Engineering of Biomolecular Energy Conversion and Transport Modules for the Assembly of Molecular Factories

  • Schematic representation of a ‘simple’ biomolecular factory: The reactor is a nanocontainer (made of lipid or block copolymer) equipped with light-driven proton pumps (in red; energizing modules), proton-driven solute transporters (in blue; translocating modules) and metabolizing enzymes (in brown; metabolizing modules). Such light powered nanoreactors will import specific solutes from a solution and degrade them inside. Possible application: decontamination of water/solutions from toxic compounds or pollutant.
    Schematic representation of a ‘simple’ biomolecular factory: The reactor is a nanocontainer (made of lipid or block copolymer) equipped with light-driven proton pumps (in red; energizing modules), proton-driven solute transporters (in blue; translocating modules) and metabolizing enzymes (in brown; metabolizing modules). Such light powered nanoreactors will import specific solutes from a solution and degrade them inside. Possible application: decontamination of water/solutions from toxic compounds or pollutant.

Building autonomous synthetic organelles and cells with a defined function using a repertoire of functional modules (toolkit) and containing inside a minimal metabolism for survival, represents the ultimate goal of this project group.

Such complex processors will open a wide variety of possibilities ranging from environmental to medical applications. One of the most important challenges will be to provide a large repertoire of engineered and modular biomolecular-transport and -energy conversion systems for assembly of nanoreactors with diverse functionalities in lipid bilayers and block copolymers.

Initially, modules will include light-­driven proton pumps and proton-driven solute transporters in the membrane, and metabolizing enzymes inside the container. Next, more complex powering systems will be explored such as combinations of light-­driven proton pumps with sodium/proton antiporters with the objective: to energise sodium-driven solute transporters. This will significantly increase the repertoire and specificity of translocating modules.

The availability of numerous, highly specialized membrane proteins in milligram amounts offers the unique opportunity to use them as building blocks and toolkit to assemble molecular factories in the form of nanoreactors and functional surfaces using bottom-up approaches.

This project group has a strong expertise and knowledge in biochemistry, function and structure of membrane proteins. Furthermore, the group already possesses a significant number of recombinant transport proteins for different solutes such as peptides, sugars, amino acids and antibiotics that can be used as modules for engineering and assembly of nanoreactors.

Articles

R. Boggavarapu, J. Jeckelmann, D. Harder, Z. Ucurum, D. FotiadisRole of electrostatic interactions for ligand recognition and specificity of peptide transporters“ BMC Biology 13, 58 (2015). [Link] [More Information]
R. Petrosyan, C. A. Bippes, S. Walheim, D. Harder, D. Fotiadis, T. Schimmel, D. Alsteens, D. J. MüllerSingle-Molecule Force Spectroscopy of Membrane Proteins from Membranes Freely Spanning Across Nanoscopic Pores“ Nano Letters 15, 5, 3624-33 (2015). [Link]

Who works with whom?

Prof. Dimitrios Fotiadis from the University of Berne (Institute of Biochemistry and Molecular Medicine) leads this project and works in close collaboration with Stephan Hirschi and Mirko Stauffer (PhD-students).

Group

Read more about the Fotiadis-Group here.

Collaborations

Biophysical and structural characterization of engineered modules is being performed in collaboration with the groups of Daniel Müller and Gebhard Schertler, and assembly of modules into block copolymers in collaboration with Wolfgang Meier and Cornelia Palivan. Interactions with Urs Dürg and Sven Panke are and will be crucial for the development of functional surfaces and minimal metabolisms of nanocells, respectively. We are supporting with our expertise in membrane proteins projects from Richard Kammerer and Thomas Ward.