Graphical Abstracts Xenobiology, New-To-Nature Synthetic Cells And
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This Article Appeared in a Journal Published by Elsevier. the Attached
This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright Author's personal copy Available online at www.sciencedirect.com Recent advances in genetic code engineering in Escherichia coli Michael Georg Hoesl and Nediljko Budisa The expansion of the genetic code is gradually becoming a modifications (PTMs). These reactions are selectively core discipline in Synthetic Biology. It offers the best possible and timely coordinated chemistries performed by dedi- platform for the transfer of numerous chemical reactions and cated enzymes and enzymatic complexes, usually in processes from the chemical synthetic laboratory into the specialized cell compartments. biochemistry of living cells. The incorporation of biologically occurring or chemically synthesized non-canonical amino Certainly, one of the main goals of Synthetic Biology is acids into recombinant proteins and even proteomes via to generate new and emergent biological functions in reprogrammed protein translation is in the heart of these streamlined cells which are equipped with ‘tailor-made efforts. Orthogonal pairs consisting of aminoacyl-tRNA biochemical production lines’. However, it is extremely synthetase and its cognate tRNA proved to be a general difficult to mimic nature’s complex machineries such as tool for the assignment of certain codons of the genetic code the PTM-apparatus. -
Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation
G C A T T A C G G C A T genes Review Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation Christian Diwo 1 and Nediljko Budisa 1,2,* 1 Institut für Chemie, Technische Universität Berlin Müller-Breslau-Straße 10, 10623 Berlin, Germany; [email protected] 2 Department of Chemistry, University of Manitoba, 144 Dysart Rd, 360 Parker Building, Winnipeg, MB R3T 2N2, Canada * Correspondence: [email protected] or [email protected]; Tel.: +49-30-314-28821 or +1-204-474-9178 Received: 27 November 2018; Accepted: 21 December 2018; Published: 28 December 2018 Abstract: The universal genetic code, which is the foundation of cellular organization for almost all organisms, has fostered the exchange of genetic information from very different paths of evolution. The result of this communication network of potentially beneficial traits can be observed as modern biodiversity. Today, the genetic modification techniques of synthetic biology allow for the design of specialized organisms and their employment as tools, creating an artificial biodiversity based on the same universal genetic code. As there is no natural barrier towards the proliferation of genetic information which confers an advantage for a certain species, the naturally evolved genetic pool could be irreversibly altered if modified genetic information is exchanged. We argue that an alien genetic code which is incompatible with nature is likely to assure the inhibition of all mechanisms of genetic information transfer in an open environment. The two conceivable routes to synthetic life are either de novo cellular design or the successive alienation of a complex biological organism through laboratory evolution. -
Orthogonal Dual-Modification of Proteins for the Engineering of Multivalent Protein Scaffolds
Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds Michaela Mühlberg‡1,2, Michael G. Hoesl‡3, Christian Kuehne4, Jens Dernedde4, Nediljko Budisa*3 and Christian P. R. Hackenberger*1,5,§ Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2015, 11, 784–791. 1Forschungsinstitut für Molekulare Pharmakologie (FMP), doi:10.3762/bjoc.11.88 Robert-Roessle-Str. 10, 13125 Berlin, Germany, 2Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Received: 11 February 2015 Germany, 3Technische Universität Berlin, AK Biokatalyse, Institut für Accepted: 05 May 2015 Chemie, Müller-Breslau-Str. 10, 10623 Berlin, Germany, 4Charité - Published: 13 May 2015 Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Augustenburger Platz 1, This article is part of the Thematic Series "Multivalency as a chemical 13353 Berlin, Germany and 5Humboldt Universität zu Berlin, Institut organization and action principle". für Organische und Bioorganische Chemie, Institut für Chemie, Brook-Taylor-Str. 