Synthetic biology and antibiotic research

The mission of the Link Lab is to advance knowledge and innovation in synthetic biology and antibiotic research, addressing two global challenges: sustainable production of chemicals and combating antibiotic resistance.

In the realm of antibiotic research, we investigate how bacterial metabolism influences the effectiveness of antibiotics. Through the integration of genomics, proteomics, and metabolomics, we map and explore the mechanisms of antibiotic resistance and antibiotic killing in three of the most critical pathogenic bacteria: E. coli, S. aureus and P. aeruginosa.

In synthetic biology, our objective is to engineer bacterial metabolism for a sustainable bioeconomy by producing chemicals with non-growing bacteria. Therefore, we employ innovative techniques such as synthetic feedback regulation, thermo-switches and real-time metabolomics to control the growth and overproduction of chemicals in engineered bacteria. Moreover, we aim to utilize synthetic CO₂-fixation to access sustainable feedstocks for chemical production.

Prof. Dr. Hannes Link

Head of the research group

Hannes Link is a W3 Professor and leads the Bacterial Metabolomics Group at the University of Tübingen. Previously, he served as an Independent Research Group at the Max Planck Institute for Terrestrial Microbiology in Marburg (Germany), and was a Postdoctoral Associate in the Uwe Sauer Lab at the Institute of Molecular Systems Biology, ETH Zurich (Switzerland). Hannes Link holds a Ph.D. in Biochemical Engineering from the Technical University Munich, Germany. His doctoral research focused on "Metabolic control analysis of bioprocesses" under the supervision of Prof. Dirk Weuster-Botz. He also holds a Diploma in Chemical Engineering from the same university. He received an ERC Starting Grant for the MapMe project, which aimed to map metabolic regulators at a genome-scale, as well as a DFG Emmy Noether Fellowship, focusing on bioprocess engineering through dynamic control of metabolic pathways.

Board member of the Cluster of Excellence “Controlling microbes to fight infections”, University of Tübingen, Germany
Co-director of the Interfaculty Institute for Microbiology and Infection Medicine
Steering Committee of the Synthetic Biology Work Group of the DECHEMA
Scientific Advisory Board, The German Association for Synthetic Biology (GASB)

Selected publications

map

mechanisms of antibiotic resistance

CO2

-fixation

engineer

bacterial metabolism

Selected publications

Lubrano P., Smollich F., Schramm T., Lorenz E., Alvarado A., Eigenmann S. C., Stadelmann A., Thavapalan S., Waffenschmidt N., Glatter T., Hoffmann N., Müller J., Peter S., Drescher K., Link H. (2025) Metabolic mutations reduce antibiotic susceptibility of E. coli by pathway-specific bottlenecks. Mol Syst Biol.
https://doi.org/10.1038/s44320-024-00084-z
Pahl V., Lubrano P., Troßmann F. , Petras D. , Link H. (2024) Intact protein barcoding enables one-shot identification of CRISPRi strains and their metabolic state. Cell Reports Methods.
https://doi.org/10.1016/j.crmeth.2024.100908
Wang CY, Lempp M, Farke N, Donati S, Glatter T, Link H (2021) Metabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli. Nature Communications.
https://doi.org/10.1038/s41467-021-25142-0
Donati S, Kuntz M, Pahl V, Farke N, Beuter D, Glatter T, Gomes-Filho JV, Randau L, Link H (2021) Multi-omics analysis of CRISPRi-knockdowns identifies mechanisms that buffer decreases of enzymes in E. coli metabolism. Cell Systems.
https://doi.org/10.1016/j.cels.2020.10.011
Schramm T, Lempp M, Beuter D, Sierra SG, Glatter T, Link H (2020) High-throughput enrichment of temperature-sensitive argininosuccinate synthetase for two-stage citrulline production in E. coli. Metabolic Engineering.
https://doi.org/10.1016/j.ymben.2020.03.004
Lempp M, Farke N, Kuntz M, Freibert S, Lill R, Link H (2019) Systematic identification of metabolites controlling gene expression in E. coli. Nature Communications.
https://doi.org/10.1038/s41467-019-12474-1
Sander T, Farke N, Diehl C, Kuntz M, Glatter T, Link H (2019) Allosteric feedback inhibition enables robust amino acid biosynthesis in E. coli by enforcing enzyme overabundance. Cell Systems.
https://doi.org/10.1016/j.cels.2018.12.005

The M3 Research Center
Malignome, Metabolome and Microbiome