Novel Enzymatic Reactions in Bacterial Secondary Metabolism
The Teufel group investigates the enzymatic formation of complex pharmacophores from bacterial natural products, with a current focus on flavin-dependent redox enzymes. Our research program lies at the interface of chemistry & biology and comprises a variety of methods, e.g., protein biochemistry/crystallography, molecular biology/genetics, chemoenzymatic total synthesis, in vitro and in vivo biochemical analysis, chemical synthesis, analytical chemistry (e.g., HPLC-MS, NMR & UV-Vis spectroscopy), synthetic biology, and metabolomics.
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 diversity of natural products via functionalization (e.g., halogenation, hydroxylation) or substrate activation reactions (e.g. dehydrogenation). Our studies aim to unveil novel flavin-dependent enzyme reactions that play pivotal roles in the generation of structurally unique pharmacophores.
Figure: Active site of the flavoenzyme EncM (left panel) that catalyzes an unprecedented oxidation reaction (right panel) during polyketide antibiotic biosynthesis.1,2
The newly established Teufel laboratory provides an excellent opportunity for students who wish to explore microbial metabolic pathways and exceptional enzymatic reactions that give rise to pharmaceutically relevant chemical compounds. For detailed information about our research program or to inquire about open positions, please contact Dr. Robin Teufel (E-mail: firstname.lastname@example.org).
- Teufel R., Kaysser L., Villaume MT., Diethelm S., Carbullido MK., Baran PS., & Moore BS. One-pot enzymatic synthesis of merochlorin A and B. Angew Chem Int Ed 53, 11019-22 (2014).
- Teufel R., Miyanaga A., Michaudel Q., Stull F., Louie G., Noel JP., Baran PS., Palfey B., & Moore BS. Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Nature 503, 552-6 (2013).
- Teufel R., Friedrich T., & Fuchs G. An oxygenase that forms and deoxygenates toxic epoxide. Nature 483, 359-62 (2012).
- Teufel R., Mascaraque V., Ismail W., Voss M., Perera J., Eisenreich W., Haehnel W., & Fuchs G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc Natl Acad Sci U S A 107, 14390-5 (2010).
- DFG-Emmy Noether Programme (TE 931/2-1)
- 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