14TSB_SynBio: BaseHunter: a software tool for synthetic biology procurement

Proteins are encoded into DNA using four chemical bases (A, T, C and G). A string of three bases is called a codon. Since
DNA has four bases, a maximum of 64 (4x4x4) unique codons can be formed. Of the 64 possible codons, 61 are used to
encode amino acids. There only 20 different amino acids used to construct proteins. Rather than having unused codons,
life uses a system in which an average of three different codons encode the same amino acid. Consequently, the same
protein sequence can be encoded with many different DNA sequences. Each DNA sequence will vary with respect to
parameters such as translational efficiency, transcriptional efficiency, protein folding and ease of synthesis. Codon
optimisation is an algorithmic process that seeks to pick the best possible variant for a given purpose. The research part of
this project seeks to develop a way of measuring how well different codon optimisation algorithms perform. This will be
done by obtaining different codon optimised genes and measuring how they behave in living systems.

Proteins are encoded into DNA using four chemical bases (A, T, C and G). A string of three bases is called a codon. Since
DNA has four bases, a maximum of 64 (4x4x4) unique codons can be formed. Of the 64 possible codons, 61 are used to
encode amino acids. There only 20 different amino acids used to construct proteins. Rather than having unused codons,
life uses a system in which an average of three different codons encode the same amino acid. Consequently, the same
protein sequence can be encoded with many different DNA sequences. Each DNA sequence will vary with respect to
parameters such as translational efficiency, transcriptional efficiency, protein folding and ease of synthesis. Codon
optimisation is an algorithmic process that seeks to pick the best possible variant for a given purpose. The research part of
this project seeks to develop a way of measuring how well different codon optimisation algorithms perform. This will be
done by obtaining different codon optimised genes and measuring how they behave in living systems.

Gene synthesis prices are artificially elevated because they include the cost of associated services that vendors cannot sell
in isolation. This phenomenon is most commonly seen in the coupling of gene synthesis and codon optimisation services.
Almost every vendor claims to offer the very best codon optimisation service but in the absence of comparable
performance metrics these assertions have little real meaning. To tackle this problem, we will develop a standardised
experimental protocol for quantitatively measuring algorithm quality. The resulting characterisation data will be
disseminated through our online synthetic gene procurement tool. This output will enable gene synthesis and codon
optimisation services to be priced and marketed separately. This improved pricing model will accelerate the maturation of
both technologies. In addition, enabling researchers to rationally select codon optimisation services will lead to efficiency
savings in the 'design' stage of the synthetic biology engineering cycle.