergillus niger (citrate) Domesticating Animals Clostriduim, Acetobacter (acetone, butanol) 4,000 BC Many, many more 8,000-9,000 BC Leavening Bread Genetic engineering, Metabolic Engineering 1940’s ¡ 1880’s ¡ Synthetic Biology Production of Antibiotics More complex compounds, e.g. including plant pathways Production of Vaccines 1980’s ¡ ¡Use ¡of ¡genetically ¡modified ¡ 11 12 Challenge the future Challenge the future organisms

How Old is Modern Biotechnology? Discovered the Laws Governing the Genetic Inheritance of Traits by Scientific Experimentation Founded Modern Genetics Challenge the future 13 Challenge the future 14 Modern Biotechnology • Molecular Biology - microbiology - biochemistry - cell biology • Molecular Genetics • Genetic Engineering: Moving a gene from one organism to another - chemical engineering - biomanufacturing Challenge the future 15 Challenge the future 16 Slide Drew Endy And what about Biotech apps ? Most projects are Herculean. • If you were to build an iPhone using components from ¡the ¡mid ¡1980s… • Battery 5 times as large • Antenna sticking out • GPS receiver hefty backpack and batteries • Motion sensor was mechanical • Two ¡film ¡camera’s • Processor match Cray X-MP 17 18 Challenge the future Challenge the future

Slide Drew Endy We need new tools. SB Technology drivers Purification and use of EcoRI restriction endonuclease … After converting the Bst EII site into an Bam HI site … the fragment was inserted into the unique BamHI site … the amplified product was cleaved with Spe I and Hind III… Much of rDNA basics unchanged past 30+ years Challenge the future 19 Challenge the future 20 Challenge the future 21 Challenge the future 22 Key concepts in Synthetic Biology Synthetic biology application examples: iGEM projects • Abstraction, Standardization: allows non-biologists to work with cells. • The availability of the SB technology drives not only academia, industry, but also education, small enterprises, backyard labs etc. • Great example of initiative: parts registry database, iGEM projects. • iGEM: international Genetically Engineered Machine competition: Yearly , student competition students come up with their own ideas, concepts, and realize them over summer 23 24 Challenge the future Challenge the future

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Challenge the future 55 Challenge the future 56 Challenge the future 57 Challenge the future 58 Take home messages • SB applications enabled by technology, is the new era, both in applications, and conceptual thinking. Context project: programming life • It has a quite wide area of application • Has its origins in different areas • Molecular Biology, Microbiology, Metabolic Engineering • Nanotechnology (esp. bottom-up approaches) • Information technology • Engineering • SB is not only for biologists!! 59 60 Challenge the future Challenge the future

Context project: programming life From Synthetic Genome to a Synthetic Cell July 2010 • In biotechnology applications typically, • Full length assembly of a • We manipulate the DNA (genotype), Sep 2011 Mycoplasma genome • We observe the physiological response (phenotype) • Transplantation of genome • Synthetic Cell announced for 2010 Gibson et al. (2008) PNAS 105(51): 20404-20409 • Predicting the phenotype from genotype is a great challenge.  One way to achieve this: whole cell models (simple, yet comprehensive) George Church, Harvard (3/2009) Challenge the future 61 Challenge the future 62 Building virtual whole cells (concept) Building whole cell models • Basic elements in a cell: • DNA, • Protein, ribosome, • Metabolism, • Transporters, • Cellular infrastructure (e.g. lipids) Whole cell model for Mycoplasma genitalium Challenge the future 63 Challenge the future 64 Building a whole-cell from scratch Building a whole-cell from scratch Transporter protein synthesis rate: 𝑙 �� ∙ 𝐸𝑂𝐵 Alternative transporters, have different capacity, or affinity, defined ��,�� by 𝑙 �� or 𝐿 � 𝑇 ��� 𝑤 ���������,�� = 𝑤 ��� ∙ 𝑢𝑠𝑏𝑜𝑡𝑞𝑝𝑠𝑢𝑓𝑠 ∙ ��,�� 𝑇 ��� + 𝐿 � Objective: grow on Substrate available in the environment First thing to do: bring the substrate into the cell 65 66 Challenge the future Challenge the future