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Building biomaterials through genetic code expansion

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TRENDS IN BIOTECHNOLOGY
卷 41, 期 2, 页码 165-183

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CELL PRESS
DOI: 10.1016/j.tibtech.2022.07.003

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Genetic code expansion allows the incorporation of noncoded amino acids (NCAAs) and unnatural amino acids (UNAAs) into engineered proteins, providing them with dedicated structure and function. This method has the potential to produce biomaterials with NCAAs/UNAAs that mimic natural matrix-cell interactions, which is important for tissue engineering. Codon suppression and reassignment globally introduce NCAAs/UNAAs, enabling the design of biomaterials with growth factor mimetics called catechols that modulate cell-matrix interactions. This protein engineering approach can lead to tunable biomaterials that are tissue-specific and compliant.
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 posttranslational 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.

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