Synthetic biology

Synthetic biology is an interdisciplinary branch of biology and engineering. The subject combines various disciplines from within these domains, such as biotechnology, evolutionary biology, molecular biology, systems biology, biophysics, computer engineering, and genetic engineering.

Descriptions of synthetic biology depend on how the user approaches it, as a biologist or as an engineer. Originally seen as a subset of biology, in recent years the role of electrical and chemical engineering has become more important. For example, one description designates synthetic biology as "an emerging discipline that uses engineering principles to design and assemble biological components".[1] Another description, by Jan Staman Director of the Rathenau Institute in The Hague in 2006, portrayed it as "a new emerging scientific field where ICT, biotechnology and nanotechnology meet and strengthen each other".[2]

The definition of synthetic biology is debated, not only among natural scientists and engineers but also in the human sciences, arts and politics.[3] One popular definition[4] is "designing and constructing biological modules,[5] biological systems, and biological machines for useful purposes." However, the functional aspects of this definition are rooted in molecular biology and biotechnology.[6]

As usage of the term has expanded to many interdisciplinary fields, synthetic biology has been recently defined as the artificial design and engineering of biological systems and living organisms for purposes of improving applications for industry or biological research.[7]

Synthetic Biology Open Language (SBOL) standard visual symbols for use with BioBricks Standard

History

The first identifiable use of the term "synthetic biology" was in Stéphane Leduc’s publication of « Théorie physico-chimique de la vie et générations spontanées » (1910)[8] and « La Biologie Synthétique » (1912).[9]

Sixty-four years later, in 1974, the term gained its more modern usage when Polish geneticist Wacław Szybalski used the term "synthetic biology",[10] writing:

Let me now comment on the question "what next". Up to now we are working on the descriptive phase of molecular biology. … But the real challenge will start when we enter the synthetic phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with an unlimited expansion potential and hardly any limitations to building "new better control circuits" or ..... finally other "synthetic" organisms, like a "new better mouse". … I am not concerned that we will run out of exciting and novel ideas, … in the synthetic biology, in general.

When in 1978 Arber, Nathans and Smith won the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes, Wacław Szybalski wrote in an editorial comment in the journal Gene:

The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.[11]

A notable advance in synthetic biology occurred in 2000, when two articles in Nature by Michael B. Elowitz and Stanislas Leibler discussed the creation of biological circuit devices of a genetic toggle switch and a biological clock by combining genes within E. coli cells.[12][13]

Perspectives

Engineering

Engineers view biology as a technology – the systems biotechnology or systems biological engineering.[14] Synthetic biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health (see Biomedical Engineering) and our environment.[15]

Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: standardization of biological parts, biomolecular engineering, genome engineering. Biomolecular engineering includes approaches which aim to create a toolkit of functional units that can be introduced to present new technological functions in living cells. Genetic engineering includes approaches to construct synthetic chromosomes for whole or minimal organisms. Biomolecular design refers to the general idea of de novo design and additive combination of biomolecular components. Each of these approaches share a similar task: to develop a more synthetic entity at a higher level of complexity by inventively manipulating a simpler part at the preceding level.[16]

Re-writing

Re-writers are synthetic biologists interested in testing the irreducibility of biological systems. Due to the complexity of natural biological systems, it would be simpler to re-build the natural systems of interest from the ground up; In order to provide engineered surrogates that are easier to comprehend, control and manipulate.[17] Re-writers draw inspiration from refactoring, a process sometimes used to improve computer software.

Key enabling technologies

Several key enabling technologies are critical to the growth of synthetic biology. The key concepts include standardization of biological parts and hierarchical abstraction to permit using those parts in increasingly complex synthetic systems.[18] Achieving this is greatly aided by basic technologies of reading and writing of DNA (sequencing and fabrication), which are improving in price/performance exponentially (Kurzweil 2001). Measurements under a variety of conditions are needed for accurate modeling and computer-aided-design (CAD).

Standardized DNA parts

The most used[19]:22–23 standardized DNA parts are BioBrick plasmids invented by Tom Knight in 2003.[20] Biobricks are stored at the Registry of Standard Biological Parts in Cambridge, Massachusetts and the BioBrick standard has been used by thousands of students worldwide in the international Genetically Engineered Machine (iGEM) competition.[19]:22–23

DNA synthesis

In 2007 it was reported that several companies were offering the synthesis of genetic sequences up to 2000 bp long, for a price of about $1 per base pair and a turnaround time of less than two weeks.[21] Oligonucleotides harvested from a photolithographic or inkjet manufactured DNA chip combined with DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression or incorporate novel amino-acids (see George M. Church's and Anthony Forster's synthetic cell projects.)[22] This favors a synthesis-from-scratch approach.

