Building biomaterials through genetic code expansion.

Genetic code expansion (GCE) enables directed incorporation of noncoded amino acids (NCAAs) and unnatural amino acids (UNAAs) into the active core that confers dedicated structure and function to engineered proteins. Many protein biomaterials are tandem repeats that intrinsically include NCAAs generated through post-translational modifications (PTMs) to execute assigned functions. Conventional genetic engineering approaches using prokaryotic systems have limited ability to biosynthesize functionally active biomaterials with NCAAs/UNAAs. Codon suppression and reassignment introduce NCAAs/UNAAs globally, allowing engineered proteins to be redesigned to mimic natural matrix-cell interactions for tissue engineering. Expanding the genetic code enables the engineering of biomaterials with catechols - growth factor mimetics that modulate cell-matrix interactions - thereby facilitating tissue-specific expression of genes and proteins. This method of protein engineering shows promise in achieving tissue-informed, tissue-compliant tunable biomaterials.