Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?

Area of Science:

• Synthetic Biology (SB)
• Xenobiology (XB)
• Genetic Engineering
• Protein Engineering
• Proteome Engineering

Background:

• Synthetic biology (SB) focuses on creating biotechnologically applicable biodiversity.
• Xenobiology (XB) expands natural chemistry using non-natural building blocks for artificial biodiversity.
• Protein and proteome engineering overcome genetic code limitations by incorporating non-canonical amino acids (ncAAs).

Purpose of the Study:

• To explore the expansion of the genetic code with ncAAs for developing bio-containment mechanisms in synthetic cells.
• To engineer synthetic cells with a 'genetic firewall' (orthogonality) preventing genetic information transfer to natural systems.
• To identify biotechnological invasion points for engineering bio-contained synthetic cells with non-canonical functionalities.

Main Methods:

• Review and mapping of potential biotechnological invasion points for synthetic cell engineering.
• Consideration of the chemical logic behind amino acid repertoire establishment.
• Building upon proposals regarding genetic code establishment in the RNA world.

Main Results:

• Despite progress, complete alienation of organisms with permanently altered genetic codes remains challenging.
• The study maps potential strategies for introducing ncAAs and achieving orthogonality.
• Identified invasion points offer pathways for engineering synthetic cells with novel functionalities.

Conclusions:

• Engineering robust bio-contained life forms requires a deep understanding of amino acid repertoire establishment.
• Systematic introduction of ncAAs is crucial for achieving genetic firewall capabilities in synthetic cells.
• Further research into the chemical logic of genetic code expansion is needed for successful xenobiological applications.