Genomically Recoded Organisms—Living Foundries for Producing Programmable Biomaterials

Materials produced from synthetic chemical processes provide access to a broad range of chemical structures yet are constrained by the lack of sequence-defined polymerization methods. In contrast, biological systems employ sequence-controlled processes to synthesize biomolecules, in which the molecular information encoded by nucleic acids is converted into sequence-controlled protein polymers. However, nature is constrained to a small set of organic monomeric building blocks, the 20 canonical amino acids, thereby limiting the chemical diversity of polymeric biomaterials. Advances in synthetic biology permit the genetic encoding of synthetic chemistries at monomeric precision, enabling the synthesis of programmable proteins with tunable properties. Here, I describe the design and construction of genomically recoded organisms (GROs) possessing open coding challenges. These open codons, together with engineered translation machinery, enable site-specific and multi-site nsAA incorporation in proteins at high yields and purity where multiple identical nsAAs provide the dominant chemical and biophysical properties to proteins or biopolymers. Finally, I will describe the production of sequence-defined biomaterials with applications in highly-conductive protein nanowires and functionalized biotherapeutics. The use of GROs to produce multifunctional, structurally complex materials can be expanded toward the development of a programmable new class of genetically encoded biomaterials with diverse chemistries and broad applications for new classes of enzymes, materials, and therapeutics.