Unnatural amino acids in enzymes and proteins

It is an intriguing question whether the proteins and enzymes could harbor the unnatural amino acid analogues and retain their activity. The present report reviews the published data on the enzymes harboring unnatural amino acids and presents the experimental results demonstrating the phenomenon of the cellsʹ normal growth even if a substantial part of one amino acid is substituted by its element-organic analogue. ne phosphatase, aspartate transcarbamylase, β-lactamase, T4 lisozyme and glutathione transferase containing various unnatural amino acids are reviewed in this report. ast cell growth in the presence of 4-fluorophenylalanine (FPA), being the element-organic unnatural amino acid, has been studied and the analogue content in the total cell protein determined. A significant part (35–40%) of phenylalanine was found to be replaced by FPA and the cells continued to function normally. FPA-resistant phenotype capable of growing in FPA presence has also been selected. The FPA content in the protein of the resistant strain has also been determined and it was found that 30–40% of phenylalanine was replaced by FPA.