2, 12489 Berlin, Germany Guest Editor: R. Haag Email: © 2015 Mühlberg et al; licensee Beilstein-Institut. Nediljko Budisa* - [email protected]; License and terms: see end of document. Christian P. R. Hackenberger* - [email protected] * Corresponding author ‡ Equal contributors § Fax: +49 (0)30 94793-188 Keywords: chemoselectivity; dual protein modification; lectin; multivalency Abstract To add new tools to the repertoire of protein-based multivalent scaffold design, we have developed a novel dual-labeling strategy for proteins that combines residue-specific incorporation of unnatural amino acids with chemical oxidative aldehyde formation at the N-terminus of a protein. Our approach relies on the selective introduction of two different functional moieties in a protein by mutually orthogonal copper-catalyzed azide–alkyne cycloaddition (CuAAC) and oxime ligation. -
Flourishing and Discordance: on Two Modes of Human Science Engagement with Synthetic Biology
Flourishing and Discordance: On Two Modes of Human Science Engagement with Synthetic Biology by Anthony Stavrianakis A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Anthropology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Paul Rabinow, Chair Professor Xin Liu Professor Charis Thompson Fall 2012 Abstract Flourishing and Discordance: On Two Modes of Human Science Engagement with Synthetic Biology by Anthony Stavrianakis Doctor of Philosophy in Anthropology University of California, Berkeley Professor Paul Rabinow, Chair This dissertation takes up the theme of collaboration between the human sciences and natural sciences and asks how technical, veridictional and ethical vectors in such co-labor can be inquired into today. I specify the problem of collaboration, between forms of knowledge, as a contemporary one. This contemporary problem links the recent past of the institutional relations between the human and natural sciences to a present experience of anthropological engagement with a novel field of bioengineering practice, called synthetic biology. I compare two modes of engagement, in which I participated during 2006–2011. One project, called Human Practices, based within the Synthetic Biology Engineering Research Center (SynBERC), instantiated an anthropological mode of inquiry, explicitly oriented to naming ethical problems for collaboration. This project, conducted in collaboration with Paul Rabinow and Gaymon Bennett, took as a challenge the invention of an appropriate practice to indeterminate ethical problems. Flourishing, a translation of the ancient Greek term eudaemonia, was a central term in orienting the Human Practices project. This term was used to posit ethical questions outside of the instrumental rationality of the sciences, and on which the Human Practices project would seek to work. -
21St Century Borders/Synthetic Biology: Focus on Responsibility and Governance
Social science Engineering Framework Institute on Science for Global Policy (ISGP) Risk-benefit Media Public Synthetic Biology Genetic Governance Regulation Voluntary Anticipatory Databases Xenobiology 21st Century Borders/Synthetic Biology: Focus on Responsibility and Governance Conference convened by the ISGP Dec. 4–7, 2012 at the Hilton El Conquistador, Tucson, Arizona Risk Technology Oversight Plants Uncertainty Product Less-affluent countries DIYBIO Biotechnology Emerging Dynamic Environmental Government Biosafety Self-regulation Nefarious Genetically modified Protein Standards Dual use Distribution Applications Food Microbial Authority Assessment Agricultural Institute on Science for Global Policy (ISGP) 21st Century Borders/Synthetic Biology: Focus on Responsibility and Governance Conference convened by the ISGP in partnership with the University of Arizona at the Hilton El Conquistador Hotel Tucson, Arizona, U.S. Dec. 4–7, 2012 An ongoing series of dialogues and critical debates examining the role of science and technology in advancing effective domestic and international policy decisions Institute on Science for Global Policy (ISGP) Tucson, AZ Office 845 N. Park Ave., 5th Floor PO Box 210158-B Tucson, AZ 85721 Washington, DC Office 818 Connecticut Ave. NW Suite 800 Washington, DC 20006 www.scienceforglobalpolicy.org © Copyright Institute on Science for Global Policy, 2013. All rights reserved. ISBN: 978-0-9803882-4-0 ii Table of contents Executive summary • Introduction: Institute on Science for Global Policy (ISGP) .............. 1 Dr. George H. Atkinson, Founder and Executive Director, ISGP, and Professor Emeritus, University of Arizona • Conference conclusions: Areas of consensus and Actionable next steps ...................................... 7 Conference program ........................................................................................... 11 Policy position papers and debate summaries • Synthetic Biology — Do We Need New Regulatory Systems? Prof. -
