Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications.

[1]  A. Matin,et al.  Analysis of Novel Soluble Chromate and Uranyl Reductases and Generation of an Improved Enzyme by Directed Evolution , 2006, Applied and Environmental Microbiology.

[2]  Olaf Kruse,et al.  Microalgal hydrogen production. , 2010, Current opinion in biotechnology.

[3]  Benjamin Stark,et al.  Use of Genetically Engineered Microorganisms (GEMs) for the Bioremediation of Contaminants , 2006, Critical reviews in biotechnology.

[4]  J. Liao,et al.  Driving Forces Enable High-Titer Anaerobic 1-Butanol Synthesis in Escherichia coli , 2011, Applied and Environmental Microbiology.

[5]  T. Hökfelt,et al.  Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Iris Hunger,et al.  Dual-Use Research and Technological Diffusion: Reconsidering the Bioterrorism Threat Spectrum , 2011, PLoS pathogens.

[7]  Timothy S. Ham,et al.  Production of the antimalarial drug precursor artemisinic acid in engineered yeast , 2006, Nature.

[8]  P. Baker Biofuels: Environmental Consequences and Interactions with Changing Land Use. Comments on the SCOPE report. , 2010 .

[9]  Roberto Cattaneo,et al.  Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded , 2008, Nature Reviews Microbiology.

[10]  Theo M Bestebroer,et al.  Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets , 2012, Science.

[11]  Gregory R. Hagen,et al.  Synthetic biology confronts publics and policy makers: challenges for communication, regulation and commercialization. , 2012, Trends in biotechnology.

[12]  George M. Church,et al.  A new dawn for industrial photosynthesis , 2011, Photosynthesis Research.

[13]  Drew Endy,et al.  Synthetic genomics | options for governance. , 2007, Biosecurity and bioterrorism : biodefense strategy, practice, and science.

[14]  Heather M. Leslie,et al.  Chapter 7: Biodiversity Consequences of Increased Biofuel Production , 2009 .

[15]  Lutz Wobbe,et al.  Improvement of light to biomass conversion by de-regulation of light-harvesting protein translation in Chlamydomonas reinhardtii. , 2009, Journal of biotechnology.

[16]  Hervé C Bossin,et al.  Transgenic mosquitoes and the fight against malaria: managing technology push in a turbulent GMO world. , 2007, The American journal of tropical medicine and hygiene.

[17]  David Rejeski,et al.  Synthetic biology: Four steps to avoid a synthetic-biology disaster , 2012, Nature.

[18]  J. Tait,et al.  Ethical Framework for Biofuels , 2011, Science.

[19]  V. Lorenzo,et al.  Engineering a mouse metallothionein on the cell surface of Ralstonia eutropha CH34 for immobilization of heavy metals in soil , 2000, Nature Biotechnology.

[20]  Stanley N Cohen,et al.  Inhibition of HIV budding by a genetically selected cyclic peptide targeting the Gag-TSG101 interaction. , 2008, ACS chemical biology.

[21]  Michael Berg,et al.  Bacterial bioassay for rapid and accurate analysis of arsenic in highly variable groundwater samples. , 2005, Environmental science & technology.

[22]  Martin Kumar Patel,et al.  Comparing the Land Requirements, Energy Savings, and Greenhouse Gas Emissions Reduction of Biobased Polymers and Bioenergy , 2003 .

[23]  S. Vanneste,et al.  Patent pools and clearinghouses in the life sciences , 2011, Trends in Biotechnology.

[24]  Li Jin,et al.  Female-specific flightless phenotype for mosquito control , 2010, Proceedings of the National Academy of Sciences.

[25]  Martin Fussenegger,et al.  Self-sufficient control of urate homeostasis in mice by a synthetic circuit , 2010, Nature Biotechnology.

[26]  D. Kirn,et al.  Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer , 2009, Nature Reviews Cancer.

[27]  Kwang Myung Cho,et al.  Integrated Electromicrobial Conversion of CO2 to Higher Alcohols , 2012, Science.

[28]  S T E V E N R I P P,et al.  Controlled Field Release of a Bioluminescent Genetically Engineered Microorganism for Bioremediation Process Monitoring and Control , 2000 .

