Semi-synthetic Biomaterial Production Enabled by Multi-site Incorporation of Unnatural Amino Acids in Protein-Polymers

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1Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University, Beer-Sheva, Israel
2Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA
3Department of Biomedical Engineering, Yale University, New Haven, CT, USA

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.









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