Synthesis of polyester by means of genetic code reprogramming

Area of Science:

• Biochemistry
• Synthetic Biology
• Polymer Chemistry

Background:

• Ribosomes naturally synthesize proteins from amino acids.
• Genetic code reprogramming allows for the expansion of the natural amino acid repertoire.
• Alpha-hydroxy acids are monomers that can form polyesters, but their ribosomal synthesis is challenging.

Purpose of the Study:

• To achieve ribosomal polymerization of alpha-hydroxy acids.
• To demonstrate mRNA-directed synthesis of polyesters with defined sequences.
• To explore the potential of backbone-altered biopolymers.

Main Methods:

• Utilized the flexizyme system for tRNA acylation with alpha-hydroxy acids.
• Re-assigned codons to incorporate seven types of alpha-hydroxy acids into the genetic code.
• Employed a reconstituted cell-free translation system for polyester synthesis.
• Verified polyester sequence and length control via mRNA templates.

Main Results:

• Successfully achieved ribosomal synthesis of polyesters from alpha-hydroxy acids.
• Demonstrated high-fidelity control over polyester sequence and length using mRNA templates.
• Established a method for incorporating non-natural monomers into polymer backbones via ribosomes.

Conclusions:

• Genetic code reprogramming enables the synthesis of alpha-hydroxy acid-based polyesters.
• This approach allows for precise, mRNA-directed synthesis of backbone-altered biopolymers.
• Opens new avenues for creating novel biomaterials with tailored properties.