Additionally, the CRISPR/Cas system has emerged as a promising technique for gene editing. It was hailed by The Washington Post as "the most important innovation in the synthetic biology space in nearly 30 years."[23] While other methods take months or years to edit gene sequences, CRISPR speeds that time up to weeks.[23] However, due to its ease of use and accessibility, it has raised a number of ethical concerns, especially surrounding its use in the biohacking space.[24][25][26]

DNA sequencing

DNA sequencing is determining the order of the nucleotide bases in a molecule of DNA. Synthetic biologists make use of DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide a wealth of information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, synthetic biologists use sequencing to verify that they fabricated their engineered system as intended. Third, fast, cheap and reliable sequencing can also facilitate rapid detection and identification of synthetic systems and organisms.[27]

Modular protein assembly

While DNA is most important for information storage, a large fraction of the cell's activities are carried out by proteins. Therefore, it is important to have tools to send proteins to specific regions of the cell and to link different proteins together, as desired. Ideally the interaction strength between protein partners should be tunable between a lifetime of seconds (desirable for dynamic signaling events) up to an irreversible interaction (desirable when building devices stable over days or resilient to harsh conditions). Interactions such as coiled coils,[28] SH3 domain-peptide binding[29] or SpyTag/SpyCatcher[30] have helped to give such control. In addition it is important to be able to regulate protein-protein interactions in cells, such as with light (using Light-oxygen-voltage-sensing domains) or cell-permeable small molecules by Chemically induced dimerization.[31]

Modeling

Models inform the design of engineered biological systems by allowing synthetic biologists to better predict system behavior prior to fabrication. Synthetic biology will benefit from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Recently, multiscale models of gene regulatory networks have been developed that focus on synthetic biology applications. Simulations have been used that model all biomolecular interactions in transcription, translation, regulation, and induction of gene regulatory networks, guiding the design of synthetic systems.[32]

Research examples

Synthetic DNA

Driven by dramatic decreases in costs of making oligonucleotides ("oligos"), the sizes of DNA constructions from oligos have increased to the genomic level.[33] For example, in 2000, researchers at Washington University reported synthesis of the 9.6 kbp (kilo base pair) Hepatitis C virus genome from chemically synthesized 60 to 80-mers.[34] In 2002 researchers at SUNY Stony Brook succeeded in synthesizing the 7741 base poliovirus genome from its published sequence, producing the second synthetic genome. This took about two years of work.[35] In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks.[36] In 2006, the same team, at the J. Craig Venter Institute, had constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium and were working on getting it functioning in a living cell.[37][38]

Synthetic transcription factors

Studies have also been performed on the components of the DNA translation mechanism. One desire of scientists creating synthetic biological circuits is to be able to control the translation of synthetic DNA in prokaryotes and eukaryotes. One study tested the adjustability of synthetic transcription factors (sTFs) in areas of transcription output and cooperative ability among multiple transcription factor complexes.[39] Researchers were able to mutate zinc fingers, the DNA specific component of sTFs, to decrease their affinity for DNA, and thus decreasing the amount of translation. They were also able to use the zinc fingers as components of complex forming sTFs, which are the eukaryotic translation mechanisms.[40]

Applications

Synthetic life

Gene functions in the minimal genome of the synthetic organism, Syn 3.[41]

One important topic in synthetic biology is synthetic life, that is, artificial life created in vitro from biomolecules and their component materials. Synthetic life experiments attempt to either probe the origins of life, study some of the properties of life, or more ambitiously to recreate life from non-living (abiotic) components. Synthetic biology attempts to create new biological molecules and even novel living species capable of carrying out a range of important medical and industrial functions, from manufacturing pharmaceuticals to detoxifying polluted land and water.[42] In medicine, it offers prospects of using designer biological parts as a starting point for an entirely new class of therapies and diagnostic tools.[42]

In the area of synthetic biology, a living "artificial cell" has been defined as a completely synthetically-made cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate.[43] Nobody has been able to create such an artificial cell.[43]

The first living organism with 'artificial' DNA was produced by scientists at the Scripps Research Institute as E. coli was engineered to replicate an expanded genetic alphabet.[44]

A completely synthetic genome was produced by Craig Venter, and his team introduced it to genomically emptied bacterial host cells,[45] and allowed the host cells to grow and replicate.[46]

Cell transformation

Currently, entire organisms are not being created from scratch, but instead living cells are being transformed with inserts of new DNA. There are several ways of constructing synthetic DNA components and even entire synthetic genomes, but once the desired genetic code is obtained, it is integrated into a living cell that is expected to manifest the desired new capabilities or phenotypes while growing and thriving.[47] Cell transformation is used to create biological circuits, which can be manipulated to yield desired outputs.[12][13]

