{"id":9,"date":"2024-12-01T00:37:28","date_gmt":"2024-11-30T23:37:28","guid":{"rendered":"https:\/\/xenome.genoscope.cns.fr\/?page_id=9"},"modified":"2024-12-19T16:31:14","modified_gmt":"2024-12-19T15:31:14","slug":"research","status":"publish","type":"page","link":"https:\/\/xenome.genoscope.cns.fr\/fr\/research\/","title":{"rendered":"Recherches"},"content":{"rendered":"
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Le code g\u00e9n\u00e9tique naturel de toutes les formes de vie sur notre plan\u00e8te n'est reconnu que sous la forme de polym\u00e8res d'ADN et d'ARN. \nUne approche solide pour g\u00e9n\u00e9rer des OGMs s\u00fbrs consiste \u00e0 d\u00e9velopper un acide nucl\u00e9ique orthogonal, chimiquement distinct de l'ADN et de l'ARN, mais qui peut h\u00e9berger des informations structurelles et\/ou s\u00e9quentielles essentielles \u00e0 la viabilit\u00e9 et au ph\u00e9notype des cellules. Un tel acide nucl\u00e9ique x\u00e9nobiotique (XNA) sera g\u00e9n\u00e9tiquement inerte et ne pourra \u00eatre pris en charge que par des enzymes artificielles et synth\u00e9tis\u00e9 \u00e0 partir de ses pr\u00e9curseurs x\u00e9nonucl\u00e9otides (XN). \nCes OGM \u00ab s\u00fbrs \u00bb ouvrent de nouveaux horizons pour les applications biotechnologiques et industrielles ; en tant que formes de vie non naturelles, ils contribuent \u00e9galement \u00e0 une meilleure compr\u00e9hension des organismes naturels.
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XNAs dans les syst\u00e8mes artificiels<\/h2>\n\n\n\n

Notre objectif est de d\u00e9velopper un syst\u00e8me d'information artificiel bas\u00e9 sur un nouveau type d'acides nucl\u00e9iques qui pourrait fonctionner in vivo ind\u00e9pendamment du syst\u00e8me d'information naturel. Pour atteindre cet objectif, quatre \u00e9tapes doivent \u00eatre \u00e9labor\u00e9es : la s\u00e9lection de la chimie du squelette, le d\u00e9veloppement d'un syst\u00e8me de transport dans E. coli, une \u00e9volution et adaptation des polym\u00e9rases et la s\u00e9lection des produits vitaux.\nL'\u00e9quipe Xenome con\u00e7oit, construit et fait \u00e9voluer des micro-organismes dot\u00e9s de syst\u00e8mes g\u00e9n\u00e9tiques artificiels, dont l'information est port\u00e9e par les XNA. La prolif\u00e9ration et l'activit\u00e9 de ces organismes sont conditionn\u00e9es \u00e0 l'apport de XNAs, les pla\u00e7ant sous le contr\u00f4le strict de l'utilisateur.
The Xenome team designs, builds and evolves microorganisms with artificial genetic systems, whose information is carried by XNAs. The proliferation and activity of these organisms are conditioned to the supply of XNAs, placing them under the strict control of the user.<\/p>\n<\/div>\n<\/div>\n\n\n\n

Diversification des acides nucl\u00e9iques dans la nature<\/h2>\n\n\n\n
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Nous \u00e9tudions \u00e9galement la diversification des acides nucl\u00e9iques dans le monde vivant naturel, en nous concentrant sur les g\u00e9nomes de bact\u00e9riophages qui pr\u00e9sentent une grande diversit\u00e9 chimique de bases nucl\u00e9iques non canoniques. Certains virus infectant des h\u00f4tes tels que les prot\u00e9obact\u00e9ries, les cyanobact\u00e9ries et les actinobact\u00e9ries ont un g\u00e9nome \u00e0 ADN dans lequel l'ad\u00e9nine est compl\u00e8tement remplac\u00e9e par l'aminoad\u00e9nine (Z). L'\u00e9lucidation de la voie de biosynth\u00e8se de ce nucl\u00e9otide non canonique et la d\u00e9couverte des ADN polym\u00e9rases du bact\u00e9riophage DpoZ d\u00e9di\u00e9es \u00e0 l'incorporation de ce nucl\u00e9otide dans l'ADN ouvrent la voie \u00e0 la propagation de g\u00e9nomes chimiquement modifi\u00e9s chez les bact\u00e9ries (Pezo et al., Science 2021).Pezo et al.<\/em>, Science 2021<\/a>).<\/p>\n<\/div>\n<\/div>\n\n\n\n

