Proteins are ubiquitous biomolecules which are essential for crucial functions in a majority of biological processes. Essentially, they are comprised of 20 standard amino acids, the sequence of which is encoded in the genetic code. But it is possible to include some amino acids beyond the canonical 20 amino acids by incorporating bioorthogonal functional groups into proteins. Thus, incorporation of noncanonical amino acids or unnatural ones (UAAs), using a unique codon and a transfer-RNA:aminoacyl–tRNA-synthetase pair, in the frame-works of the proteins has yielded new horizons of chemistries, previously inaccessible in the presence of 20 naturally available amino acids. Since the development of site-specific incorporation of UAA through expression of recombinant proteins, a wide variety of non-canonical amino acids have been genetically encoded in prokaryotic and eukaryotic organisms. These UAAs can be utilized to explore new functional properties of the proteins, such as molecular probes and catalytic activities. Thus, a wide variety of physicochemical and biological properties of the proteins can be investigated using over 50 UAAs, which can be cotranslationally incorporated into proteins. Herein, a brief overview of the scope of genetic incorporation of UAA is presented, exhibiting their role in different a biological reaction.

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