Information storage

Scientists can encode vast amounts of digital information onto a single strand of synthetic DNA. In 2012, George M. Church encoded one of his books about synthetic biology in DNA. The 5.3 Mb of data from the book is more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA.[48] A similar project had encoded the complete sonnets of William Shakespeare in DNA.[49]

Synthetic genetic pathways

Traditional metabolic engineering has been bolstered by the introduction of combinations of foreign genes and optimization by directed evolution. Perhaps the best known application of synthetic biology to date is engineering E. coli and yeast for commercial production of a precursor of the antimalarial drug, Artemisinin, by the laboratory of Jay Keasling[50]

Unnatural nucleotides

Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA. By including individual artificial nucleotides in the culture media, were able to exchange the bacteria 24 times; they did not generate mRNA or proteins able to use the artificial nucleotides.[51][52][53]

Unnatural amino acids

Main article: Expanded genetic code

Another common topic of investigation is expansion of the normal repertoire of 20 amino acids. Excluding stop codons, there are 61 codons, but only 20 amino acids are coded generally in all organisms. Certain codons are engineered to code for alternative amino acids including: nonstandard amino acids such as O-methyl tyrosine; or exogenous amino acids such as 4-fluorophenylalanine. Typically, these projects make use of re-coded nonsense suppressor tRNA-Aminoacyl tRNA synthetase pairs from other organisms, though in most cases substantial engineering is still required.[54]

Reduced amino-acid libraries

Instead of expanding the genetic code, other researchers have investigated the structure and function of proteins by reducing the normal set of 20 amino acids. Limited protein sequence libraries are made by generating proteins where certain groups of amino acids may be substituted with a single amino acid.[55] For instance, several non-polar amino acids within a protein can all be replaced with a single non-polar amino acid.[56] One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.[57]

Designed proteins

The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature[58]

While there are methods to engineer natural proteins such as by directed evolution, there are also projects to design novel protein structures that match or improve on the functionality of existing proteins. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide.[59] A similar protein structure was generated to support a variety of oxidoreductase activities.[60] Another group generated a family of G-protein coupled receptors which could be activated by the inert small molecule clozapine-N-oxide but insensitive to the native ligand, acetylcholine.[61]

Biosensors

A biosensor refers to an engineered organism, usually a bacterium, which is capable of reporting some ambient phenomenon such as the presence of heavy metals or toxins. In this capability, a very widely used system is the Lux operon of Aliivibrio fischeri. The Lux operon codes for an enzyme which is the source bacterial bioluminescence, and can be placed after an respondent promoter to express the luminescence genes in response to an specific environmental stimulus. One such sensor created in Oak Ridge National Laboratory, and named "critter on a chip", consisted of a bioluminescent bacterial coating on a photosensitive computer chip to detect certain petroleum pollutants. When the bacteria sense the pollutant, they begin to luminesce.[62]

Materials production

By integrating synthetic biology approaches with materials sciences, it would be possible to envision cells as microscopic molecular foundries to produce materials with properties that can be genetically encoded. Recent advances towards this include re-engineering curli fibers, the amyloid component of extracellular material of biofilms, as a platform for programmable nanomaterial. These nanofibers have been genetically constructed for specific functions, including: adhesion to substrates; nanoparticle templating; and protein immobilization.[63]

Industrial enzymes

Researchers and companies utilizing synthetic biology aim to synthesize enzymes with high activity, to produce products with optimal yields and effectiveness. These synthesized enzymes aim to improve products such as detergents and lactose-free dairy products, as well as make them more cost effective.[64]

The improvements of metabolic engineering by synthetic biology is an example of a biotechnological technique utilized in industry to discover pharmaceuticals and fermentative chemicals. Synthetic biology may investigate modular pathway systems in biochemical production and increase yields of metabolic production. Artificial enzymatic activity and subsequent effects on metabolic reaction rates and yields may develop “efficient new strategies for improving cellular properties . . . for industrially important biochemical production."[65]

Space exploration

Synthetic biology raised NASA’s interest as it could help to produce resources for astronauts from a restricted portfolio of compounds sent from Earth.[66][67][68] On Mars, in particular, synthetic biology could also lead to production processes based on local resources, making it a powerful tool in the development of manned outposts with minimal dependence on Earth.[66]

Bioethics and security

In addition to numerous scientific and technical challenges, synthetic biology raises ethical issues and biosecurity issues. However, with the exception of regulating DNA synthesis companies,[69][70] the issues are not seen as new because they were raised during the earlier recombinant DNA and genetically modified organism (GMO) debates and there were already extensive regulations of genetic engineering and pathogen research in place in the U.S.A., Europe and the rest of the world.[71]

European initiatives

The European Union funded project SYNBIOSAFE[72] has issued several reports on how to manage the risks of synthetic biology. A 2007 paper identified key issues in safety, security, ethics and the science-society interface, which the project defined as public education and ongoing dialogue among scientists, businesses, government, and ethicists).[73][74] The key security issues that SYNBIOSAFE identified involved engaging companies that sell synthetic DNA and the Biohacking community of amateur biologists. Key ethical issues concerned the creation of new life forms.

