Dual Genetic Code System for Simultaneous Amino Acid Incorporation
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Solution Overview
Problem
Conventional genetic code reprogramming methods limit the simultaneous use of special and proteinogenic amino acids, as they require removing proteinogenic amino acids to assign special amino acids to vacant codons, restricting the diversity of peptides that can be synthesized.
Innovation Solution
The development of a dual genetic code system and artificial codon box division allows for the simultaneous use of 40 or more types of amino acids by creating dual sense codons and reassigning codons, enabling the use of all proteinogenic and special amino acids in peptide synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional genetic code reprogramming methods are used to assign special amino acids to vacant codons, then special amino acids can be incorporated into peptides, but proteinogenic amino acids must be removed from the system, limiting the diversity of amino acids that can be simultaneously used
Solution Approach 1:
The patent divides the 64 codons into multiple functional groups: initiation codons (AUG and alternative initiation codons), elongation codons (including divided codon boxes), and termination codons. This segmentation allows different codon groups to serve different functions simultaneously, enabling the system to incorporate both special and proteinogenic amino acids without conflict. Specifically, certain codon boxes are divided such that some codons assign special amino acids while others maintain proteinogenic amino acid assignments.
Solution Approach 2:
The patent creates a multi-functional genetic code system where codons serve multiple purposes: AUG functions as both an initiation codon and an elongation codon for methionine; alternative initiation codons (such as GUG, UUG) serve initiation functions while their corresponding codons in elongation maintain proteinogenic amino acid assignments. This multi-functionality maximizes the utilization of the 64 codons to support both special and proteinogenic amino acids simultaneously.
2Manufacturing precision
If the ribosomal translation apparatus is used for peptide synthesis, then precise sequence control of 20 proteinogenic amino acids is achieved, but peptides comprising special (non-standard) amino acids cannot be synthesized
Solution Approach 1:
The patent applies local quality by making specific modifications to particular codons and their corresponding tRNAs while maintaining the standard genetic code for other codons. Specifically, certain codon boxes are divided such that specific codons are reassigned to special amino acids with corresponding specialized tRNAs, while other codons maintain their standard proteinogenic amino acid assignments. This localized modification approach preserves the precision of the standard translation system for proteinogenic amino acids while enabling incorporation of special amino acids at specific positions.
Solution Approach 2:
The patent introduces dynamic flexibility to the genetic code system by allowing the same codon to have different functions depending on the translational context. For example, AUG serves as an initiation codon at the start of translation but as an elongation codon for methionine incorporation during peptide chain elongation. Alternative initiation codons similarly exhibit context-dependent functionality, enabling the system to adaptively control which amino acids are incorporated at different positions.
3Adaptability or versatility
If termination codons and 4 artificial base codons are used to assign 21st amino acids, then non-proteinogenic amino acids can be incorporated, but the number of simultaneous amino acid types is limited to a maximum of 3
Solution Approach 1:
The patent transitions from the traditional one-dimensional approach of simply replacing termination codons to a multi-dimensional utilization of the entire 64-codon space. By dividing codon boxes and creating alternative initiation codons in addition to modifying elongation codons, the system operates in multiple dimensions of codon functionality. This allows simultaneous assignment of special amino acids to multiple codon groups (initiation, elongation, and divided codon boxes) while preserving proteinogenic amino acid assignments in other codons, thereby dramatically increasing the total number of amino acid types that can be used.
Data Source
AI summary
A new artificial translation-synthesis system of adding tRNAs binding special amino acids to the in vitro translation system and synthesizing peptides with special amino acids incorporated thereto according to a dual genetic code table and an artificial codon box division.