The ability of natural biomaterials to shape, support, and orchestrate function inspire our efforts to produce functional materials. Guided by protein-based biomaterials, template-directed incorporation of synthetic building blocks can further expand biomaterial function by endowing new physical and biophysical properties. Here, I present the synthesis and applications of biomaterials that contain programmable combinations of natural and unnatural amino acids. Genomically recoded organisms were utilized to develop a genome-engineering based evolution platform for enzymes capable of multi-site incorporation of synthetic amino acids. This technology enabled the production of novel poly-fatty-acid biomaterials which can be used as carriers for improving peptide drug delivery. This work provides the basis for a new approach to template directed synthesis of biomaterials containing diverse synthetic chemical groups, with the goal of advancing our ability to analyze, mimic and manipulate biological systems.