A subsequent report focused on biosecurity, especially the so-called dual-use challenge. For example, while synthetic biology may lead to more efficient production of medical treatments, for malaria for example(see artemisinin), it may also lead to synthesis or redesign of harmful pathogens (e.g., smallpox).[75] The bio-hacking community remains a source of special concern, as the distributed and diffuse nature of open-source biotechnology makes it difficult to track, regulate, or mitigate potential concerns over biosafety and biosecurity.[76]

COSY, another European initiative, focuses on public perception and communication of synthetic biology.[77][78][79] To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published a 38-minute documentary film in October 2009.[80]

The International Association Synthetic Biology has proposed an initiative for self-regulation.[81] This suggests specific measures that the synthetic biology industry, especially DNA synthesis companies, should implement. In 2007, a group led by scientists from leading DNA-synthesis companies published a "practical plan for developing an effective oversight framework for the DNA-synthesis industry."[69]

USA

In January 2009, the Alfred P. Sloan Foundation funded the Woodrow Wilson Center, the Hastings Center, and the J. Craig Venter Institute to examine the public perception, ethics, and policy implications of synthetic biology.[82]

On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology".[83]

After the publication of the first synthetic genome by Craig Venter's group and the accompanying media coverage about "life" being created, President Obama requested the Presidential Commission for the Study of Bioethical Issues to study synthetic biology.[84] The commission convened a series of meetings, then issued a report in December 2010 titled "New Directions: The Ethics of Synthetic Biology and Emerging Technologies." The commission clarified that the "while Venter’s achievement marked a significant technical advance in demonstrating that a relatively large genome could be accurately synthesized and substituted for another, it did not amount to the “creation of life”.[85] It also noted that synthetic biology is an emerging field, which creates potential risks and rewards. The commission did not recommend any changes to policy or oversight and called for continued funding of the research and new funding for monitoring, study of emerging ethical issues, and public education.[71]

Synthetic biology, being a major tool for biological advances, results in the “potential for developing biological weapons, possible unforeseen negative impacts on human health . . . and any potential environmental impact."[86] These security issues may be avoided by regulating industry uses of biotechnology through policy legislation. Federal guidelines on genetic manipulation are being proposed by “the President’s Bioethics Commission . . . in response to the announced creation of a self-replicating cell from a chemically synthesized genome, put forward 18 recommendations not only for regulating the science . . . for educating the public.”[86]

Opposition to synthetic biology

On March 13, 2012, over 100 environmental and civil society groups, including Friends of the Earth, the International Center for Technology Assessment and the ETC Group issued the manifesto The Principles for the Oversight of Synthetic Biology. This manifesto calls for a worldwide moratorium on the release and commercial use of synthetic organisms until more robust regulations and rigorous biosafety measures are established. The groups specifically call for an outright ban on the use of synthetic biology on the human genome or human microbiome.[87][88] Richard Lewontin wrote that some of the safety tenets for oversight discussed in The Principles for the Oversight of Synthetic Biology are reasonable, but that the main problem with the recommendations in the manifesto is that "the public at large lacks the ability to enforce any meaningful realization of those recommendations."[89]

Ethical concerns

Synthetic biology brings to light a number of questions, including: who will have control and access to the products of synthetic biology, and who will gain from these innovations? Placing patents on living organisms and regulations on bioengineering of human embryos are large concerns in the bioethics field.[90]

