Codon compression and novel codon creation for multiplex non-canonical amino acid incorporation.

Genetic code expansion enables multiplex noncanonical amino acid incorporation through codon compression and novel codon creation, expanding protein engineering capabilities.

• Why it matters: Current methods are limited to single-site modifications, restricting the development of complex, multifunctional proteins essential for advanced synthetic biology applications.
• What they did: The review analyzes two main strategies: natural codon compression via genome-wide recoding and the creation of new codons such as quadruplet codons and unnatural base pairs, assessing their efficiency and constraints.
• The result: Integrating partial codon compression, adaptive evolution, and AI-driven design offers a promising pathway to overcome existing barriers, enabling more sophisticated genetic encoding in diverse host organisms.