Protein Tectons in Synthetic Biology

Abstract

The expansion of cellular functions via novel modular building blocks, namely unnatural amino acids, their site-selective genetically encoded cotranslational incorporation into proteins, requires the redesign and expansion of the translational network with additional components, the orthogonal tRNA and tRNA synthetase. At the next level protein tectons (tecton = architectural building block) constitute complex genetically encoded "material libraries" inside the cell. These protein tectons are architectural building blocks allowing for complex supramolecular self-assembly inside the cell, forming cellular compartments or constituting 3D matrix mimicry of the extracellular matrix outside the cell. In addition they form the basis for biohybrid materials in protein/enzyme engineering, nanotechnology and regenerative medicine. The defined modification of protein tectons utilizing chemical biology allows for the selective bioconjugation e.g. of unnatural amino acids, via bioorthogonal chemical reactions introducing novel chemical entities expanding the repertoire of "posttranslational" protein modifications in vitro and in vivo for various applications.