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Research

Research interests of the AG Teufel

The Teufel laboratory provides an excellent opportunity for students who wish to explore microbial secondary metabolic pathways and exceptional enzymatic reactions that give rise to pharmaceutically relevant natural products. Our studies currently mainly aim to unveil novel flavin-dependent enzyme reactions that play pivotal roles in the generation of structurally complex pharmacophores. The importance of the flavin cofactor for countless redox reactions was recognized long ago, albeit mechanistic studies were heavily focused on a moderate assortment of primary metabolic flavoenzymes. While this granted deep insight into many aspects of flavin-dependent catalysis, the more recent detailed biochemical characterization of secondary metabolic pathways has proven a true treasure trove for flavin enzymology and unearthed a broader catalytic diversity. It appears that the unmatched versatility of flavoenzymes is ideally suited for secondary metabolism, nature’s biosynthetic tinkering ground, and significantly contributes to the vast chemical and functional diversity of natural products such as antibiotics or anticancer agents.

Figure: Active site of the flavoenzyme EncM (left panel) that catalyzes an unprecedented oxidation reaction (right panel) during polyketide antibiotic biosynthesis.1-4,6

For detailed information about our research program or to inquire about open positions, please contact Dr. Robin Teufel (E-mail: robin.teufel@zbsa.de).
 

Selected Publications: 

  1. Duan, Y., Petzold, M., Saleem-Batcha, R. & Teufel, R. Bacterial Tropone Natural Products and Derivatives: Overview of their Biosynthesis, Bioactivities, Ecological Role and Biotechnological Potential. Chembiochem 10.1002/cbic.201900786 (2020).
  2. Matthews, A., Saleem-Batcha, R., Sanders, J. N., Stull, F., Houk, K. N. & Teufel, R. Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases. Nature Chemical Biology 30, 175; 10.1038/s41589-020-0476-2 (2020).
  3. Spieker, M., Saleem-Batcha, R. & Teufel, R. Structural and Mechanistic Basis of an Oxepin-CoA Forming Isomerase in Bacterial Primary and Secondary Metabolism. ACS Chemical Biology 14, 2876–2886; 10.1021/acschembio.9b00742 (2019).
  4. Saleem-Batcha, R., Stull, F., Sanders, J. N., Moore, B. S., Palfey, B. A., Houk, K. N. & Teufel, R. Enzymatic Control of Dioxygen Binding and Functionalization of the Flavin Cofactor. Proceedings of the National Academy of Sciences of the United States of America 115, 4909–4914; 10.1073/pnas.1801189115 (2018).
  5. Teufel, R. Flavin-catalyzed Redox Tailoring Reactions in Natural Product Biosynthesis. Archives of Biochemistry and Biophysics 632, 20–27; 10.1016/j.abb.2017.06.008 (2017).
  6. Teufel, R., Agarwal, V. & Moore, B. S. Unusual Flavoenzyme Catalysis in Marine Bacteria. Current Opinion in Chemical Biology 31, 31–39; 10.1016/j.cbpa.2016.01.001 (2016).
  7. Teufel, R., Stull, F., Meehan, M. J., Michaudel, Q., Dorrestein, P. C., Palfey, B. & Moore, B. S. Biochemical Establishment and Characterization of EncM's Flavin-N5-oxide Cofactor. Journal of the American Chemical Society 137, 8078–8085; 10.1021/jacs.5b03983 (2015).
  8. Teufel, R., Kaysser, L., Villaume, M. T., Diethelm, S., Carbullido, M. K., Baran, P. S. & Moore, B. S. One-Pot Enzymatic Synthesis of Merochlorin A and B. Angewandte Chemie (International ed. in English) 53, 11019–11022; 10.1002/anie.201405694 (2014).
  9. Teufel, R., Miyanaga, A., Michaudel, Q., Stull, F., Louie, G., Noel, J. P., Baran, P. S., Palfey, B. & Moore, B. S. Flavin-mediated Dual Oxidation Controls an Enzymatic Favorskii-Type Rearrangement. Nature 503, 552–556; 10.1038/nature12643 (2013).
 
Funding:
  • DFG grants TE 931/2-1 (Emmy Noether), & TE 931/3-1 (Sachbeihilfe), TE 931/4-1 (Heisenberg)
  • Research Seed Capital – RiSC Ministry of Science, Research and the Arts of Baden-Württemberg (MWK) (AZ: 7532.21/2.1.6)
  • „Innovationsfonds Forschung“ of the University Freiburg
  • DFG-Research Training Group (RTG) 1976: Functional Diversity of Cofactors in Enzymes

 

Contact

Center for Biological Systems Analysis

University of Freiburg

 

  • Address:

    Habsburgerstr. 49
    79104 Freiburg
    Germany
 
  • Delivery entrance:

    Hauptstr. 1
    79104 Freiburg
 

 

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