Obiettivo Metabolic engineering creates improved microbes for industrial biotechnology. Rational design of industrial microbes centres on modifications of genes with known roles in the production pathway of interest. However, genes that are unrelated to the production pathway are also known to substantially impact productivity. To date there are no methods that allow the prediction of such distal genes on a rational basis. Effects of distal genes are indirect, and mediated through regulatory interactions between metabolites and proteins, most of which are currently unknown even in the well-studied microbe Escherichia coli. The lack of knowledge of metabolite-protein interactions thus effectively prohibits systematic exploration of distal regulatory relationships, with the consequence that models used to predict metabolic engineering targets are severely limited and rarely applied in industrial biotechnology. Previously, we used small-scale metabolic models and metabolomics to infer metabolite-protein interactions in specific pathways. In this project we propose a novel genome-wide endeavor to map metabolite-protein interactions across the entire metabolic network. For this purpose, we will use the recently developed CRISPR interference system to quantitatively perturb >900 single metabolic genes in E. coli. Combining the metabolomics data of these >900 gene perturbations with a genome-scale metabolic model will enable us to infer functionally relevant metabolite-protein interactions. Finally, we will apply this knowledge to the model-guided metabolic engineering of superior E. coli strains. Specifically, we want E. coli to cease growth upon induction and focus all its metabolic resources towards synthesis of succinic acid. This controlled uncoupling of growth from overproduction on a rational basis will break new grounds in metabolic engineering and opens up novel applications in industrial biotechnology. Campo scientifico engineering and technologyindustrial biotechnologymetabolic engineeringnatural scienceschemical sciencesorganic chemistryaminesnatural sciencescomputer and information sciencesartificial intelligencemachine learningnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencescomputer and information sciencesartificial intelligencecomputational intelligence Parole chiave MapMe Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-STG - ERC Starting Grant Invito a presentare proposte ERC-2016-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Istituzione ospitante EBERHARD KARLS UNIVERSITAET TUEBINGEN Contribution nette de l'UE € 706 177,77 Indirizzo GESCHWISTER-SCHOLL-PLATZ 72074 Tuebingen Germania Mostra sulla mappa Regione Baden-Württemberg Tübingen Tübingen, Landkreis Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 706 177,77 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto EBERHARD KARLS UNIVERSITAET TUEBINGEN Germania Contribution nette de l'UE € 706 177,77 Indirizzo GESCHWISTER-SCHOLL-PLATZ 72074 Tuebingen Mostra sulla mappa Regione Baden-Württemberg Tübingen Tübingen, Landkreis Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 706 177,77 MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Partecipazione conclusa Germania Contribution nette de l'UE € 755 022,23 Indirizzo HOFGARTENSTRASSE 8 80539 Munchen Mostra sulla mappa Regione Bayern Oberbayern München, Kreisfreie Stadt Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 755 022,23