See also

References

  1. ↑ IEEE Xplore Abstract - Intellectual Property and the Commons in Synthetic Biology: Strategies to Facilitate an Emerging Tec...
  2. ↑ W97 binnenwerk-8 - Rathenau Constructing Life 2006.pdf
  3. ↑ "Synthetic biology: promises and perils of modern biotechnology". Marsilius Academy Heidelberg – Summer school. Heidelberg University. Retrieved 2014-09-11.
  4. ↑ Nakano, Tadashi (2013). Molecular Communication. Cambridge. ISBN 978-1-107-02308-6.
  5. ↑ "Registry of Standard Biological Parts". Retrieved 2014-09-11.
  6. ↑ "Synthetic-biology firms shift focus". Nature 505 (7485): 598. doi:10.1038/505598a. Retrieved 2014-09-11.
  7. ↑ Osbourn, Anne E.; O'Maille, Paul E.; Rosser, Susan J.; Lindsey, Keith (2012-11-01). "Synthetic biology". New Phytologist 196 (3): 671–677. doi:10.1111/j.1469-8137.2012.04374.x. ISSN 1469-8137.
  8. ↑ Théorie physico-chimique de la vie et générations spontanées, S. Leduc,1910
  9. ↑ Leduc, Stéphane (1912). Poinat, A., ed. La biologie synthétique, étude de biophysique.
  10. ↑ Wacław Szybalski, In Vivo and in Vitro Initiation of Transcription, Page 405. In: A. Kohn and A. Shatkay (Eds.), Control of Gene Expression, pp. 23–4, and Discussion pp. 404–5 (Szybalski's concept of Synthetic Biology), 411–2, 415–7. New York: Plenum Press, 1974
  11. ↑ Szybalski, W; Skalka, A (November 1978). "Nobel prizes and restriction enzymes". Gene 4 (3): 181–2. doi:10.1016/0378-1119(78)90016-1. PMID 744485.
  12. 1 2 Elowitz, Michael B.; Leibler, Stanislas (January 2000). "http://www.nature.com/doifinder/10.1038/35002125". Nature 403 (6767): 335–338. doi:10.1038/35002125. PMID 10659856. External link in |title= (help)
  13. 1 2 Collins, James J.; Gardner, Timothy S.; Cantor, Charles R. (January 2000). "http://www.nature.com/doifinder/10.1038/35002131". Nature 403 (6767): 339–342. doi:10.1038/35002131. PMID 10659857. External link in |title= (help)
  14. ↑ Zeng, Jie (Bangzhe). On the concept of systems bio-engineering. Coomunication on Transgenic Animals, June 1994, CAS, PRC. [cited 1994-06-05];6.
  15. ↑ Chopra, Paras; Akhil Kamma. "Engineering life through Synthetic Biology". In Silico Biology 6. Retrieved 2008-06-09.
  16. ↑ Channon, Kevin; Bromley, Elizabeth HC; Woolfson, Derek N (August 2008). "Synthetic Biology through Biomolecular Design and Engineering". Current Opinion in Structural Biology 18 (4): 491–8. doi:10.1016/j.sbi.2008.06.006. PMID 18644449.
  17. ↑ Stone, M (2006). "Life Redesigned to Suit the Engineering Crowd" (PDF). Microbe 1 (12): 566–570.
  18. ↑ Group, Bio FAB; Baker D; Church G; Collins J; Endy D; Jacobson J; Keasling J; Modrich P; Smolke C; Weiss R (June 2006). "Engineering life: building a fab for biology". Scientific American 294 (6): 44–51. doi:10.1038/scientificamerican0606-44. PMID 16711359.
  19. 1 2 "Synthetic Biology – A Primer". World Scientific. 2012. ISBN 978-1-84816-863-3.
  20. ↑ "Tom Knight (2003). Idempotent Vector Design for Standard Assembly of Biobricks". Retrieved 2014-09-26.
  21. ↑ Pollack, Andrew (2007-09-12). "How Do You Like Your Genes? Biofabs Take Orders". The New York Times. ISSN 0362-4331. Retrieved 2007-12-28.
  22. ↑ Forster, AC; Church GM (2006-08-22). "Towards synthesis of a minimal cell". Mol Syst Biol. 2 (1): 45. doi:10.1038/msb4100090. PMC 1681520. PMID 16924266.
  23. 1 2 Basulto, Dominic (November 4, 2015). "Everything you need to know about why CRISPR is such a hot technology". Washington Post. Retrieved 5 December 2015.
  24. ↑ Kahn, Jennifer (November 9, 2105). "The Crispr Quandary". New York Times. Retrieved 5 December 2015. Check date values in: |date= (help)
  25. ↑ Ledford, Heidi (June 3, 2015). "CRISPR, the disruptor". Nature. Nature News. Retrieved 5 December 2015.
  26. ↑ Higginbotham, Stacey (4 December 2015). "Top VC Says Gene Editing Is Riskier Than Artificial Intelligence". Fortune. Retrieved 5 December 2015.
