Multiple amino acid-excluded genetic codes for protein engineering using multiple sets of tRNA variants

Area of Science:

• Synthetic Biology
• Molecular Biology
• Biochemistry

Background:

• The universal genetic code assigns 20 amino acids to sense codons.
• Recent advancements introduced simplified genetic codes with fewer amino acid assignments.
• The potential for excluding multiple amino acids simultaneously remains largely unexplored.

Purpose of the Study:

• To develop novel simplified genetic codes by simultaneously excluding multiple amino acids from the universal code.
• To demonstrate a strategy for genetic code simplification applicable to various amino acid sets.
• To highlight the utility of simplified genetic codes in biotechnology and evolutionary studies.

Main Methods:

• Designing simplified genetic codes by reassigning codons for specific amino acids.
• Utilizing variants of transfer RNA (tRNA) to achieve novel amino acid assignments.
• Testing the exclusion of multiple amino acids, including tryptophan, cysteine, tyrosine, and asparagine, by reassigning their codons to serine.

Main Results:

• Successfully created simplified genetic codes with multiple amino acid exclusions.
• Demonstrated that tryptophan, cysteine, tyrosine, and asparagine codons can be reassigned to serine using four tRNA (Ser) variants.
• Confirmed the feasibility of excluding various sets of amino acids using the proposed strategy.

Conclusions:

• A versatile strategy exists for simplifying the genetic code by excluding multiple amino acids.
• Simplified genetic codes are powerful tools for protein engineering, enzyme improvement, and pharmaceutical development.
• These codes offer new perspectives for understanding protein evolution and the adaptability of genetic systems.