We study the molecular mechanisms of light sensing, transmembrane conductance, and adhesion. For example, structures of class I and II photolyases complexed to UV-damaged DNA showed that repair of genotoxic UV-lesions depends on the UV/blue light-driven injection of an electron onto the lesion when it is bound next to the flavin chromophore. Our work on cyanobacterial phytochromes proved that red-light signaling, exerted e. g. by plants, employs a complex environment for controlling the photoreactivity of their bilin chromophore. Based on our structural and biochemical data we engineer novel optogenetic tools for exerting light-control on signaling, gene expression, or catalysis.
Other projects address fungal cell wall architecture & adhesion, which are relevant for human health or biotechnology. Finally, structure-based ion-channel engineering of membrane proteins of the porin-superfamily will create synthetic transporters with predefined specificity, e. g. as components of biosensors.
Flavoproteins play numerous roles in catalysis and photoreception. Concerning the latter several families of flavin-based photoreceptors such as the DNA-photolyases/cryptochromes, the BLUF- and the LOV-domains have been hitherto characterized. Manipulating the chemical nature of the flavin chromophores bears the prospect to produce photoreceptors with novel spectral sensitivity and signaling characteristics. So far, several strategies to utilize synthetic flavin analogs have been devised for their incorporation into apoproteins, either in vitro as exemplified for native DNA-photolyases (Klar et al., 2006) and refolded BLUF domains (Schroeder et al., 2008) or in vivo as shown for LOV domains and dodecins (Mathes et al., 2009).
Our SYNMIKRO project establishes a novel biosynthesis pathway for deazaflavin-based FAD analogs to engineer photolyases and other flavoproteins with altered catalytic and photosensory properties, respectively.