  27. ↑ Rollie; et al. (2012). "Designing biological systems: Systems Engineering meets Synthetic Biology". Chemical Engineering Science 69 (1): 1–29. doi:10.1016/j.ces.2011.10.068.
  28. ↑ Woolfson DN (2012). "New currency for old rope: from coiled-coil assemblies to α-helical barrels". Curr Op Struct Biol 22: 432. doi:10.1016/j.sbi.2012.03.002. PMID 22445228.
  29. ↑ Dueber JE (2009). "Synthetic protein scaffolds provide modular control over metabolic flux". Nat Biotech 27: 753. doi:10.1038/nbt.1557. PMID 19648908.
  30. ↑ Reddington SC (2015). "Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher". Curr Op Chem Biol 29: 94. doi:10.1016/j.cbpa.2015.10.002. PMID 26517567.
  31. ↑ Bayle JH (2006). "Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity". Chem Biol 13: 99. doi:10.1016/j.chembiol.2005.10.017. PMID 16426976.
  32. ↑ Kaznessis YN (2007). "Models for synthetic biology". BMC Systems Biology 1 (1): 47. doi:10.1186/1752-0509-1-47. PMC 2194732. PMID 17986347.
  33. ↑ Kosuri, S. & Church, G.M. (2014). "Large-scale de novo DNA synthesis: technologies and applications". Nature Methods 11 (5): 499–507. doi:10.1038/nmeth.2918.
  34. ↑ Blight KJ; Kolykhalov AA; Rice CM (2000-12-08). "Efficient initiation of HCV RNA replication in cell culture". Science 290 (5498): 1972–4. doi:10.1126/science.290.5498.1972. PMID 11110665.
  35. ↑ Couzin J (2002). "Virology. Active poliovirus baked from scratch". Science 297 (5579): 174–5. doi:10.1126/science.297.5579.174b. PMID 12114601.
  36. ↑ Smith, Hamilton O.; Clyde A. Hutchison; Cynthia Pfannkoch; J. Craig Venter (2003-12-23). "Generating a synthetic genome by whole genome assembly: {phi}X174 bacteriophage from synthetic oligonucleotides". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15440–5. doi:10.1073/pnas.2237126100. PMC 307586. PMID 14657399.
  37. ↑ Wade, Nicholas (2007-06-29). "Scientists Transplant Genome of Bacteria". The New York Times. ISSN 0362-4331. Retrieved 2007-12-28.
  38. ↑ Gibson, DG; Benders GA; Andrews-Pfannkoch C; Denisova EA; Baden-Tillson H; Zaveri J; Stockwell TB; Brownley A; Thomas DW; Algire MA; Merryman C; Young L; Noskov VN; Glass JI; Venter JC; Hutchison CA 3rd; Smith HO (2008-01-24). "Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome". Science 319 (5867): 1215–20. doi:10.1126/science.1151721. PMID 18218864.
  39. ↑ Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J. (2012-03-08). "A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions". Cell 150 (3): 647–658. doi:10.1016/j.cell.2012.05.045. ISSN 0092-8674. PMC 3653585. PMID 22863014.
  40. ↑ Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J. (2012-03-08). "A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions". Cell 150 (3): 647–658 volume = 150. doi:10.1016/j.cell.2012.05.045. ISSN 0092-8674. PMC 3653585. PMID 22863014.
  41. ↑ Hutchison, Clyde A.; Chuang, Ray-Yuan; Noskov, Vladimir N.; Assad-Garcia, Nacyra; Deerinck, Thomas J.; Ellisman, Mark H.; Gill, John; Kannan, Krishna; Karas, Bogumil J. (2016-03-25). "Design and synthesis of a minimal bacterial genome". Science 351 (6280): aad6253. doi:10.1126/science.aad6253. ISSN 0036-8075. PMID 27013737.
  42. 1 2 Connor, Steve (1 December 2014). "Major synthetic life breakthrough as scientists make the first artificial enzymes". The Independent (London). Retrieved 2015-08-06.
  43. 1 2 Deamer, D (July 2005). "A giant step towards artificial life?". Trends in Biotechnology 23 (7): 336–8. doi:10.1016/j.tibtech.2005.05.008. PMID 15935500.
  44. ↑ Malyshev, Denis A.; Dhami, Kirandeep; Lavergne, Thomas; Chen, Tingjian; Dai, Nan; Foster, Jeremy M.; Corrêa, Ivan R.; Romesberg, Floyd E. "A semi-synthetic organism with an expanded genetic alphabet". Nature 509 (7500): 385–388. doi:10.1038/nature13314. PMC 4058825. PMID 24805238.
  45. ↑ Gibson, D. G.; Glass, J. I.; Lartigue, C.; Noskov, V. N.; Chuang, R.-Y.; Algire, M. A.; Benders, G. A.; Montague, M. G.; Ma, L.; Moodie, M. M.; Merryman, C.; Vashee, S.; Krishnakumar, R.; Assad-Garcia, N.; Andrews-Pfannkoch, C.; Denisova, E. A.; Young, L.; Qi, Z.-Q.; Segall-Shapiro, T. H.; Calvey, C. H.; Parmar, P. P.; Hutchison, C. A.; Smith, H. O.; Venter, J. C. (20 May 2010). "Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome". Science 329 (5987): 52–56. doi:10.1126/science.1190719. PMID 20488990.
