Emerging molecular design principles of functional biomolecules and biomolecular assemblies
Professor, Takashi MORII
A transition to renewable energy technologies requires new chemistry to learn from nature. Nature has found fantastic solutions to convert solar energy to produce chemicals and to utilize them in the exceptionally efficient manners for almost 3 billion years. It is our challenge to understand the efficient bioenergetic processes of nature and to construct bio-inspired energy utilization systems. The research interests in our group focus on the design of biomacromolecules and their assemblies for molecular recognition, catalysis and signal transduction in water, the solvent of life. We take synthetic, organic chemical, biochemical and biophysical approaches to understand the biological molecular recognition and chemical reactions. Proteins and protein/nucleic acids assemblies are explored to realize biomimetic function of biological systems, such as visualization of cellular signals by fluorescent biosensors, directed self-assembly of peptides and proteins to build up nanobiomaterials, tailoring artificial receptors and enzymes based on the complex of RNA and a peptide or a protein, and reconstitution of the functional assemblies of receptors and enzymes on the nano architectures. Design strategies for receptors, sensors and enzymes are explored by utilizing structurally well-defined protein domains and protein-RNA complexes. Parallel application of the structure-based design and in vitro selection affords highly specific receptors and sensors for biologically important ligands, such as ATP and the phosphorylated tyrosine residue within a defined amino acid sequence. The information at the biological level, such as the dynamics of the ligand concentration changes, would be translated into a light signal by the fluorescent biosensors to understand the biological signal transduction mechanisms.
While the individual enzyme shows marvelous efficiency, the beauty of the chemical reaction processes in cells is found in its highly specific multi-step chemical transformation process in the presence of closely related ligands. Multiple enzymes cooperate to catalyze the sequential steps of chemical transformations in the efficiency that artificial catalysts still cannot achieve. A clue for such efficient sequential processes comes from the assembly of multiple enzymes. To realize such an assembly of enzymes or biomacromolecules, we use a DNA nanoarchitecture, DNA origami, for a template with defined addresses. Each unique address on the DNA origami will be used to locate a specific protein, RNA or RNP to generate an otherwise transitional assembly.