[29]  Steven Ripp,et al.  Controlled Field Release of a Bioluminescent Genetically Engineered Microorganism for Bioremediation Process Monitoring and Control , 2000 .

[30]  James C. Liao,et al.  Metabolic Engineering of Clostridium cellulolyticum for Production of Isobutanol from Cellulose , 2011, Applied and Environmental Microbiology.

[31]  Thomas H Segall-Shapiro,et al.  Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome , 2010, Science.

[32]  Stephen Colagiuri,et al.  Grand challenges in chronic non-communicable diseases , 2007, Nature.

[33]  A. McDowall,et al.  Engineering photosynthetic light capture: impacts on improved solar energy to biomass conversion. , 2007, Plant biotechnology journal.

[34]  S. Atsumi,et al.  Alternative biofuel production in non-natural hosts. , 2012, Current opinion in biotechnology.

[35]  Chris Somerville,et al.  Feedstocks for Lignocellulosic Biofuels , 2010, Science.

[36]  Christopher A. Voigt,et al.  Environmentally controlled invasion of cancer cells by engineered bacteria. , 2006, Journal of molecular biology.

[37]  D. Tilman,et al.  Carbon-Negative Biofuels from Low-Input High-Diversity Grassland Biomass , 2006, Science.

[38]  David E. Swayne,et al.  Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus , 2005, Science.

[39]  Teresa M. Mata,et al.  Microalgae for biodiesel production and other applications: A review , 2010 .

[40]  S. Polasky,et al.  Land Clearing and the Biofuel Carbon Debt , 2008, Science.

[41]  R. Shprintzen,et al.  What's in a name? , 1990, The Cleft palate journal.

[42]  J. Liao,et al.  METABOLIC ENGINEERING OF CLOSTRIDIUM CELLULOLYTICUM FOR 1 ISOBUTANOL PRODUCTION FROM CELLULOSE 2 3 4 , 2011 .

[43]  Vishvanath Nene,et al.  Faculty Opinions recommendation of Live attenuated influenza virus vaccines by computer-aided rational design. , 2010 .

[44]  Blake A. Simmons,et al.  Synthesis of three advanced biofuels from ionic liquid-pretreated switchgrass using engineered Escherichia coli , 2011, Proceedings of the National Academy of Sciences.

[45]  A. Rai,et al.  Synthetic Biology: The Intellectual Property Puzzle , 2007 .

[46]  H. Neumann,et al.  Synthetic biology approaches in drug discovery and pharmaceutical biotechnology , 2010, Applied Microbiology and Biotechnology.

[47]  Robert M. Dirks,et al.  Selective cell death mediated by small conditional RNAs , 2010, Proceedings of the National Academy of Sciences.

[48]  Timothy S. Ham,et al.  Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels. , 2008, Current opinion in biotechnology.

[49]  J. Keasling,et al.  Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids , 2012, Nature Biotechnology.

[50]  Antoine Danchin,et al.  Synthetic biology: discovering new worlds and new words , 2008, EMBO reports.

[51]  Joy Sinha,et al.  Reprogramming Bacteria to Seek and Destroy a Herbicide , 2010, Nature chemical biology.

[52]  C. Donnelly,et al.  Field performance of engineered male mosquitoes , 2011, Nature Biotechnology.

[53]  S. Benkovic,et al.  Production of cyclic peptides and proteins in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Korneel Rabaey,et al.  Metabolic and practical considerations on microbial electrosynthesis. , 2011, Current opinion in biotechnology.

[55]  Jens Nielsen,et al.  Synergies between synthetic biology and metabolic engineering , 2011, Nature Biotechnology.

[56]  Olaf Kruse,et al.  An economic and technical evaluation of microalgal biofuels , 2010, Nature Biotechnology.

[57]  L. Looger,et al.  Computational design of receptor and sensor proteins with novel functions , 2003, Nature.

[58]  J. Toulmé,et al.  Hexitol nucleic acid-containing aptamers are efficient ligands of HIV-1 TAR RNA. , 2005, Biochemistry.

[59]  Jean Paul Metzger,et al.  The Brazilian Atlantic Forest: How much is left, and how is the remaining forest distributed? Implications for conservation , 2009 .

