{"id":13864,"date":"2023-11-23T07:20:00","date_gmt":"2023-11-23T06:20:00","guid":{"rendered":"https:\/\/www.toulouse-biotechnology-institute.fr\/?p=13864"},"modified":"2023-11-23T11:21:17","modified_gmt":"2023-11-23T10:21:17","slug":"soutenance-de-these-thibault-malfoy","status":"publish","type":"post","link":"https:\/\/www.toulouse-biotechnology-institute.fr\/en\/soutenance-de-these-thibault-malfoy\/","title":{"rendered":"PhD Defence Thibault Malfoy"},"content":{"rendered":"<p class=\"wp-block-paragraph\">Soutenance de th\u00e8se de doctorat le <strong>4 d\u00e9cembre 2023 \u00e0 14h en salle 401<\/strong>.<br><br>La th\u00e8se s&rsquo;intitule : \u00ab\u00a0La promiscuit\u00e9 de prot\u00e9ines : facteur clef pour la (r\u00e9-)assimilation et la valorisation de la mol\u00e9cule plateforme non naturelle 2,4-dihydroxybutyrate chez <em>Escherichia coli<\/em>\u00ab\u00a0.<br><br>Le jury sera compos\u00e9 de Jean Marie Fran\u00e7ois (Directeur de th\u00e8se), St\u00e9phanie Heux (Examinatrice), Marie-Th\u00e9r\u00e8se Giudici-Orticoni (Rapporteure) et Alain Perret (Rapporteur). Vous trouverez ci-apr\u00e8s un r\u00e9sum\u00e9 de ma th\u00e8se :<br><br>Les mol\u00e9cules plateformes sont des petites mol\u00e9cules faisant l&rsquo;interface, dans la production de produits de commodit\u00e9, entre une source de carbone (fossile ou renouvelable) et ces produits. La production de ces mol\u00e9cules en biotechnologie a tendance \u00e0 devenir une part importante des mol\u00e9cules plateformes en raison de la volont\u00e9 de d\u00e9velopper la bio\u00e9conomie circulaire, en utilisant des sources de carbone renouvelable, et en produisant des mol\u00e9cules moins compromettantes pour l&rsquo;environnement, particuli\u00e8rement dans le domaine des plastiques. Le 2,4-dihydroxybutyrate (DHB) est un exemple de ce type de mol\u00e9cule plateforme originale, car d\u2019une part, cette mol\u00e9cule n\u2019est pas produite naturellement par les micro-organismes, et d\u2019autre part, elle peut permettre la confection de mol\u00e9cules dans les secteurs de la chimie fine et de commodit\u00e9 (1,3-propanediol et acide hydroxypropionique, et pr\u00e9curseurs pour de nouveaux biopolym\u00e8res), de la pharmacie (2-butyrolactone, butanetriol) et de la nutrition animale (d\u00e9riv\u00e9 de la m\u00e9thionine). Cependant, sa production doit \u00eatre industriellement attractive, ce qui a \u00e9t\u00e9 l\u2019objet de nombreux travaux qui ont \u00e9t\u00e9 r\u00e9alis\u00e9s ant\u00e9rieurement \u00e0 ma th\u00e8se et qui sont encore en cours actuellement.<br>DHB is not a naturally occurring molecule in its production host organism <em>Escherichia coli, <\/em>ce qui signifie qu&rsquo;\u00e0 part quelques promiscuit\u00e9s de substrat ayant \u00e9t\u00e9 envisag\u00e9es pour la production du DHB ou l&rsquo;am\u00e9lioration de souches\u00a0 productrices, il n&rsquo;existe pas de description de l&rsquo;interaction du DHB avec la physiologie d&rsquo;<em>E. coli<\/em>. Mon travail de th\u00e8se a donc contribu\u00e9 \u00e0 l&rsquo;annotation des voies m\u00e9taboliques permettant l&rsquo;assimilation du DHB. Par l&rsquo;ajout d&rsquo;un rac\u00e9mique de DHB dans le milieu, il a \u00e9t\u00e9 constat\u00e9 que le DHB peut \u00eatre oxyd\u00e9 par trois lactates oxydases d&rsquo;<em>E. coli<\/em>, et produire le 2-oxo-4-hydroxybutyrate (OHB), qui s&rsquo;av\u00e8re \u00eatre le pr\u00e9curseur de DHB dans certaines voies con\u00e7ues pour sa biosynth\u00e8se. L&rsquo;OHB peut ensuite \u00eatre cliv\u00e9 en formald\u00e9hyde et en pyruvate par plusieurs aldolases pyruvate sp\u00e9cifiques, respectivement dissimil\u00e9 en formate et pyruvate, lequel peut se voir redirig\u00e9 vers le m\u00e9tabolisme carbon\u00e9 central des cellules. Ce projet a \u00e9galement permis de mettre en \u00e9vidence de potentiels importeurs de DHB.<br>En parall\u00e8le, la construction d&rsquo;un biosenseur d&rsquo;OHB a \u00e9t\u00e9 effectu\u00e9e, et son utilisation dans diverses applications d\u00e9montr\u00e9es. Enfin, la possibilit\u00e9 d&rsquo;utiliser le DHB comme monom\u00e8re pour la biosynth\u00e8se d&rsquo;un polym\u00e8re innovant a \u00e9galement \u00e9t\u00e9 \u00e9tudi\u00e9e dans ce travail. Pr\u00e9liminairement \u00e0 cet aspect, la contrainte pour l&rsquo;enzyme catalysant la polym\u00e9risation d\u2019utiliser l\u2019\u00e9nantiom\u00e8re (D) du substrat a n\u00e9cessit\u00e9 l&rsquo;identification d&rsquo;une enzyme catalysant la r\u00e9duction de l&rsquo;OHB vers le D-DHB. Bien que d&rsquo;autres voies d&rsquo;assimilation du DHB restent encore \u00e0 \u00eatre d\u00e9termin\u00e9es, et que la synth\u00e8se de polym\u00e8re n\u00e9cessite encore du travail, tous ces r\u00e9sultats soutiennent le fait que la promiscuit\u00e9 de substrat des prot\u00e9ines (enzymes, facteur de transcription, transporteur) d&rsquo;E. coli est importante. Elle permet la facilitation de la mise en place de nouvelles voies synth\u00e9tique de production de mol\u00e9cules. Mais dans le m\u00eame temps, la production de mol\u00e9cules, et a fortiori non naturelles, requiert une attention particuli\u00e8re pour \u00e9viter des interactions ind\u00e9sirables, possiblement d\u00e9l\u00e9t\u00e8res ou toxiques pour les cellules, pouvant p\u00e9naliser significativement sa \u00ab production \u00bb par l\u2019usine cellulaire ainsi construite.<\/p>","protected":false},"excerpt":{"rendered":"<p>December 4th, 2023<\/p>","protected":false},"author":1,"featured_media":13865,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10,75],"tags":[72],"class_list":["post-13864","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-evenement","category-soutenance","tag-equipe-phyge"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Soutenance de th\u00e8se 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