Lars-Oliver Essen

Lars-Oliver Essen

Prof. Dr. Lars-Oliver Essen

Chemistry
Structural Biochemistry
Hans-Meerwein-Straße 4, 35032 Marburg
+49-6421 28 22032
essen@chemie.uni-marburg.de
http://www.uni-marburg.de/fb15/ag-essen

 

Research area

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.

Figure 1: The first crystal structure of a class II photolyase (left) shows that this type of photolyase occurring in higher eukaryotes and some prokaryotes has numerous differences to microbial class I photolyases despite a common architecture. Pathway engineering for biosynthesis of 8-hydroxy-deazaflavin (8-HDF) in Escherichia coli facilitated the structural analysis of a complex of this recombinant DNA repair enzyme with its cognate light antenna 8-HDF (right).Figure 1: The first crystal structure of a class II photolyase (left) shows that this type of photolyase occurring in higher eukaryotes and some prokaryotes has numerous differences to microbial class I photolyases despite a common architecture. Pathway engineering for biosynthesis of 8-hydroxy-deazaflavin (8-HDF) in Escherichia coli facilitated the structural analysis of a complex of this recombinant DNA repair enzyme with its cognate light antenna 8-HDF (right).
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.

  Figure 2: Adhesion domains of cell wall proteins from baker’s yeast (A, Flo5A) and the human pathogen Candida glabrata (B, Epa1). The Flo5A domain on the left plays an eminent role in controlling yeast flocculation which controls e. g. the formation of yeast flocs during fermentation in the brewery industry. In contrast, the homologous adhesin from C. glabrata allows this Candida species to colonize human epithelia and invade patients under intense-care conditions via catheter materials.

Research project within SYNMIKRO

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.

Figure 3: Ion-channel engineering as exemplified on the monomeric OmpG porin from Escherichia coli. Different chemical strategies like S-alkylation (shown on the left) or native chemical ligation can be used for constructing hybrid ion channels. The OmpG hybrid on the right was analyzed by electrophysiology and structural analysis. Figure 3: Ion-channel engineering as exemplified on the monomeric OmpG porin from Escherichia coli. Different chemical strategies like S-alkylation (shown on the left) or native chemical ligation can be used for constructing hybrid ion channels. The OmpG hybrid on the right was analyzed by electrophysiology and structural analysis.

SYNMIKRO Young Researchers Groups

Almost all scientific members of SYNMIKRO are actively involved in DFG’s Collaborative Research Centers (Sonderforschungsbereiche), Research Training Groups (Graduiertenkollegs), or other Cooperative Research projects. Alongside performing adventurous experiments, and reporting excellent science, SYNMIKRO substantially promotes potential Young Research Group Leaders by constantly keeping its doors open to welcome and support Young Researchers planning to set up an Independent Research Group.
Our Young Research Groups