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A _ Voie de synth\u00e8se du dZTP via des r\u00e9actions catalys\u00e9es par l'enzyme biosynth\u00e9tique PurZ cod\u00e9e par le phage et l'ADN polym\u00e9rase DpoZ. Les \u00e9tapes marqu\u00e9es \u00ab PurB \u00bb, \u00ab Gmk \u00bb et \u00ab Ndk \u00bb sont catalys\u00e9es par des enzymes de l'h\u00f4te bact\u00e9rien.\nB _ Profil HPLC de l'ADN phagique dig\u00e9r\u00e9. AU, unit\u00e9s arbitraires ; dC, d\u00e9soxycytidine ; dG, d\u00e9soxyguanosine ; dT, d\u00e9soxythymidine ; dZ, d\u00e9soxyaminoad\u00e9nosine ; dA, d\u00e9soxyad\u00e9nosine.\nFigures extraites de Pezo et al, Science 2021
B _ HPLC profile of phage DNA digested by nuclease and phosphatase. AU, arbitrary units; dC, deoxycytidine; dG, deoxyguanosine; dT, deoxythymidine; dZ, deoxyaminoadenosine; dA, deoxyadenosine.
Figures extracted from Pezo et al., <\/em>Science 2021<\/p>\n\n\n\n

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Since the natural genetic code of all life on our planet is recognized only as polymers of DNA and RNA, a robust approach is to develop a truly orthogonal nucleic acid, chemically distinct from DNA and RNA, but which can harbor structural and\/or sequence information essential to cell viability and phenotype. Such a Xenobiotic Nucleic Acids (XNA) will be genetically inert, and can only be taken over by artificial enzymes and synthesized from its xenonucleotide (XN) precursors. The latter, not being present in nature, must be chemically synthesized and explicitly supplied to the cell in order to survive. Such “safe” GMOs open new horizons for biotechnological and industrial applications; as non-natural life forms, they also contribute to a better understanding of natural organisms. XNAs in artificial systems Our objective is to develop an artificial information system based on a new type of nucleic acids that could function in vivo independently of the natural information system. To achieve this goal, four steps have to be elaborated: selection of the backbone chemistry, development of an uptake system in E. coli, evolution of polymerases and selection of vital products.The Xenome team designs, builds and evolves microorganisms with artificial genetic systems, whose information is carried by XNAs. The proliferation and activity of these organisms are conditioned to the supply of XNAs, placing them under the strict control of the user. Nucleic acids diversification in Nature We also study nucleic acid diversification in the natural living world, focusing on bacteriophage genomes that exhibit a high chemical diversity of non-canonical nucleic bases. Some viruses infecting hosts such as proteobacteria, cyanobacteria and actinobacteria have a DNA genome in which adenine is completely replaced by aminoadenine (Z). The elucidation of the biosynthetic pathway of this non-canonical nucleotide and the discovery of bacteriophage DpoZ DNA polymerases dedicated to the incorporation of this nucleotide into DNA pave the way for the propagation of chemically modified genomes in bacteria (Pezo et al., Science 2021). A _ Incorporation pathway of dZTP via reactions catalyzed by the phage-encoded biosynthetic enzyme PurZ and DNA polymerase DpoZ. The steps labeled \u201cPurB,\u201d \u201cGmk,\u201d and \u201cNdk\u201d are catalyzed by enzymes of the bacterial host.B _ HPLC profile of phage DNA digested by nuclease and phosphatase. AU, arbitrary units; dC, deoxycytidine; dG, deoxyguanosine; dT, deoxythymidine; dZ, deoxyaminoadenosine; dA, deoxyadenosine.Figures extracted from Pezo et al., Science 2021<\/p>","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-9","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/pages\/9","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/comments?post=9"}],"version-history":[{"count":26,"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/pages\/9\/revisions"}],"predecessor-version":[{"id":556,"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/pages\/9\/revisions\/556"}],"wp:attachment":[{"href":"https:\/\/xenome.genoscope.cns.fr\/fr\/wp-json\/wp\/v2\/media?parent=9"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}