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MapMe SIGNED

Mapping metabolic regulators at a genome-scale to switch bacteria from growth to overproduction of chemicals

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

MapMe project word cloud

Explore the words cloud of the MapMe project. It provides you a very rough idea of what is the project "MapMe" about.

metabolomics crispr functionally genome gt creates lack gene metabolites induction exploration rarely of metabolic perturbations guided model data single prediction proteins grounds prohibits superior metabolite acid coli microbe escherichia uncoupling quantitatively rational modifications perturb mediated strains regulatory infer biotechnology endeavor interactions protein small consequence date overproduction genes unknown network succinic roles previously opens substantially industrial indirect purpose centres map severely combining basis relationships break systematic entire interference limited microbes predict productivity unrelated distal models synthesis cease engineering 900

Project "MapMe" data sheet

The following table provides information about the project.

Coordinator	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: Munich postcode: 80539 website: www.mpg.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	1˙461˙200 €
EC max contribution	1˙461˙200 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-STG
Funding Scheme	ERC-STG
Starting year	2017
Duration (year-month-day)	from 2017-01-01 to 2021-12-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: Munich postcode: 80539 website: www.mpg.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (Munich)	coordinator	1˙461˙200.00

Map

Project objective

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.

Publications

List of publications.
year	authors and title	journal	last update
2019	Simon Boecker, Ahmed Zahoor, Thorben Schramm, Hannes Link, Steffen Klamt Broadening the Scope of Enforced ATP Wasting as a Tool for Metabolic Engineering in Escherichia coli published pages: 1800438, ISSN: 1860-6768, DOI: 10.1002/biot.201800438	Biotechnology Journal	2019-08-29
2019	Timur Sander, Niklas Farke, Christoph Diehl, Michelle Kuntz, Timo Glatter, Hannes Link Allosteric Feedback Inhibition Enables Robust Amino Acid Biosynthesis in E.Â coli by Enforcing Enzyme Overabundance published pages: 66-75.e8, ISSN: 2405-4712, DOI: 10.1016/j.cels.2018.12.005	Cell Systems 8/1	2019-08-29

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