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What is the reinterpretation of genetic code (residue-specific ncAA incorporation)?

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Final answer:

The reinterpretation of the genetic code involves methods such as amber codon suppression, rare sense codon reassignment, and quadruplet codons to incorporate non-canonical amino acids (NCAAs) into proteins, which could lead to the production of proteins with novel functionalities not currently available through conventional biosynthetic pathways.

Step-by-step explanation:

Reinterpretation of Genetic Code and ncAA Incorporation

The reinterpretation of the genetic code refers to advanced methods designed to incorporate non-canonical amino acids (NCAAs) into proteins, thereby extending the biochemical capabilities and functionalities of organisms. The incorporation of NCAAs into specific sites can be achieved through strategies such as amber codon suppression, rare sense codon reassignment, and the use of quadruplet codons. These methods have the potential to revolutionize the way proteins are created and used in biological systems, and they include applications in synthetic biology, pharmaceutical development, and the understanding of protein structure and function.

The site-specific incorporation methods involve either the mutation or knockout of the release factor, allowing orthogonal tRNAs to read through a specific stop or rare sense codon (e.g., amber stop codon UAG), or the engineering of a quadruplet codon, which is a four-base sequence recognized by a specially designed tRNA. These methods utilize orthogonal tRNA/synthetase pairs that have been specifically tailored to recognize the NCAA being introduced.

Proteome-wide reassignment expands the application by altering multiple codons across an organism's entire genome. This process provides greater flexibility in encoding NCAAs but entails more complex genetic and cellular engineering challenges, such as handling potential adverse effects on protein expression and function.

In summary, the incorporation of NCAAs into organisms through genetic code expansion provides a platform for new biological discoveries and applications. Advances in this field may lead to the creation of proteins with novel properties and functions that cannot be synthesized by traditional biological systems.

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