  46. ↑ "Scientists Reach Milestone On Way To Artificial Life". 2010-05-20. Retrieved 2010-06-09.
  47. ↑ Connor, Steve (28 March 2014). "Eureka! Scientists unveil giant leap towards synthetic life". The Independent. Retrieved 2015-08-06.
  48. ↑ Church, G.M.; et al. (2012). "Next-Generation Digital Information Storage in DNA". Science 337 (6102): 1628. doi:10.1126/science.1226355. PMID 22903519.
  49. ↑ "Huge amounts of data can be stored in DNA". Sky News. 23 January 2013. Retrieved 24 January 2013.
  50. ↑ Westfall, P. J., Pitera, D. J., Lenihan, J. R., Eng, D., Woolard, F. X., Regentin, R., ... & Fickes, S. (2012). Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proceedings of the National Academy of Sciences, 109(3), E111-E118.
  51. ↑ Pollack, Andrew (May 7, 2014). "Researchers Report Breakthrough in Creating Artificial Genetic Code". New York Times. Retrieved May 7, 2014.
  52. ↑ Callaway, Ewen (May 7, 2014). "First life with 'alien' DNA". Nature. doi:10.1038/nature.2014.15179. Retrieved May 7, 2014.
  53. ↑ Malyshev, Denis A.; Dhami, Kirandeep; Lavergne, Thomas; Chen, Tingjian; Dai, Nan; Foster, Jeremy M.; Corrêa, Ivan R.; Romesberg, Floyd E. (May 7, 2014). "A semi-synthetic organism with an expanded genetic alphabet". Nature 509 (7500): 385–388. doi:10.1038/nature13314. PMC 4058825. PMID 24805238. Retrieved May 7, 2014.
  54. ↑ Wang, Qian; Parrish, Angela R; Wang, Lei (2009). "Expanding the genetic code for biological studies". Chemistry and Biology 16 (3): 323–36. doi:10.1016/j.chembiol.2009.03.001. PMC 2696486. PMID 19318213.
  55. ↑ Davidson, AR; Lumb, KJ; Sauer, RT (1995). "Cooperatively folded proteins in random sequence libraries". Nature Structural Biology 2 (10): 856–864. doi:10.1038/nsb1095-856.
  56. ↑ Kamtekar, S.; Schiffer, J.; Xiong, H.; Babik, J.; Hecht, M. (1993). "Protein design by binary patterning of polar and nonpolar amino acids". Science 262 (5140): 1680–1685. doi:10.1126/science.8259512. PMID 8259512.
  57. ↑ Walter, K.U.; Vamvaca, K.; Hilvert, D. (2005). "An active enzyme constructed from a 9-amino acid alphabet". The Journal of Biological Chemistry 280 (45): 37742–6. doi:10.1074/jbc.M507210200. PMID 16144843.
  58. ↑ Kuhlman, B; Dantas, G; Ireton, GC; Varani, G; Stoddard, BL; Baker, D (November 21, 2003). "Design of a novel globular protein fold with atomic-level accuracy.". Science 302 (5649): 1364–8. Bibcode:2003Sci...302.1364K. doi:10.1126/science.1089427. PMID 14631033.
  59. ↑ Koder, RL; et al. (2009). "Design and engineering of an O(2) transport protein". Nature 458 (7236): 305–9. doi:10.1038/nature07841. PMC 3539743. PMID 19295603.
  60. ↑ Farid, TA; Kodali, G.; Solomon, LA; et al. (2013). "Elementary tetrahelical protein design for diverse oxidoreductase functions". Nature Chemical Biology 9 (12): 826–33. doi:10.1038/nchembio.1362. PMID 24121554.
  61. ↑ Armbruster BN; Li X; Pausch MH; Herlitze S; Roth BL (2007). "Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand". PNAS USA 104 (12): 5163–8. doi:10.1073/pnas.0700293104. PMC 1829280. PMID 17360345.
  62. ↑ Gibbs, W. Wayt (1997). "Critters on a Chip". Scientific American. Retrieved 2 Mar 2009.
  63. ↑ Nguyen, Peter; Botyanszki, Zsofia; Tay, Pei-Kun; Joshi, Neel (Sep 17, 2014). "Programmable biofilm-based materials from engineered curli nanofibres". Nature Communications 5: 4945. doi:10.1038/ncomms5945. PMID 25229329.
  64. ↑ "Synthetic Biology Applications". www.thermofisher.com. Retrieved 2015-11-12.
  65. ↑ Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long (2014-12-31). "Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects". Applied Microbiology and Biotechnology 99 (3): 1109–1118. doi:10.1007/s00253-014-6298-y. ISSN 0175-7598.