1 Engineering Lipases with an Expanded Genetic Code Alessandro De Simone, Michael Georg Hoesl, and Nediljko Budisa
3 1 Engineering Lipases with an Expanded Genetic Code Alessandro De Simone, Michael Georg Hoesl, and Nediljko Budisa 1.1 Introduction Lipases (EC 3.1.1.3) are a class of ubiquitous enzymes that catalyze both the hydrolysis and synthesis of acylglycerols with long acyl chains (carbon atoms >10) [1]. Currently, they constitute one of the most important groups of biocatalysts applied in many fields, including foods, detergents, flavors, fine chemicals, cosmetics, biodiesel, and pharmaceuticals owing to their high specificity, regios- electivity, and enantioselectivity [2]. Lipases can be found in a broad range of organisms, including plants and animals, however, it is chiefly the microbial lipases that find immense application. This is because of their high yields and ease of genetic manipulation, as well as wide substrate specificity [3]. Although lipases’ properties (molecular weight, pH and temperature optima, stability, substrate specificity) are source dependent, they all share a common structure consisting of a compact minimal α/β hydrolase fold. The hydrolase fold is composed of a central β-sheet consisting of up to eight different β strands connected by up to six α helices [1]. The active site of the α/β hydrolase fold enzymes contains a nucleophilic residue (serine), a catalytic acid residue (aspartate/glutamate), and a histidine residue, always in this order in the amino acid sequence. These residues act cooperatively in the catalytic mechanism of ester hydrolysis [4]. The lipolytic reaction takes place at the interface between an insoluble substrate phase and the aqueous phase in which the enzyme is dissolved. Lipases are activated by the presence of this emulsion interface, a phenomenon called interfacial activation, which differentiates them from similar esterases. -
Astrobiology Life in the Universe
Astrobiology Astrobiology is the study of the origin, evolution, distribution, and future of life in the universe. In simplest terms, it is the study of life in the universe–both on Earth and off it. It combines the search for habitable environments in the Solar System and beyond with research into the evolution and adaptability of life here on Earth. By knitting together research in astrophysics, earth science, and heliophysics as well as planetary science, astrobiology seeks to answer fundamental scientific questions about life: how it begins and evolves; what biological, planetary, and cosmic conditions must exist in order for it to take hold; and whether there is/was/can be life elsewhere in the galaxy. Dr. Alka Misra Assistant Professor Department of Mathematics & Astronomy University of Lucknow What is Astrobiology! Astrobiology is the study of life in the Universe – where it is, how it came to be there, what it is like, and where it might be going. As the only life we know about for sure is on Earth, a lot of astrobiology is about trying to predict where we might find life elsewhere. Astrobiology is the study of the origin, evolution, distribution, and future of life in the universe. This interdisciplinary field encompasses the search for habitable environments in our Solar System and habitable planets outside our Solar System, the search for evidence of prebiotic chemistry, laboratory and field research into the origins and early evolution of life on Earth, and studies of the potential for life to adapt to challenges on Earth and in outer space. -
Synthetic Biology in Agriculture and Challenges for Risk Governance
