Structural biology of biosythetic enzymes

This group is located at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)

Natural agents have always been the best source of antibiotics. This is exemplified by success stories such as penicillin, streptomycin, erythromycin and rifamycin. But the potential of natural agents is not being tapped to the fullest extent yet. Often, this is related to the chemical synthesis being difficult and the yields of the purification of the agents from natural sources being low. Consequently, a large number of promising natural substances have been discovered, but were not developed further for clinical application, either because their chemical structure could not be changed sufficiently or because it was impossible to produce sufficient amounts of them.



Koehnke, J., Bent, A.F., Houssen, W.E., Mann, G., Jaspars, M. and Naismith, J.H. (2014): The structural biology of patellamide biosynthesis. Curr Opin Struct Biol. 29C, pp. 112-121 DOI: 10.1016/

Houssen, W.E., Bent, A.F., McEwan, A.R., Pieiller, N., Tabudravu, J., Koehnke, J., Mann, G., Adaba, R.I., Thomas, L., Hawas, U.W., Liu, H., Schwarz-Linek, U., Smith, M., Naismith, J.H. and Jaspars, M. (2014): An efficient method for the in vitro production of Azol(in)e-based cyclic peptides. Angew Chem Intl Ed Engl. 53(51), pp. 14171-4. DOI: 10.1002/anie.201408082

Mann, G., Koehnke, J., Bent, A.F., Graham, R., Houssen, W., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. (2014): The structure of the cyanobactin domain of unknown function from PatG in the patellamide gene cluster. Acta Cryst. F70(12), pp. 1597-603. DOI: 10.1107/S2053230X1402425X

Koehnke, J., Bent, A.F., Zollman, D., Smith, K., Houssen, W.E., Zhu, X., Mann, G., Lebl, T., Scharff, R., Shirran, S., Botting, C.H., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. (2013): The Cyanobactin Heterocyclase Enzyme: A Processive Adenylase That Operates with a Defined Order of Reaction. Angew Chem Int Ed Engl. 52(52), pp. 13991-6. DOI: 10.1002/anie.201306302

Bent, A.F., Koehnke, J., Houssen, W.E., Smith, M.C.M, Jaspars, M. and Naismith, J.H. (2013): Structure of PatF from Prochloron didemni. Acta Cryst. F69(6), pp. 618-23. DOI: 10.1107/S1744309113012931

Koehnke, J., Morawitz, F., Bent, A.F., Houssen, W.E., Shirran, S.L., Fuszard, M.A., Smellie, I.A., Botting, C.H. Smith, M.C., Jaspars, M. and Naismith, J.H. (2013): An Enzymatic Route to Selenazolines. Chembiochem. 14(5), pp. 564-7. DOI: 10.1002/cbic.201300037

Houssen, W.E.*, Koehnke, J.*, Zollman, D., Vendome, J., Raab, A., Smith, M.C., Naismith, J.H. and Jaspars, M. (2012): The Discovery of New Cyanobactins from Cyanothece PCC 7425 Defines a New Signature for Processing of Patellamides. Chembiochem. 13(18), pp 2683-9. DOI: 10.1002/cbic.201200661

Koehnke, J., Bent, A., Houssen, W.E., Zollman, D., Morawitz, F., Shirran, S., Vendome, J., Nneoyiegbe, A.F., Trembleau, L., Botting, C.H., Smith, M.C., Jaspars, M. and Naismith, J.H. (2012): The mechanism of patellamide macrocyclization revealed by the characterisation of the PatG macrocyclase domain. Nat Struct Mol Biol. 19(8), pp. 767-72. DOI: 10.1038/nsmb.2340

Koehnke, J., Katsamba, P.S., Ahlsen, G., Bahna, F., Vendome, J., Honig, B., Shapiro, L. and Jin, X. (2010): Splice form-dependence of β-neurexin/neuroligin binding interactions. Neuron 67(1): pp. 61-74. DOI: 10.1016/j.neuron

Koehnke, J., Jin, X., Budreck, E.C., Posy, S., Scheiffele, P., Honig, B. and Shapiro, L. (2008): Crystal structure of the extracellular cholinesterase-like domain from neuroligin-2. Proc Natl Acad Sci U S A. 105(6), pp. 1873-8. DOI: 10.1073/pnas.0711701105

Koehnke, J., Jin, X., Trbovic, N., Katsamba, P.S., Brasch, J., Ahlsen, G., Scheiffele, P., Honig, B., Palmer, A.G. 3rd and Shapiro, L. (2008): Crystal Structures of beta-Neurexin 1 and beta-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4. Structure. 16(3), pp 410-21. DOI: 10.1016/j.str

Jakobs, A.*, Koehnke, J.*, Himstedt, F., Funk, M., Korn, B., Gaestel, M. and Niedenthal, R. (2007): Ubc9 fusion-directed SUMOylation (UFDS): A method to analyze function of protein SUMOylation. Nature Methods. 4(3), pp. 245-250.

Hellenbroich, Y., Schulz-Schaeffer, W., Nitschke, M.F., Köhnke, J., Händler, G., Bürk, K., Schwinger, E. and Zühlke, C. (2004): Coincidence of a large SCA12 repeat allele with a case of Creutzfeld-Jacob disease. J Neurol Neurosurg Psychiatry 75(6): pp 937-8. DOI: 10.1136/jnnp.2003.028381

* = equal contribution


  • Dr Jesko Köhnke


    Head of Junior Research Group Structural biology of biosynthetic enzymes

    +49 681 98806-3500