Repurposing the translation apparatus for synthetic biology

The translation apparatus is the cell?s factory for protein synthesis, stitching together amino acid substrates into sequence-controlled polymers (proteins) from a defined template. With protein synthesis rates of up to 20 amino acids per second at an accuracy of 99.99%, the extraordinary catalytic capacity of the translation machinery has attracted extensive efforts to repurpose it for biochemical engineering applications. In this presentation, I will discuss our efforts to develop enabling technologies for understanding, harnessing, and expanding the capabilities of the translation apparatus. In one example, we seek to create a new paradigm for engineering the protein synthesis machinery using cell-free synthetic biology. The foundational principle is that we can conduct precise, complex biomolecular transformations in crude lysates without using intact cells, which provides an unprecedented freedom of design and control. In another example, we have created the first fully orthogonal ribosome?mRNA system in cells where mRNA decoding, catalysis of polypeptide synthesis, and protein excretion can be optimized for new substrates and functions. Our work provides exciting new opportunities to monitor, interrogate, and understand the process of translation, and with this knowledge diversify, evolve and repurpose the ribosome and its peripheral machinery into a re-engineered machine to generate non-natural polymers as new classes of sequence-defined, evolvable matter.