Synthetic biology in agriculture and challenges for risk governance STOA Workshop on Ethical and social challenges of agricultural technologies European Parliament, 25th January 2017 Helge Torgersen Synthetic biology, agriculture and risk govenance 1. What is synthetic biology? 2. Novel risk aspects – what relevance for agriculture? 3. Gene editing – the pertinent example: Definition: what is a GMO? Assessment: how to compare an edited organism? Containment: gene drive Public perception: edited animals 4. Risk governance 5. Strategies 1) What is Synthetic Biology? • Introducing into biotechnology concepts from computer science and systems engineering (Endy 2005) The design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural systems (UK Royal Society 2014) • ‘Extreme genetic engineering’ (ETC Group 2007) The application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms (SCHER/SCENIHR/SCCS 2015) Synthetic biology is a compilation of novel bio-engineering approaches with no clear distinction from genetic engineering, from which it evolves (1) Relevant fields (SCHER/SCENHIR/SCCS 2015) a. Genetic parts: pieces of DNA governing particular functions in an organism, to be deliberately combined b. Protocells: artificial cell-like devices that perform some functions of a living cell c. Minimal cells deprived of all non-essential genes used as a “chassis” for genetic parts d. Xenobiology: -
Epistemological Roots and Blind Spots of Synthetic Biology
BIO Web of Conferences 4, 00016 (2015) DOI: 10.1051/bioconf/20150400016 C Owned by the authors, published by EDP Sciences, 2015 Can life be engineered? Epistemological roots and blind spots of Synthetic Biology Thomas Heams1,2,a 1 INRA, UMR 1313, Génétique Animale et Biologie Intégrative, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France 2 AgroParisTech, Département Sciences de la Vie et Santé, 16 rue Claude Bernard, 75231 Paris Cedex 05, France Abstract. Synthetic Biology is the latest attempt in experimental biology to reach the long lasting goal of mastering processes of life by engineering them. This emergent discipline results from the novel convergence of biology and concept and tools from other fields such as computing and engineering sciences. It relies on rational design of bioparts, modules, or organisms, as opposed to the tinkering methods provided so far by the even most sophisticated biotechnologies. Such an approach could have major consequences, for both applied and fundamental research. But this appealing narrative may obscure important epistemological issues, some of them being rooted in old misconceptions or shortcomings in biology. By focusing mainly on the mechanistic dimension of living beings, Synthetic Biology partially recycle ancient debates and could miss the opportunity to provide an integrative account of what makes life actually specific in the natural world. A first insight into a critical reassessment of some of the goals, the lexicon, and the theoretical foundations of Synthetic Biology is proposed, as other natural dimensions of the biological world are highlighted. Taken as a whole, these considerations challenge several core concepts of the discipline, but may help to redefine some of its strategies and overcome some major hurdles. -
Expanding the Toolkit of Protein Engineering: Towards Multiple Simultaneous in Vivo Incorporation of Noncanonical Amino Acids
TECHNISCHE UNIVERSITÄT MÜNCHEN Max-Planck-Institut für Biochemie Expanding the Toolkit of Protein Engineering: Towards Multiple Simultaneous In Vivo Incorporation of Noncanonical Amino Acids Michael G. Hösl Vollständiger Abdruck der von der Fakultät für Chemie der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. Michael Groll Prüfer der Dissertation: 1. Univ.-Prof. Dr. Nediljko Budisa, Technische Universität Berlin 2. Univ.-Prof. Dr. Thomas Kiefhaber 3. Univ.-Prof. Dr. Johannes Buchner Die Dissertation wurde am 01.02.11 bei der Technischen Universität München eingereicht und durch die Fakultät für Chemie am 03.03.11 angenommen. To Teresa Ariadna García-Grajalva Lucas who influenced the idea of TAG → AGG switch just by the existence of her name Sleeping is giving in, no matter what the time is. Sleeping is giving in, so lift those heavy eyelids. People say that you'll die faster than without water. But we know it's just a lie, scare your son, scare your daughter. People say that your dreams are the only things that save ya. Come on baby in our dreams, we can live on misbehavior. The Arcade Fire Parts of this work were published as listed below: Hoesl, MG, Budisa, N. Expanding and engineering the genetic code in a single expression experiment. ChemBioChem 2011, 12, 552-555. Further publications: Hoesl, MG*, Staudt, H*, Dreuw, A, Budisa, N, Grininger, M, Oesterhelt, D, Wachtveitl, J. Manipulating the eletron transfer in Dodecin by isostructual noncanonical Trp analogs. 2011, [in preparation]. *authors contributed equally to this work Nehring, S*, Hoesl, MG*, Acevedo-Rocha, CG*, Royter, M, Wolschner, C, Wiltschi, B, Budisa, N, Antranikian, G. -