  66. 1 2 Verseux, C.; Paulino-Lima, I.; Baque, M.; Billi, D.; Rothschild, L. (2016). "Synthetic Biology for Space Exploration: Promises and Societal Implications". Ambivalences of Creating Life. Societal and Philosophical Dimensions of Synthetic Biology, Publisher: Springer-Verlag: 73–100. doi:10.1007/978-3-319-21088-9_4.
  67. ↑ Menezes, A; Cumbers, J; Hogan, J; Arkin, A (2014). "Towards synthetic biological approaches to resource utilization on space missions". Journal of the Royal Society, Interface 12.
  68. ↑ Montague, M; et al. (2012). "The Role of Synthetic Biology for In Situ Resource Utilization (ISRU).". Astrobiology 12 (12): 1135–1142. doi:10.1089/ast.2012.0829.
  69. 1 2 Bügl, H.; et al. (2007). "DNA synthesis and biological security". Nature Biotechnology 25 (6): 627–629. doi:10.1038/nbt0607-627.
  70. ↑ "Ethical Issues in Synthetic Biology: An Overview of the Debates" (PDF).
  71. 1 2 Presidential Commission for the study of Bioethical Issues, December 2010 NEW DIRECTIONS The Ethics of Synthetic Biology and Emerging Technologies Retrieved 2012-04-14.
  72. ↑ SYNBIOSAFE official site
  73. ↑ Schmidt M; Ganguli-Mitra A; Torgersen H; Kelle A; Deplazes A; Biller-Andorno N (2009). "A priority paper for the societal and ethical aspects of synthetic biology" (PDF). Systems and Synthetic Biology 3 (1–4): 3–7. doi:10.1007/s11693-009-9034-7. PMC 2759426. PMID 19816794.
  74. ↑ Schmidt M. Kelle A. Ganguli A, de Vriend H. (Eds.) 2009. "Synthetic Biology. The Technoscience and its Societal Consequences". Springer Academic Publishing.
  75. ↑ Kelle A (2009). "Ensuring the security of synthetic biology—towards a 5P governance strategy" (PDF). Systems and Synthetic Biology 3 (1–4): 85–90. doi:10.1007/s11693-009-9041-8. PMC 2759433. PMID 19816803.
  76. ↑ Schmidt M (2008). "Diffusion of synthetic biology: a challenge to biosafety" (PDF). Systems and Synthetic Biology 2 (1–2): 1–6. doi:10.1007/s11693-008-9018-z. PMC 2671588. PMID 19003431.
  77. ↑ COSY: Communicating Synthetic Biology
  78. ↑ Kronberger, N; Holtz, P; Kerbe, W; Strasser, E; Wagner, W (2009). "Communicating Synthetic Biology: from the lab via the media to the broader public" (PDF). Systems and Synthetic Biology 3 (1–4): 19–26. doi:10.1007/s11693-009-9031-x. PMC 2759424. PMID 19816796.
  79. ↑ Cserer A; Seiringer A (2009). "Pictures of Synthetic Biology: A reflective discussion of the representation of Synthetic Biology (SB) in the German-language media and by SB experts" (PDF). Systems and Synthetic Biology 3 (1–4): 27–35. doi:10.1007/s11693-009-9038-3. PMC 2759430. PMID 19816797.
  80. ↑ COSY/SYNBIOSAFE Documentary
  81. ↑ Report of IASB "Technical solutions for biosecurity in synthetic biology", Munich, 2008
  82. ↑ Parens E., Johnston J., Moses J. Ethical Issues in Synthetic Biology. 2009.
  83. ↑ NAS Symposium official site
  84. ↑ Presidential Commission for the study of Bioethical Issues, December 2010 FAQ
  85. ↑ Synthetic Biology F.A.Q.'s | Presidential Commission for the Study of Bioethical Issues
  86. 1 2 Erickson, Brent; Singh, Rina; Winters, Paul (2011-09-02). "Synthetic Biology: Regulating Industry Uses of New Biotechnologies". Science 333 (6047): 1254–1256. doi:10.1126/science.1211066. ISSN 0036-8075. PMID 21885775.
  87. ↑ Katherine Xue for Harvard Magazine. September–October 2014 Synthetic Biology’s New Menagerie
  88. ↑ Yojana Sharma for Scidev.net March 15, 2012. NGOs call for international regulation of synthetic biology
  89. ↑ The New Synthetic Biology: Who Gains? (2014-05-08), Richard C. Lewontin, New York Review of Books
  90. ↑ Savulescu, Julian; Pugh, Jonathan; Douglas, Thomas; Gyngell, Christopher (2015-06-26). "The moral imperative to continue gene editing research on human embryos". Protein & Cell 6 (7): 476–479. doi:10.1007/s13238-015-0184-y. ISSN 1674-800X. PMC 4491050. PMID 26113289.

External links

This article is issued from Wikipedia - version of the Tuesday, April 26, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.