Structural Biology of Biosynthetic Enzymes
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.
Sikandar A, Cirnski K, Testolin G, Volz C, Brönstrup M, Kalinina O V, Müller R, Koehnke J (2018): Adaptation of a Bacterial Multidrug Resistance System Revealed by the Structure and Function of AlbA. J Am Chem Soc. DOI: 10.1021/jacs.8b08895
Franz L, Adam S, Santos-Aberturas J, Truman AW, Köhnke J (2017): Macroamidine formation in bottromycins is catalyzed by a divergent YcaO enzyme. J Am Chem Soc. DOI: 10.1021/jacs.7b09898
Fu, C., Sikandar, A., Donner, J., Zaburannyi, N., Herrmann, J., Reck, M., Wagner-Döbler, I.+, Köhnke J.+ and Müller, R.+ (2017): The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD. Nat Comm DOI:10.1038/s41467-017-01671-5
Beshr, G., Sikandar, A., Jemiller, E.M., Klymiuk, N., Hauck, D., Wagner, S., Wolf, E., Köhnke, J.+ and Titz, A.+ (2017) Photorhabdus luminescens lectin A (PllA)-a new probe for detecting α-galactoside-terminating glycoconjugates. J Biol Chem DOI:10.1074/jbc.M117.812792
Mann, G., Huo, L., Adam, S., Nardone, B., Vendome, J., Westwood, N.J., Müller, R. and Köhnke, J. (2016): Structure and substrate recognition of the Bottromycin maturation enzyme BotP. Chembiochem, 17(23), pp. 2286-92.