Tesis Doctoral Presentada Por: Da
UNIVERSIDAD CATÓLICA DE VALENCIA SAN VICENTE MÁRTIR ETHICAL ISSUES OF SYNTHETIC BIOLOGY: A PERSONALIST PERSPECTIVE Tesis doctoral Presentada por: Da. LUCÍA GÓMEZ TATAY Dirigida por: DR. D. JOSÉ MIGUEL HERNÁNDEZ ANDREU 2019 1 2 4 Agradecimientos Gracias A José Miguel, que es parte de esta tesis. A Samuel, que es parte de mí. A Justo, Nuria, Manuel, Ester y Cristina, que han sido parte de mi día a día en la realización de este trabajo. A Dios, por todo. 5 6 ABSTRACT Synthetic Biology is a scientific area that combines biology and engineering to build new biological systems that could provide solutions to a wide range of social needs. Multiple and promising applications are expected from this discipline. However, Synthetic Biology also raises several ethical concerns that need to be addressed, not only to protect those values that may be threatened by the different applications of this discipline, but also because failure to fully confront them could be, together with social rejection, an obstacle to the realization of these applications. This work has been carried out under the hypothesis that a detailed study of the current state of Synthetic Biology from a personalist perspective will highlight the main bioethical issues that could be a threat for a genuine development, respectful of human life and dignity, and provide solutions for it to become a reality. The main objective of this thesis is to assess the bioethical issues raised by Synthetic Biology from a specific bioethical approach, personalism, specifically ontological personalism, a philosophy that shows the objective value of the person on the basis of its ontological structure. -
Xenobiology: a New Form of Life As the Ultimate Biosafety Tool Markus Schmidt* Organisation for International Dialogue and Conflict Management, Kaiserstr
Review article DOI 10.1002/bies.200900147 Xenobiology: A new form of life as the ultimate biosafety tool Markus Schmidt* Organisation for International Dialogue and Conflict Management, Kaiserstr. 50/6, 1070 Vienna, Austria Synthetic biologists try to engineer useful biological search for alternatives. They belong to apparently very systems that do not exist in nature. One of their goals different science fields and their quest for biochemical is to design an orthogonal chromosome different from diversity is driven by different motivations.(1–3) The science DNA and RNA, termed XNA for xeno nucleic acids. XNA exhibits a variety of structural chemical changes relative fields in question include four areas: origin of life, exobiology, to its natural counterparts. These changes make this systems chemistry, and synthetic biology (SB). The ancient novel information-storing biopolymer ‘‘invisible’’ to nat- Greeks, including Aristotle, believed in Generatio spontanea, ural biological systems. The lack of cognition to the the idea that life could suddenly come into being from non- natural world, however, is seen as an opportunity to living matter on an every day basis. Spontaneous generation implement a genetic firewall that impedes exchange of genetic information with the natural world, which means of life, however, was finally discarded by the scientific it could be the ultimate biosafety tool. Here I discuss, why experiments of Pasteur, whose empirical results showed that it is necessary to go ahead designing xenobiological modern organisms do not spontaneously arise in nature from systems like XNA and its XNA binding proteins; what non-living matter. On the sterile earth 4 billion years ago, the biosafety specifications should look like for this however, abiogenesis must have happened at least once, genetic enclave; which steps should be carried out to boot up the first XNA life form; and what it means for the eventually leading to the last universal common ancestor society at large.