[60]  Markus Schmidt,et al.  Xenobiology: A new form of life as the ultimate biosafety tool , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[61]  J. Ramos,et al.  Laboratory research aimed at closing the gaps in microbial bioremediation. , 2011, Trends in biotechnology.

[62]  Michaelangelo D. Tabone,et al.  Sustainability metrics: life cycle assessment and green design in polymers. , 2010, Environmental science & technology.

[63]  J. Boldt,et al.  Newtons of the leaves of grass , 2008, Nature Biotechnology.

[64]  A. Arundel,et al.  The Bioeconomy to 2030 , 2009 .

[65]  Anoop Singh,et al.  Renewable fuels from algae: an answer to debatable land based fuels. , 2011, Bioresource technology.

[66]  Philippe Marliere,et al.  The farther, the safer: a manifesto for securely navigating synthetic species away from the old living world , 2009, Systems and Synthetic Biology.

[67]  David R Corey,et al.  Novel antisense and peptide nucleic acid strategies for controlling gene expression. , 2002, Biochemistry.

[68]  M. Iadarola,et al.  Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease , 2010, Clinical and Vaccine Immunology.

[69]  E. Wimmer,et al.  Synthetic viruses: a new opportunity to understand and prevent viral disease , 2009, Nature Biotechnology.

[70]  Vincenzo Piemonte,et al.  Land‐use change emissions: How green are the bioplastics? , 2011 .

[71]  P A Singer,et al.  Grand Challenges in Global Health , 2003, Science.

[72]  Ahmad S. Khalil,et al.  Synthetic biology: applications come of age , 2010, Nature Reviews Genetics.

[73]  R. Naidu,et al.  Bioremediation approaches for organic pollutants: a critical perspective. , 2011, Environment international.

[74]  발레 페르난도,et al.  Process for the biological production of 1,3-propanediol with high yield , 2003 .

[75]  Víctor de Lorenzo,et al.  Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology , 2012, FEBS Letters.

[76]  R. Wijffels,et al.  An Outlook on Microalgal Biofuels , 2010, Science.

[77]  A. Newton,et al.  Role of SulP, a nuclear-encoded chloroplast sulfate permease, in sulfate transport and H2evolution in Chlamydomonas reinhardtii , 2005, Photosynthesis Research.

[78]  J. Regalbuto Cellulosic Biofuels—Got Gasoline? , 2009, Science.

[79]  M. Fussenegger,et al.  A synthetic mammalian gene circuit reveals antituberculosis compounds , 2008, Proceedings of the National Academy of Sciences of the United States of America.

[80]  A. Faaij,et al.  Bioenergy revisited: Key factors in global potentials of bioenergy , 2010 .

[81]  J. Wengel,et al.  Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications , 2010, Chemistry & biodiversity.

[82]  F. McCormick,et al.  Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents. , 2002, Cancer cell.

[83]  Aaron Fenster,et al.  Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans , 2011, Nature.

[84]  B. Rutz Synthetic biology and patents , 2009, EMBO reports.

[85]  Jacinto F. Fabiosa,et al.  Use of U.S. Croplands for Biofuels Increases Greenhouse Gases Through Emissions from Land-Use Change , 2008, Science.

[86]  Ivan Razinkov,et al.  Sensing array of radically coupled genetic biopixels , 2011, Nature.

[87]  Y. Chisti Biodiesel from microalgae. , 2007, Biotechnology advances.

[88]  Michelle C. Y. Chang,et al.  Enzyme mechanism as a kinetic control element for designing synthetic biofuel pathways. , 2011, Nature chemical biology.

[89]  K. Shanmugam,et al.  Fermentation of 10% (w/v) Sugar to D(−)-Lactate by Engineered Escherichia coli B , 2005, Biotechnology Letters.

[90]  M. Somleva,et al.  Production of polyhydroxybutyrate in switchgrass, a value-added co-product in an important lignocellulosic biomass crop. , 2008, Plant biotechnology journal.

[91]  Richard Van Noorden Demand for malaria drug soars , 2010, Nature.

[92]  Shuanglin Xiang,et al.  Short hairpin RNA–expressing bacteria elicit RNA interference in mammals , 2006, Nature Biotechnology.

[93]  Daniel C. Ducat,et al.  Rewiring hydrogenase-dependent redox circuits in cyanobacteria , 2011, Proceedings of the National Academy of Sciences.

[94]  K. Timmis,et al.  Assemblage of ortho cleavage route for simultaneous degradation of chloro- and methylaromatics. , 1987, Science.

[95]  James C Liao,et al.  Metabolic engineering of cyanobacteria for 1-butanol production from carbon dioxide. , 2011, Metabolic engineering.

[96]  A. Bondeau,et al.  Indirect land-use changes can overcome carbon savings from biofuels in Brazil , 2010, Proceedings of the National Academy of Sciences.

[97]  John C. Chaput,et al.  Synthetic Genetic Polymers Capable of Heredity and Evolution , 2012, Science.

[98]  E. Va,et al.  Changes in soil organic carbon under biofuel crops , 2009 .

[99]  C. Lartigue,et al.  Synthetic genomics: potential and limitations. , 2012, Current opinion in biotechnology.

[100]  T. Anchordoquy,et al.  Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics. , 2011, Journal of pharmaceutical sciences.

[101]  F. Collins,et al.  Benefits and Risks of Influenza Research: Lessons Learned , 2012, Science.

[102]  J. Melillo,et al.  Indirect Emissions from Biofuels: How Important? , 2009, Science.

[103]  Keith E. J. Tyo,et al.  Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli , 2010, Science.

[104]  H. Schallig,et al.  The world of artemisia in 44 questions. , 2006 .

[105]  Xinyao Liu,et al.  Fatty acid production in genetically modified cyanobacteria , 2011, Proceedings of the National Academy of Sciences.

[106]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[107]  A. Burgard,et al.  Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. , 2011, Nature chemical biology.

[108]  J. Liao,et al.  Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels , 2008, Nature.

[109]  Christina D Smolke,et al.  Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins , 2010, Science.

[110]  J. Keasling,et al.  Engineering a mevalonate pathway in Escherichia coli for production of terpenoids , 2003, Nature Biotechnology.

[111]  G. Boulianne,et al.  Green fluorescent protein as a vital marker and reporter of gene expression in Drosophila. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[112]  S. Belkin,et al.  Where microbiology meets microengineering: design and applications of reporter bacteria , 2010, Nature Reviews Microbiology.

[113]  V. de Lorenzo,et al.  Metabolic engineering of bacteria for environmental applications: construction of Pseudomonas strains for biodegradation of 2-chlorotoluene. , 2001, Journal of biotechnology.

[114]  A. James,et al.  Genetic elimination of dengue vector mosquitoes , 2011, Proceedings of the National Academy of Sciences.

[115]  Mark Harvey,et al.  The new competition for land: Food, energy, and climate change , 2011 .

[116]  Andrea Crisanti,et al.  A synthetic homing endonuclease-based gene drive system in the human malaria mosquito , 2011, Nature.

[117]  C. Khosla,et al.  A Balancing Act for Taxol Precursor Pathways in E. coli , 2010, Science.

[118]  Brent Erickson,et al.  Synthetic Biology: Regulating Industry Uses of New Biotechnologies , 2011, Science.

[119]  R. Johnston,et al.  Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice , 2008, Proceedings of the National Academy of Sciences.

[120]  R. H. Williams,et al.  The contribution of biomass in the future global energy supply : a review of 17 studies , 2003 .

[121]  Jay Shankar Singh,et al.  Genetically engineered bacteria: an emerging tool for environmental remediation and future research perspectives. , 2011, Gene.

[122]  Víctor De Lorenzo,et al.  Tracing explosives in soil with transcriptional regulators of Pseudomonas putida evolved for responding to nitrotoluenes , 2008, Microbial biotechnology.

[123]  N. Forbes Engineering the perfect (bacterial) cancer therapy , 2010, Nature Reviews Cancer.

[124]  Jian Yu,et al.  The greenhouse gas emissions and fossil energy requirement of bioplastics from cradle to gate of a biomass refinery. , 2008, Environmental science & technology.

[125]  J. Keasling,et al.  Microbial production of fatty-acid-derived fuels and chemicals from plant biomass , 2010, Nature.

[126]  James C Liao,et al.  Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde , 2009, Nature Biotechnology.

[127]  J. Bryk,et al.  Scientific Standards and the Regulation of Genetically Modified Insects , 2012, PLoS neglected tropical diseases.